You are here

Wax, Adam P.

Overview:

Dr. Wax's research interests include optical spectroscopy for early cancer detection, novel microscopy and
interferometry techniques.


The study of intact, living cells with optical spectroscopy offers the opportunity to observe cellular structure, organization and dynamics in a way that is not possible with traditional methods. We have developed a set of novel spectroscopic techniques for measuring spatial, temporal and refractive structure on sub-hertz and sub-wavelength scales based on using low-coherence interferometry (LCI) to detect scattered light. We have applied these techniques in different types of cell biology experiments. In one experiment, LCI measurements of the angular pattern of backscattered light are used to determine non-invasively the structure of sub-cellular organelles in cell monolayers, and the components of epithelial tissue from freshly excised rat esophagus. This work has potential as a diagnostic method for early cancer detection. In another experiment, LCI phase measurements are used to examine volume changes of epithelial cells in a monolayer in response to environmental osmolarity changes. Although cell volume changes have been measured previously, this work demonstrates for the first time the volume of just a few cells (2 or 3) tracked continuously and in situ.

Positions:

Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Faculty Network Member of the Duke Institute for Brain Sciences

Duke Institute for Brain Sciences
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1993

B.S. — Rensselaer Polytechnic Institute

M.A. 1996

M.A. — Duke University

Ph.D. 1999

Ph.D. — Duke University

News:

Grants:

Advanced a/LCI systems for improved clinical utility

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 13, 2016
End Date
November 30, 2021

Training in Medical Imaging

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 15, 2003
End Date
August 31, 2019

Visualization of mechanical stress in live cells

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
July 01, 2016
End Date
June 30, 2019

Coherent light scattering for early detection of Alzheimer's disease

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 01, 2017
End Date
February 28, 2019

Novel Coherence Imaging to Evaluate the Health of the Cervical Epithelium

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 01, 2014
End Date
February 28, 2019

Improving Medical Outcomes Through Needle-Based Optical Sensing

Administered By
Biomedical Engineering
AwardedBy
North Carolina Biotechnology Center
Role
Principal Investigator
Start Date
August 20, 2015
End Date
August 19, 2017

Novel Determination of Microbicide PK in Women's Reproductive Health

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 15, 2012
End Date
March 31, 2017

EAGER: Cell phone enabled spectroscopy

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
August 01, 2014
End Date
July 31, 2016

Coherent light scattering for early detection of retinal disease

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 01, 2013
End Date
February 29, 2016

Inhibition of Reflux-Induced Esophageal Adenocarcinoma by Proanthocyanidins

Administered By
Biomedical Engineering
AwardedBy
Medical College of Wisconsin
Role
Principal Investigator
Start Date
April 30, 2013
End Date
January 31, 2016

InCh Microscope: Compact and Portable Quantitative Phase Microscope for Label-Free Morphological Diagnosis of Blood Samp

Administered By
Biomedical Engineering
AwardedBy
M2 Photonics Innovations
Role
Principal Investigator
Start Date
January 01, 2014
End Date
December 31, 2014

Increased Depth Penetration in Coherence Imaging Using Multiply Scattered Light

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
September 01, 2011
End Date
August 31, 2014

MRI: Development of a Hybrid Quantitative Phase Microscope for Live Cell Imaging

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
September 01, 2010
End Date
August 31, 2014

Cross-disciplinary Training in Medical Physics

Administered By
Duke University Medical Physics Graduate Program
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 2007
End Date
June 30, 2013

I-Corps: InCh holographic microscope for cell diagnostics

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
July 01, 2012
End Date
December 31, 2012

Coherence Imaging for Assessing Colorectal Neoplasia

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 24, 2009
End Date
April 30, 2012

Molecular Imaging Using Hyperspectral Darkfield Microscope of Nanoparticles

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
April 01, 2007
End Date
March 31, 2011

Assessing Deployment of Microbicidal Gels With Label-Free Optical Measurement

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2007
End Date
September 30, 2010

In Vivo Detection of Pre-Cancerous Lesions Using a /LCI

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2004
End Date
May 31, 2010

Low Coherence Light Scattering for Biophotonics

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
July 25, 2005
End Date
January 31, 2010

CAREER: Low Coherence Light Scattering for Biophotonics

Administered By
Biomedical Engineering
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
February 01, 2004
End Date
January 31, 2009

Assessing Nuclear Morphology in Thick Tissues Using fLCI

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 14, 2006
End Date
December 31, 2008

In Vivo Detection of Pre-Cancerous Lesions Using a/LCI

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2004
End Date
February 28, 2006
Show More

Awards:

Fellow. International Society for Optics and Photonics.

Type
National
Awarded By
International Society for Optics and Photonics
Date
January 01, 2010

Fellows. Optical Society of America.

Type
National
Awarded By
Optical Society of America
Date
January 01, 2010

Publications:

Roadmap for optofluidics

Authors
Minzioni, P; Osellame, R; Sada, C; Zhao, S; Omenetto, FG; Gylfason, KB; Haraldsson, T; Zhang, Y; Ozcan, A; Wax, A; Mugele, F; Schmidt, H; Testa, G; Bernini, R; Guck, J; Liberale, C; Berg-Sørensen, K; Chen, J; Pollnau, M; Xiong, S; Liu, A-Q; Shiue, C-C; Fan, S-K; Erickson, D; Sinton, D
MLA Citation
Minzioni, P, Osellame, R, Sada, C, Zhao, S, Omenetto, FG, Gylfason, KB, Haraldsson, T, Zhang, Y, Ozcan, A, Wax, A, Mugele, F, Schmidt, H, Testa, G, Bernini, R, Guck, J, Liberale, C, Berg-Sørensen, K, Chen, J, Pollnau, M, Xiong, S, Liu, A-Q, Shiue, C-C, Fan, S-K, Erickson, D, and Sinton, D. "Roadmap for optofluidics." Journal of Optics 19.9 (September 1, 2017): 093003-093003.
Source
crossref
Published In
Journal of Optics A: Pure and Applied Optics
Volume
19
Issue
9
Publish Date
2017
Start Page
093003
End Page
093003
DOI
10.1088/2040-8986/aa783b

Dual-axis optical coherence tomography for deep tissue imaging.

We have developed dual-axis optical coherence tomography (DA-OCT) which enables deep tissue imaging by using a novel off-axis illumination/detection configuration. DA-OCT offers a 100-fold speed increase compared with its predecessor, multispectral multiple-scattering low coherence interferometry (ms2/LCI), by using a new beam scanning mechanism based on a microelectro-mechanical system (MEMS) mirror. The data acquisition scheme was altered to take advantage of this scanning speed, producing tomographic images at a rate of 4 frames (B-scans) per second. DA-OCT differs from ms2/LCI in that the dual axes intersect at a shallower depth (∼1  mm). This difference, coupled with the faster scanning speed, shifts the detection priority from multiply scattered to ballistic light. The utility of this approach was demonstrated by imaging both ex vivo porcine ear skin and in vivo rat skin from a McFarlane flap model. The enhanced penetration depth provided by the DA-OCT system will be beneficial to various clinical applications in dermatology and surgery.

Authors
Zhao, Y; Eldridge, WJ; Maher, JR; Kim, S; Crose, M; Ibrahim, M; Levinson, H; Wax, A
MLA Citation
Zhao, Y, Eldridge, WJ, Maher, JR, Kim, S, Crose, M, Ibrahim, M, Levinson, H, and Wax, A. "Dual-axis optical coherence tomography for deep tissue imaging." Optics letters 42.12 (June 2017): 2302-2305.
PMID
28614337
Source
epmc
Published In
Optics Letters
Volume
42
Issue
12
Publish Date
2017
Start Page
2302
End Page
2305
DOI
10.1364/ol.42.002302

Refractive index tomography with structured illumination

Authors
Chowdhury, S; Eldridge, WJ; Wax, A; Izatt, J
MLA Citation
Chowdhury, S, Eldridge, WJ, Wax, A, and Izatt, J. "Refractive index tomography with structured illumination." Optica 4.5 (May 20, 2017): 537-537.
Source
crossref
Published In
Optica
Volume
4
Issue
5
Publish Date
2017
Start Page
537
End Page
537
DOI
10.1364/OPTICA.4.000537

Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy.

Sub-diffraction resolution imaging has played a pivotal role in biological research by visualizing key, but previously unresolvable, sub-cellular structures. Unfortunately, applications of far-field sub-diffraction resolution are currently divided between fluorescent and coherent-diffraction regimes, and a multimodal sub-diffraction technique that bridges this gap has not yet been demonstrated. Here we report that structured illumination (SI) allows multimodal sub-diffraction imaging of both coherent quantitative-phase (QP) and fluorescence. Due to SI's conventionally fluorescent applications, we first demonstrate the principle of SI-enabled three-dimensional (3D) QP sub-diffraction imaging with calibration microspheres. Image analysis confirmed enhanced lateral and axial resolutions over diffraction-limited QP imaging, and established striking parallels between coherent SI and conventional optical diffraction tomography. We next introduce an optical system utilizing SI to achieve 3D sub-diffraction, multimodal QP/fluorescent visualization of A549 biological cells fluorescently tagged for F-actin. Our results suggest that SI has a unique utility in studying biological phenomena with significant molecular, biophysical, and biochemical components.

Authors
Chowdhury, S; Eldridge, WJ; Wax, A; Izatt, JA
MLA Citation
Chowdhury, S, Eldridge, WJ, Wax, A, and Izatt, JA. "Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy." Biomedical optics express 8.5 (May 2017): 2496-2518.
PMID
28663887
Source
epmc
Published In
Biomedical Optics Express
Volume
8
Issue
5
Publish Date
2017
Start Page
2496
End Page
2518
DOI
10.1364/boe.8.002496

Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies.

The refractive index (RI) of biological materials is a fundamental parameter for the optical characterization of living systems. Numerous light scattering technologies are grounded in a quantitative knowledge of the refractive index at cellular and subcellular scales. Recent work in quantitative phase microscopy (QPM) has called into question the widely held assumption that the index of the cell nucleus is greater than that of the cytoplasm, a result which disagrees with much of the current literature. In this work, we critically examine the measurement of the nuclear and whole-cell refractive index using QPM, validating that nuclear refractive index is lower than that of cytoplasm in four diverse cell lines and their corresponding isolated nuclei. We further examine Mie scattering and phase-wrapping as potential sources of error in these measurements, finding they have minimal impact. Finally, we use simulation to examine the effects of incorrect RI assumptions on nuclear morphology measurements using angle-resolved scattering information. Despite an erroneous assumption of the nuclear refractive index, accurate measurement of nuclear morphology was maintained, suggesting that light scattering modalities remain effective.

Authors
Steelman, ZA; Eldridge, WJ; Weintraub, JB; Wax, A
MLA Citation
Steelman, ZA, Eldridge, WJ, Weintraub, JB, and Wax, A. "Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies." Journal of biophotonics (April 18, 2017).
PMID
28418104
Source
epmc
Published In
Journal of biophotonics
Publish Date
2017
DOI
10.1002/jbio.201600314

Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology.

This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001). Both processing techniques resulted in high sensitivity and specificity (>0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis.

Authors
Ho, D; Drake, TK; Smith-McCune, KK; Darragh, TM; Hwang, LY; Wax, A
MLA Citation
Ho, D, Drake, TK, Smith-McCune, KK, Darragh, TM, Hwang, LY, and Wax, A. "Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology." International journal of cancer 140.6 (March 2017): 1447-1456.
PMID
27883177
Source
epmc
Published In
International Journal of Cancer
Volume
140
Issue
6
Publish Date
2017
Start Page
1447
End Page
1456
DOI
10.1002/ijc.30539

Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy.

Confocal Raman spectroscopy was implemented in a new label-free technique to quantify molecular diffusion coefficients within gels. A leading anti-HIV drug, tenofovir, was analyzed in a clinical microbicide gel. The gel was tested undiluted, and in 10%-50% wt/wt dilutions with vaginal fluid simulant to capture the range of conditions likely occurring in vivo. The concentration distributions of tenofovir in gel over time and space were measured and input to a mathematical diffusion model to deduce diffusion coefficients. These were 3.16 ± 0.11 × 10-6 cm2/s in undiluted gel, and increased by 11%-46% depending on the extent of dilution. Results were interpreted with respect to traditional release rate measurements in devices such as Franz cells. This comparison highlighted an advantage of our assay in that it characterizes the diffusive barrier within the gel material itself; in contrast, release rate in the traditional assay is affected by external conditions, such as drug partitioning at the gel/liquid sink interface. This new assay is relevant to diffusion in polymeric hydrogels over pharmacologically relevant length scales, for example, those characteristic of topical drug delivery. Resulting transport parameters are salient measures of drug delivery potential, and serve as inputs to computational models of drug delivery performance.

Authors
Chuchuen, O; Maher, JR; Simons, MG; Peters, JJ; Wax, AP; Katz, DF
MLA Citation
Chuchuen, O, Maher, JR, Simons, MG, Peters, JJ, Wax, AP, and Katz, DF. "Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy." Journal of pharmaceutical sciences 106.2 (February 2017): 639-644.
PMID
27837968
Source
epmc
Published In
Journal of Pharmaceutical Sciences
Volume
106
Issue
2
Publish Date
2017
Start Page
639
End Page
644
DOI
10.1016/j.xphs.2016.09.030

Optical Phase Measurements of Disorder Strength Link Microstructure to Cell Stiffness.

There have been sustained efforts on the part of cell biologists to understand the mechanisms by which cells respond to mechanical stimuli. To this end, many rheological tools have been developed to characterize cellular stiffness. However, measurement of cellular viscoelastic properties has been limited in scope by the nature of most microrheological methods, which require direct mechanical contact, applied at the single-cell level. In this article, we describe, to our knowledge, a new analysis approach for quantitative phase imaging that relates refractive index variance to disorder strength, a parameter that is linked to cell stiffness. Significantly, both disorder strength and cell stiffness are measured with the same phase imaging system, presenting a unique alternative for label-free, noncontact, single-shot imaging of cellular rheologic properties. To demonstrate the potential applicability of the technique, we measure phase disorder strength and shear stiffness across five cellular populations with varying mechanical properties and demonstrate an inverse relationship between these two parameters. The existence of this relationship suggests that predictions of cell mechanical properties can be obtained from examining the disorder strength of cell structure using this, to our knowledge, novel, noncontact technique.

Authors
Eldridge, WJ; Steelman, ZA; Loomis, B; Wax, A
MLA Citation
Eldridge, WJ, Steelman, ZA, Loomis, B, and Wax, A. "Optical Phase Measurements of Disorder Strength Link Microstructure to Cell Stiffness." Biophysical Journal 112.4 (February 2017): 692-702.
PMID
28256229
Source
epmc
Published In
Biophysical Journal
Volume
112
Issue
4
Publish Date
2017
Start Page
692
End Page
702
DOI
10.1016/j.bpj.2016.12.016

In vivo rat skin flap viability assessment using dual axis spectroscopic optical coherence tomography

© 2017 OSA. Dual Axis (DA) spectroscopic optical coherence tomography enables deep tissue imaging and provides diagnostic information. Here it is applied to a McFarlane rat flap model, which exhibits a gradient in tissue injury along the flap length.

Authors
Zhao, Y; Maher, JR; Ibrahim, MM; Chien, JS; Levinson, H; Wax, A
MLA Citation
Zhao, Y, Maher, JR, Ibrahim, MM, Chien, JS, Levinson, H, and Wax, A. "In vivo rat skin flap viability assessment using dual axis spectroscopic optical coherence tomography." January 1, 2017.
Source
scopus
Published In
Optics InfoBase Conference Papers
Volume
Part F62-BODA 2017
Publish Date
2017
DOI
10.1364/BODA.2017.BoM4A.4

Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography.

Vaginally applied microbicide products offer a female-controlled strategy for preventing sexual transmission of HIV. Microbicide transport processes are central to their functioning, and there is a clear need for a better understanding of them. To contribute to that end, we developed an assay to analyze mass transport rates of microbicide molecules within the epithelial and stromal layers of polarized vaginal mucosal tissue during contact with a gel vehicle. The assay utilizes a new diffusion chamber mounted in a custom instrument that combines confocal Raman spectroscopy and optical coherence tomography. This measures depth-resolved microbicide concentration distributions within epithelium and stroma. Data for a tenofovir gel were fitted with a compartmental diffusion model to obtain fundamental transport properties: the molecular diffusion and partition coefficients in different compartments. Diffusion coefficients in epithelium and stroma were computed to be 6.10 ± 2.12 x 10-8 and 4.52 ± 1.86 x 10-7 cm2/sec, respectively. The partition coefficients between epithelium and gel and between stroma and epithelium were found to be 0.53 ± 0.15 and 1.17 ± 0.16, respectively. These drug transport parameters are salient in governing the drug delivery performance of different drug and gel vehicle systems. They can be used to contrast drugs and vehicles during product design, development and screening. They are critical inputs to deterministic transport models that predict the gels' pharmacokinetic performance, which can guide improved design of products and optimization of their dosing regimens.

Authors
Chuchuen, O; Maher, JR; Henderson, MH; Desoto, M; Rohan, LC; Wax, A; Katz, DF
MLA Citation
Chuchuen, O, Maher, JR, Henderson, MH, Desoto, M, Rohan, LC, Wax, A, and Katz, DF. "Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography." PloS one 12.9 (January 2017): e0185633-.
PMID
28961280
Source
epmc
Published In
PloS one
Volume
12
Issue
9
Publish Date
2017
Start Page
e0185633
DOI
10.1371/journal.pone.0185633

Deep imaging of absorption and scattering features by multispectral multiple scattering low coherence interferometry.

We have developed frequency domain multispectral multiple scattering low coherence interferometry (ms2/LCI) for deep imaging of absorption and scattering contrast. Using tissue-mimicking phantoms that match the full scattering phase function of human dermal tissue, we demonstrate that ms2/LCI can provide a signal/noise ratio (SNR) improvement of 15.4 dB over conventional OCT at an imaging depth of 1 mm. The enhanced SNR and penetration depth provided by ms2/LCI could be leveraged for a variety of clinical applications including the assessment of burn injuries where current clinical classification of severity only provides limited accuracy. The utility of the approach was demonstrated by imaging a tissue phantom simulating a partial-thickness burn revealing good spectroscopic contrast between healthy and injured tissue regions deep below the sample surface. Finally, healthy rat skin was imaged in vivo with both a commercial OCT instrument and our custom ms2/LCI system. The results demonstrate that ms2/LCI is capable of obtaining spectroscopic information far beyond the penetration depth provided by conventional OCT.

Authors
Zhao, Y; Maher, JR; Ibrahim, MM; Chien, JS; Levinson, H; Wax, A
MLA Citation
Zhao, Y, Maher, JR, Ibrahim, MM, Chien, JS, Levinson, H, and Wax, A. "Deep imaging of absorption and scattering features by multispectral multiple scattering low coherence interferometry." Biomedical optics express 7.10 (October 2016): 3916-3926.
PMID
27867703
Source
epmc
Published In
Biomedical Optics Express
Volume
7
Issue
10
Publish Date
2016
Start Page
3916
End Page
3926
DOI
10.1364/boe.7.003916

Found in translation: Biophotonics from lab to clinic

Authors
Wax, A; Chu, K
MLA Citation
Wax, A, and Chu, K. "Found in translation: Biophotonics from lab to clinic." Optics and Photonics News 27.9 (September 1, 2016): 34-41.
Source
scopus
Published In
Optics & Photonics News
Volume
27
Issue
9
Publish Date
2016
Start Page
34
End Page
41

Hemoglobin consumption by P. falciparum in individual erythrocytes imaged via quantitative phase spectroscopy.

Plasmodium falciparum infection causes structural and biochemical changes in red blood cells (RBCs). To quantify these changes, we apply a novel optical technique, quantitative phase spectroscopy (QPS) to characterize individual red blood cells (RBCs) during the intraerythrocytic life cycle of P. falciparum. QPS captures hyperspectral holograms of individual RBCs to measure spectroscopic changes across the visible wavelength range (475-700 nm), providing complex information, i.e. amplitude and phase, about the light field which has interacted with the cell. The complex field provides complimentary information on hemoglobin content and cell mass, which are both found to dramatically change upon infection by P. falciparum. Hb content progressively decreases with parasite life cycle, with an average 72.2% reduction observed for RBCs infected by schizont-stage P. falciparum compared to uninfected cells. Infection also resulted in a 33.1% reduction in RBC's optical volume, a measure of the cells' non-aqueous components. Notably, optical volume is only partially correlated with hemoglobin content, suggesting that changes in other dry mass components such as parasite mass may also be assessed using this technique. The unique ability of QPS to discriminate individual healthy and infected cells using spectroscopic changes indicates that the approach can be used to detect disease.

Authors
Rinehart, MT; Park, HS; Walzer, KA; Chi, J-TA; Wax, A
MLA Citation
Rinehart, MT, Park, HS, Walzer, KA, Chi, J-TA, and Wax, A. "Hemoglobin consumption by P. falciparum in individual erythrocytes imaged via quantitative phase spectroscopy." Scientific reports 6 (April 18, 2016): 24461-.
PMID
27087557
Source
epmc
Published In
Scientific Reports
Volume
6
Publish Date
2016
Start Page
24461
DOI
10.1038/srep24461

Toward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometryToward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometry

© OSA 2016. Oxygenation of hemolyzed blood was measured with multispectral multiple-scattering low coherence interferometry revealing a high correlation (r 2 =0.961) with gold-standard spectrophotometer measurements.

Authors
Zhao, Y; Maher, JR; Wax, A; Zhao, Y; Maher, JR; Wax, A
MLA Citation
Zhao, Y, Maher, JR, Wax, A, Zhao, Y, Maher, JR, and Wax, A. "Toward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometryToward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometry (PublishedPublished)." April 18, 2016.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2016
DOI
10.1364/TRANSLATIONAL.2016.JM3A.24

Guidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissueGuidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissue

© OSA 2016. Here we present the analysis of two dimensional angle-resolved low coherence interferometry (2D a/LCI) measurements co-registered with optical coherence tomography (OCT) imaging to guide the a/LCI measurements on an esophageal cancer rat model.

Authors
Kim, S; Crose, M; Kresty, LA; Wax, A; Kim, S; Crose, M; Kresty, LA; Wax, A
MLA Citation
Kim, S, Crose, M, Kresty, LA, Wax, A, Kim, S, Crose, M, Kresty, LA, and Wax, A. "Guidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissueGuidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissue (PublishedPublished)." April 18, 2016.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2016
DOI
10.1364/TRANSLATIONAL.2016.JTu3A.16

Guidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissue

© OSA 2016. Here we present the analysis of two dimensional angle-resolved low coherence interferometry (2D a/LCI) measurements co-registered with optical coherence tomography (OCT) imaging to guide the a/LCI measurements on an esophageal cancer rat model.

Authors
Kim, S; Crose, M; Kresty, LA; Wax, A
MLA Citation
Kim, S, Crose, M, Kresty, LA, and Wax, A. "Guidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissue." April 18, 2016.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2016
Start Page
3

Toward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometry

© OSA 2016. Oxygenation of hemolyzed blood was measured with multispectral multiple-scattering low coherence interferometry revealing a high correlation (r 2 =0.961) with gold-standard spectrophotometer measurements.

Authors
Zhao, Y; Maher, JR; Wax, A
MLA Citation
Zhao, Y, Maher, JR, and Wax, A. "Toward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometry." April 18, 2016.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2016
Start Page
3

Analyzing spatial correlations in tissue using angle-resolved low coherence interferometry measurements guided by co-located optical coherence tomography.

Angle-resolved low coherence interferometry (a/LCI) is an optical technique used to measure nuclear morphology in situ. However, a/LCI is not an imaging modality and can produce ambiguous results when the measurements are not properly oriented to the tissue architecture. Here we present a 2D a/LCI system which incorporates optical coherence tomography imaging to guide the measurements. System design and characterization are presented, along with example cases which demonstrate the utility of the combined measurements. In addition, future development and applications of this dual modality approach are discussed.

Authors
Kim, S; Heflin, S; Kresty, LA; Halling, M; Perez, LN; Ho, D; Crose, M; Brown, W; Farsiu, S; Arshavsky, V; Wax, A
MLA Citation
Kim, S, Heflin, S, Kresty, LA, Halling, M, Perez, LN, Ho, D, Crose, M, Brown, W, Farsiu, S, Arshavsky, V, and Wax, A. "Analyzing spatial correlations in tissue using angle-resolved low coherence interferometry measurements guided by co-located optical coherence tomography." Biomedical optics express 7.4 (April 2016): 1400-1414.
PMID
27446664
Source
epmc
Published In
Biomedical Optics Express
Volume
7
Issue
4
Publish Date
2016
Start Page
1400
End Page
1414
DOI
10.1364/boe.7.001400

Imaging deformation of adherent cells due to shear stress using quantitative phase imaging.

We present a platform for detecting cellular deformations from mechanical stimuli, such as fluid shear stress, using rapid quantitative phase imaging. Rapid quantitative phase imaging was used to analyze changes in the optical path length of adherent skin cancer cells during mechanical displacement. Both the whole-cell phase displacement and the resultant shift of the cellular center of mass were calculated over the duration of the stimulus. Whole-cell phase displacement images were found to match expectation. Furthermore, center-of-mass shifts of adherent cells were found to resemble that of a one-dimensional Kelvin-Voigt (KV) viscoelastic solid. Cellular steady-state displacements from step fluid shear stimuli were found to be linearly related to the shear stress. Shear stiffness constants for cells exposed to a cytoskeletal disrupting toxin were found to be significantly lower than unexposed cells. This novel technique allows for elastographic analysis of whole-cell effective shear stiffness without the use of an exogenous force applicator, a specialized culture substrate, or tracking net perimeter movement of the cell.

Authors
Eldridge, WJ; Sheinfeld, A; Rinehart, MT; Wax, A
MLA Citation
Eldridge, WJ, Sheinfeld, A, Rinehart, MT, and Wax, A. "Imaging deformation of adherent cells due to shear stress using quantitative phase imaging." Optics letters 41.2 (January 2016): 352-355.
PMID
26766712
Source
epmc
Published In
Optics Letters
Volume
41
Issue
2
Publish Date
2016
Start Page
352
End Page
355
DOI
10.1364/ol.41.000352

Automated Detection of P. falciparum Using Machine Learning Algorithms with Quantitative Phase Images of Unstained Cells.

Malaria detection through microscopic examination of stained blood smears is a diagnostic challenge that heavily relies on the expertise of trained microscopists. This paper presents an automated analysis method for detection and staging of red blood cells infected by the malaria parasite Plasmodium falciparum at trophozoite or schizont stage. Unlike previous efforts in this area, this study uses quantitative phase images of unstained cells. Erythrocytes are automatically segmented using thresholds of optical phase and refocused to enable quantitative comparison of phase images. Refocused images are analyzed to extract 23 morphological descriptors based on the phase information. While all individual descriptors are highly statistically different between infected and uninfected cells, each descriptor does not enable separation of populations at a level satisfactory for clinical utility. To improve the diagnostic capacity, we applied various machine learning techniques, including linear discriminant classification (LDC), logistic regression (LR), and k-nearest neighbor classification (NNC), to formulate algorithms that combine all of the calculated physical parameters to distinguish cells more effectively. Results show that LDC provides the highest accuracy of up to 99.7% in detecting schizont stage infected cells compared to uninfected RBCs. NNC showed slightly better accuracy (99.5%) than either LDC (99.0%) or LR (99.1%) for discriminating late trophozoites from uninfected RBCs. However, for early trophozoites, LDC produced the best accuracy of 98%. Discrimination of infection stage was less accurate, producing high specificity (99.8%) but only 45.0%-66.8% sensitivity with early trophozoites most often mistaken for late trophozoite or schizont stage and late trophozoite and schizont stage most often confused for each other. Overall, this methodology points to a significant clinical potential of using quantitative phase imaging to detect and stage malaria infection without staining or expert analysis.

Authors
Park, HS; Rinehart, MT; Walzer, KA; Chi, J-TA; Wax, A
MLA Citation
Park, HS, Rinehart, MT, Walzer, KA, Chi, J-TA, and Wax, A. "Automated Detection of P. falciparum Using Machine Learning Algorithms with Quantitative Phase Images of Unstained Cells." PloS one 11.9 (January 2016): e0163045-.
PMID
27636719
Source
epmc
Published In
PloS one
Volume
11
Issue
9
Publish Date
2016
Start Page
e0163045
DOI
10.1371/journal.pone.0163045

Spatial frequency-domain multiplexed microscopy for simultaneous, single-camera, one-shot, fluorescent, and quantitative-phase imaging.

Multimodal imaging is a crucial tool when imaging biological phenomena that cannot be comprehensively captured by a single modality. Here, we introduce a theoretical framework for spatial-frequency-multiplexed microscopy via off-axis interference as a novel wide-field imaging technique that enables true simultaneous multimodal and multichannel wide-field imaging. We experimentally demonstrate this technique for single-camera, simultaneous two-channel fluorescence and one-channel quantitative-phase imaging for fluorescent microspheres and fixed cells stained for F-actin and nuclear fluorescence.

Authors
Chowdhury, S; Eldridge, WJ; Wax, A; Izatt, JA
MLA Citation
Chowdhury, S, Eldridge, WJ, Wax, A, and Izatt, JA. "Spatial frequency-domain multiplexed microscopy for simultaneous, single-camera, one-shot, fluorescent, and quantitative-phase imaging." Optics letters 40.21 (November 2015): 4839-4842.
PMID
26512463
Source
epmc
Published In
Optics Letters
Volume
40
Issue
21
Publish Date
2015
Start Page
4839
End Page
4842
DOI
10.1364/ol.40.004839

Evaluation of burn severity in vivo in a mouse model using spectroscopic optical coherence tomography.

Clinical management of burn injuries depends upon an accurate assessment of the depth of the wound. Current diagnostic methods rely primarily on subjective visual inspection, which can produce variable results. In this study, spectroscopic optical coherence tomography was used to objectively evaluate burn injuries in vivo in a mouse model. Significant spectral differences were observed and correlated with the depth of the injury as determined by histopathology. The relevance of these results to clinical burn management in human tissues is discussed.

Authors
Zhao, Y; Maher, JR; Kim, J; Selim, MA; Levinson, H; Wax, A
MLA Citation
Zhao, Y, Maher, JR, Kim, J, Selim, MA, Levinson, H, and Wax, A. "Evaluation of burn severity in vivo in a mouse model using spectroscopic optical coherence tomography." Biomedical optics express 6.9 (September 2015): 3339-3345.
PMID
26417505
Source
epmc
Published In
Biomedical Optics Express
Volume
6
Issue
9
Publish Date
2015
Start Page
3339
End Page
3345
DOI
10.1364/boe.6.003339

Molecular contrast in interferometric imaging

© 2015 OSA. Interferometric imaging offers many advantages for biomedical applications such as optical sectioning/depth resolution. Inclusion of molecular contrast information improves utility but requires additional efforts to either isolate spectroscopic information or detect contrast agents.

Authors
Wax, A
MLA Citation
Wax, A. "Molecular contrast in interferometric imaging." August 10, 2015.
Source
scopus
Published In
Conference on Lasers and Electro-Optics Europe - Technical Digest
Volume
2015-August
Publish Date
2015

Quantitative phase imaging with molecular sensitivity using photoacoustic microscopy with a miniature ring transducer.

We present a dual-modality system for both structural and molecular cell imaging based on coregistered quantitative phase imaging (QPI) and photoacoustic microscopy (PAM). The QPI system was based on off-axis holography, whereas the PAM system comprised a sinusoidally modulated optical source for excitation and a narrow-band low profile and low-cost ring ultrasonic transducer for detection. This approach facilitated a simple confocal alignment of the excitation beams of both modalities and the ultrasonic detector. This system was demonstrated by imaging endogenous molecules in red blood cells (RBCs) as well as by imaging exogenous molecular labels on cancer cells using gold nanoparticles (GNPs) functionalized to target epidermal growth factor receptor. QPI provided high resolution imaging of the cellular structures while PAM provided molecular contrast. This dual-modality microscopy method can potentially be implemented as a compact and low cost cellular diagnostic assay.

Authors
Sheinfeld, A; Eldridge, WJ; Wax, A
MLA Citation
Sheinfeld, A, Eldridge, WJ, and Wax, A. "Quantitative phase imaging with molecular sensitivity using photoacoustic microscopy with a miniature ring transducer." Journal of biomedical optics 20.8 (August 2015): 86002-.
PMID
26263416
Source
epmc
Published In
Journal of Biomedical Optics
Volume
20
Issue
8
Publish Date
2015
Start Page
86002
DOI
10.1117/1.jbo.20.8.086002

Evaluation of hybrid algorithm for analysis of scattered light using ex vivo nuclear morphology measurements of cervical epithelium.

We evaluate a new hybrid algorithm for determining nuclear morphology using angle-resolved low coherence interferometry (a/LCI) measurements in ex vivo cervical tissue. The algorithm combines Mie theory based and continuous wavelet transform inverse light scattering analysis. The hybrid algorithm was validated and compared to traditional Mie theory based analysis using an ex vivo tissue data set. The hybrid algorithm achieved 100% agreement with pathology in distinguishing dysplastic and non-dysplastic biopsy sites in the pilot study. Significantly, the new algorithm performed over four times faster than traditional Mie theory based analysis.

Authors
Ho, D; Drake, TK; Bentley, RC; Valea, FA; Wax, A
MLA Citation
Ho, D, Drake, TK, Bentley, RC, Valea, FA, and Wax, A. "Evaluation of hybrid algorithm for analysis of scattered light using ex vivo nuclear morphology measurements of cervical epithelium." Biomedical optics express 6.8 (August 2015): 2755-2765.
PMID
26309741
Source
epmc
Published In
Biomedical Optics Express
Volume
6
Issue
8
Publish Date
2015
Start Page
2755
End Page
2765
DOI
10.1364/boe.6.002755

Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue.

We report the development of a combined confocal Raman spectroscopy (CRS) and optical coherence tomography (OCT) instrument (CRS-OCT) capable of measuring analytes in targeted biological tissues with sub-100-micron spatial resolution. The OCT subsystem was used to measure depth-resolved tissue morphology and guide the acquisition of chemically-specific Raman spectra. To demonstrate its utility, the instrument was used to accurately measure depth-resolved, physiologically-relevant concentrations of Tenofovir, a microbicide drug used to prevent the sexual transmission of HIV, in ex vivo tissue samples.

Authors
Maher, JR; Chuchuen, O; Henderson, MH; Kim, S; Rinehart, MT; Kashuba, ADM; Wax, A; Katz, DF
MLA Citation
Maher, JR, Chuchuen, O, Henderson, MH, Kim, S, Rinehart, MT, Kashuba, ADM, Wax, A, and Katz, DF. "Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue." Biomedical optics express 6.6 (June 2015): 2022-2035.
PMID
26114026
Source
epmc
Published In
Biomedical Optics Express
Volume
6
Issue
6
Publish Date
2015
Start Page
2022
End Page
2035
DOI
10.1364/boe.6.002022

Influence of defocus on quantitative analysis of microscopic objects and individual cells with digital holography.

Digital holography offers a unique method for studying microscopic objects using quantitative measurements of the optical phase delays of transmitted light. The optical phase may be integrated across the object to produce an optical volume measurement, a parameter related to dry mass by a simple scaling factor. While digital holography is useful for comparing the properties of microscopic objects, especially cells, we show here that quantitative comparisons of optical phase can be influenced by the focal plane of the measurement. Although holographic images can be refocused digitally using Fresnel propagation, ambiguity can result if this aspect is not carefully controlled. We demonstrate that microscopic objects can be accurately profiled by employing a digital refocusing method to analyze phase profiles of polystyrene microspheres and red blood cells.

Authors
Rinehart, MT; Park, HS; Wax, A
MLA Citation
Rinehart, MT, Park, HS, and Wax, A. "Influence of defocus on quantitative analysis of microscopic objects and individual cells with digital holography." Biomedical optics express 6.6 (June 2015): 2067-2075.
PMID
26114029
Source
epmc
Published In
Biomedical Optics Express
Volume
6
Issue
6
Publish Date
2015
Start Page
2067
End Page
2075
DOI
10.1364/boe.6.002067

Functional optical coherence tomography: principles and progress.

In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues. This review emphasizes the newer techniques of SOCT and molecular imaging OCT, which show excellent potential for clinical application but have yet to be well reviewed in the literature. SOCT elucidates tissue characteristics, such as oxygenation and carcinogenesis, by detecting wavelength-dependent absorption and scattering of light in tissues. While SOCT measures endogenous biochemical distributions, molecular imaging OCT detects exogenous molecular contrast agents. These newer advances in functional OCT broaden the potential clinical application of OCT by providing novel ways to understand tissue activity that cannot be accomplished by other current imaging methodologies.

Authors
Kim, J; Brown, W; Maher, JR; Levinson, H; Wax, A
MLA Citation
Kim, J, Brown, W, Maher, JR, Levinson, H, and Wax, A. "Functional optical coherence tomography: principles and progress." Physics in medicine and biology 60.10 (May 8, 2015): R211-R237. (Review)
PMID
25951836
Source
epmc
Published In
Physics in Medicine and Biology
Volume
60
Issue
10
Publish Date
2015
Start Page
R211
End Page
R237
DOI
10.1088/0031-9155/60/10/r211

Elastic scattering spectroscopy and optical coherence tomography

© Springer-Verlag Berlin Heidelberg 2008 and Springer International Publishing Switzerland 2015. Elastically scattered light contains information about the scattering medium with which it has interacted. The elastic scattering process can be interpreted as a change in the momentum of light due to its interaction with a scattering object. By analyzing this change in momentum, structural information such as the size, shape, and organization of scattering objects can be recovered. Recently, light–scattering techniques have been developed for examining biological cells and tissues both in the laboratory and the clinic. These techniques are broadly termed elastic scattering spectroscopy (ESS).

Authors
Wax, A; Giacomelli, M; Robles, F
MLA Citation
Wax, A, Giacomelli, M, and Robles, F. "Elastic scattering spectroscopy and optical coherence tomography." Optical Coherence Tomography: Technology and Applications, Second Edition. January 1, 2015. 1207-1235.
Source
scopus
Publish Date
2015
Start Page
1207
End Page
1235
DOI
10.1007/978-3-319-06419-2_38

Noise characterization of supercontinuum sources for low-coherence interferometry applications.

We examine the noise properties of supercontinuum light sources when used in low-coherence interferometry applications. The first application is a multiple-scattering low-coherence interferometry (ms2/LCI) system, where high power and long image acquisition times are required to image deep into tissue. For this system, we compare the noise characteristics of two supercontinuum sources from different suppliers. Both sources have long-term drift that limits the amount of time over which signal averaging is advantageous for reducing noise. The second application is a high-resolution optical coherence tomography system, where broadband light is needed for high axial resolution. For this system, we compare the noise performance of the two supercontinuum sources and a light source based on four superluminescent diodes (SLD) using imaging contrast as a comparative metric. We find that the NKT SuperK has superior noise performance compared with the Fianium SC-450-4, but neither meets the performance of the SLD.

Authors
Brown, WJ; Kim, S; Wax, A
MLA Citation
Brown, WJ, Kim, S, and Wax, A. "Noise characterization of supercontinuum sources for low-coherence interferometry applications." Journal of the Optical Society of America. A, Optics, image science, and vision 31.12 (December 2014): 2703-2710.
PMID
25606759
Source
epmc
Published In
Journal of the Optical Society of America A
Volume
31
Issue
12
Publish Date
2014
Start Page
2703
End Page
2710
DOI
10.1364/josaa.31.002703

In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography.

Spectroscopic analysis of biological tissues can provide insight into changes in structure and function due to disease or injury. Depth-resolved spectroscopic measurements can be implemented for tissue imaging using optical coherence tomography (OCT). Here, spectroscopic OCT is applied to in vivo measurement of burn injury in a mouse model. Data processing and analysis methods are compared for their accuracy. Overall accuracy in classifying burned tissue was found to be as high as 91%, producing an area under the curve of a receiver operating characteristic curve of 0.97. The origins of the spectral changes are identified by correlation with histopathology.

Authors
Maher, JR; Jaedicke, V; Medina, M; Levinson, H; Selim, MA; Brown, WJ; Wax, A
MLA Citation
Maher, JR, Jaedicke, V, Medina, M, Levinson, H, Selim, MA, Brown, WJ, and Wax, A. "In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography." Optics letters 39.19 (October 2014): 5594-5597.
PMID
25360936
Source
epmc
Published In
Optics Letters
Volume
39
Issue
19
Publish Date
2014
Start Page
5594
End Page
5597
DOI
10.1364/ol.39.005594

Wavelet transform fast inverse light scattering analysis for size determination of spherical scatterers.

We present a fast approach for size determination of spherical scatterers using the continuous wavelet transform of the angular light scattering profile to address the computational limitations of previously developed sizing techniques. The potential accuracy, speed, and robustness of the algorithm were determined in simulated models of scattering by polystyrene beads and cells. The algorithm was tested experimentally on angular light scattering data from polystyrene bead phantoms and MCF-7 breast cancer cells using a 2D a/LCI system. Theoretical sizing of simulated profiles of beads and cells produced strong fits between calculated and actual size (r(2) = 0.9969 and r(2) = 0.9979 respectively), and experimental size determinations were accurate to within one micron.

Authors
Ho, D; Kim, S; Drake, TK; Eldridge, WJ; Wax, A
MLA Citation
Ho, D, Kim, S, Drake, TK, Eldridge, WJ, and Wax, A. "Wavelet transform fast inverse light scattering analysis for size determination of spherical scatterers." Biomedical optics express 5.10 (October 2014): 3292-3304.
PMID
25360350
Source
epmc
Published In
Biomedical Optics Express
Volume
5
Issue
10
Publish Date
2014
Start Page
3292
End Page
3304
DOI
10.1364/boe.5.003292

Deep tissue imaging using spectroscopic analysis of multiply scattered light

Authors
Matthews, TE; Medina, M; Maher, JR; Levinson, H; Brown, WJ; Wax, A
MLA Citation
Matthews, TE, Medina, M, Maher, JR, Levinson, H, Brown, WJ, and Wax, A. "Deep tissue imaging using spectroscopic analysis of multiply scattered light." Optica 1.2 (August 20, 2014): 105-105.
Source
crossref
Published In
Optica
Volume
1
Issue
2
Publish Date
2014
Start Page
105
End Page
105
DOI
10.1364/OPTICA.1.000105

Fast wide-field photothermal and quantitative phase cell imaging with optical lock-in detection.

We present a fast, wide-field holography system for detecting photothermally excited gold nanospheres with combined quantitative phase imaging. An interferometric photothermal optical lock-in approach (POLI) is shown to improve SNR for detecting nanoparticles (NPs) on multiple substrates, including a monolayer of NPs on a silanized coverslip, and NPs bound to live cells. Furthermore, the set up allowed for co-registered quantitative phase imaging (QPI) to be acquired in an off-axis holographic set-up. An SNR of 103 was obtained for NP-tagging of epidermal growth factor receptor (EGFR) in live cells with a 3 second acquisition, while an SNR of 47 was seen for 20 ms acquisition. An analysis of improvements in SNR due to averaging multiple frames is presented, which suggest that residual photothermal signal can be a limiting factor. The combination of techniques allows for high resolution imaging of cell structure via QPI with the ability to identify receptor expression via POLI.

Authors
Eldridge, WJ; Meiri, A; Sheinfeld, A; Rinehart, MT; Wax, A
MLA Citation
Eldridge, WJ, Meiri, A, Sheinfeld, A, Rinehart, MT, and Wax, A. "Fast wide-field photothermal and quantitative phase cell imaging with optical lock-in detection." Biomedical optics express 5.8 (August 2014): 2517-2525.
PMID
25136482
Source
epmc
Published In
Biomedical Optics Express
Volume
5
Issue
8
Publish Date
2014
Start Page
2517
End Page
2525
DOI
10.1364/boe.5.002517

Corruption of refractive index measurements of spheres using quantitative phase microscopyCorruption of refractive index measurements of spheres using quantitative phase microscopy

© OSA 2016. Recent Quantitative Phase Microscopy experiments have measured the refractive index of a cell nucleus to be lower than the cytoplasm. We suggest a potential error capable of corrupting these measurements.

Authors
Steelman, ZA; Eldridge, WJ; Park, HS; Wax, A; Steelman, ZA; Eldridge, WJ; Park, HS; Wax, A
MLA Citation
Steelman, ZA, Eldridge, WJ, Park, HS, Wax, A, Steelman, ZA, Eldridge, WJ, Park, HS, and Wax, A. "Corruption of refractive index measurements of spheres using quantitative phase microscopyCorruption of refractive index measurements of spheres using quantitative phase microscopy (PublishedPublished)." July 21, 2014.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2014
DOI
10.1364/FIO.2016.JTh2A.126

Toward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometryToward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometry

© OSA 2016. Oxygenation of hemolyzed blood was measured with multispectral multiple-scattering low coherence interferometry revealing a high correlation (r 2 =0.961) with gold-standard spectrophotometer measurements.

Authors
Zhao, Y; Maher, JR; Wax, A; Zhao, Y; Maher, JR; Wax, A
MLA Citation
Zhao, Y, Maher, JR, Wax, A, Zhao, Y, Maher, JR, and Wax, A. "Toward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometryToward the assessment of blood oxygenation using multispectral multiple scattering low coherence interferometry (PublishedPublished)." July 21, 2014.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2014
DOI
10.1364/CANCER.2016.JM3A.24

Linking cellular disorder strength and shear stiffness using quantitative phase imagingLinking cellular disorder strength and shear stiffness using quantitative phase imaging

© OSA 2016. Quantitative phase imaging (QPI) was implemented to image cells before and during subjugation of shear flow. Simultaneous evaluation of disorder strength and cellular stiffness showed a correlation between the two metrics.

Authors
Eldridge, WJ; Loomis, B; Wax, A; Eldridge, WJ; Loomis, B; Wax, A
MLA Citation
Eldridge, WJ, Loomis, B, Wax, A, Eldridge, WJ, Loomis, B, and Wax, A. "Linking cellular disorder strength and shear stiffness using quantitative phase imagingLinking cellular disorder strength and shear stiffness using quantitative phase imaging (PublishedPublished)." July 21, 2014.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2014
DOI
10.1364/FIO.2016.FF3A.6

Guidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissueGuidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissue

© OSA 2016. Here we present the analysis of two dimensional angle-resolved low coherence interferometry (2D a/LCI) measurements co-registered with optical coherence tomography (OCT) imaging to guide the a/LCI measurements on an esophageal cancer rat model.

Authors
Kim, S; Crose, M; Kresty, LA; Wax, A; Kim, S; Crose, M; Kresty, LA; Wax, A
MLA Citation
Kim, S, Crose, M, Kresty, LA, Wax, A, Kim, S, Crose, M, Kresty, LA, and Wax, A. "Guidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissueGuidance of angle-resolved low coherence interferometry using co-located optical coherence tomography on rat esophageal tissue (PublishedPublished)." July 21, 2014.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2014
DOI
10.1364/CANCER.2016.JTu3A.16

Clinical detection of cervical dysplasia using angle-resolved low coherence interferometryClinical detection of cervical dysplasia using angle-resolved low coherence interferometry

© OSA 2016. We assess the diagnostic capability of a/LCI in vivo for cervical cancer detection. The nuclear diameter was determined from the a/LCI scans using a Mie theory and a wavelet based hybrid analysis, and the results were compared to histopathology.

Authors
Ho, D; Drake, T; Smith-McCune, KK; Darragh, TM; Hwang, LY; Wax, A; Ho, D; Drake, T; Smith-McCune, KK; Darragh, TM; Hwang, LY; Wax, A
MLA Citation
Ho, D, Drake, T, Smith-McCune, KK, Darragh, TM, Hwang, LY, Wax, A, Ho, D, Drake, T, Smith-McCune, KK, Darragh, TM, Hwang, LY, and Wax, A. "Clinical detection of cervical dysplasia using angle-resolved low coherence interferometryClinical detection of cervical dysplasia using angle-resolved low coherence interferometry (PublishedPublished)." July 21, 2014.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2014
DOI
10.1364/CANCER.2016.CTh4A.2

Quantitative phase microscopy with off-axis optical coherence tomography.

We have developed a modality for quantitative phase imaging within spectral domain optical coherence tomography based on using an off-axis reference beam. By tilting the propagation of the reference beam relative to that of the sample beam, a spatially varying fringe is generated. Upon detection of this fringe using a parallel spectral domain scheme, the fringe can be used to separate the interference component of the signal and obtain the complex sample field. In addition to providing quantitative phase measurements within a depth resolved measurement, this approach also allows elimination of the complex conjugate artifact, a known limitation of spectral interferometry. The principle of the approach is described here along with demonstration of its capabilities using technical samples.

Authors
Rinehart, MT; Jaedicke, V; Wax, A
MLA Citation
Rinehart, MT, Jaedicke, V, and Wax, A. "Quantitative phase microscopy with off-axis optical coherence tomography." Optics letters 39.7 (April 2014): 1996-1999.
PMID
24686658
Source
epmc
Published In
Optics Letters
Volume
39
Issue
7
Publish Date
2014
Start Page
1996
End Page
1999
DOI
10.1364/ol.39.001996

Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

Authors
Rinehart, M; Grab, S; Rohan, L; Katz, D; Wax, A
MLA Citation
Rinehart, M, Grab, S, Rohan, L, Katz, D, and Wax, A. "Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry." PloS one 9.4 (January 2014): e95005-.
PMID
24736376
Source
epmc
Published In
PloS one
Volume
9
Issue
4
Publish Date
2014
Start Page
e95005
DOI
10.1371/journal.pone.0095005

Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms.

Traditional slit-based spectrometers have an inherent trade-off between spectral resolution and throughput that can limit their performance when measuring diffuse sources such as light returned from highly scattering biological tissue. Recently, multielement fiber bundles have been used to effectively measure diffuse sources, e.g., in the field of spatially offset Raman spectroscopy, by remapping the source (or some region of the source) into a slit shape for delivery to the spectrometer. Another approach is to change the nature of the instrument by using a coded entrance aperture, which can increase throughput without sacrificing spectral resolution.In this study, two spectrometers, one with a slit-based entrance aperture and the other with a coded aperture, were used to measure Raman spectra of an analyte as a function of the optical properties of an overlying scattering medium. Power-law fits reveal that the analyte signal is approximately proportional to the number of transport mean free paths of the scattering medium raised to a power of -0.47 (coded aperture instrument) or -1.09 (slit-based instrument). These results demonstrate that the attenuation in signal intensity is more pronounced for the slit-based instrument and highlight the scattering regimes where coded aperture instruments can provide an advantage over traditional slit-based spectrometers.

Authors
Maher, JR; Matthews, TE; Reid, AK; Katz, DF; Wax, A
MLA Citation
Maher, JR, Matthews, TE, Reid, AK, Katz, DF, and Wax, A. "Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms." Journal of Biomedical Optics 19.11 (January 2014): 117001-.
PMID
25371979
Source
epmc
Published In
Journal of Biomedical Optics
Volume
19
Issue
11
Publish Date
2014
Start Page
117001
DOI
10.1117/1.jbo.19.11.117001

Wavelet transform fast inverse light scattering analysis for size determination of spherical scatterers

© 2014 Optical Society of America.We present a fast approach for size determination of spherical scatterers using the continuous wavelet transform of the angular light scattering profile to address the computational limitations of previously developed sizing techniques. The potential accuracy, speed, and robustness of the algorithm were determined in simulated models of scattering by polystyrene beads and cells. The algorithm was tested experimentally on angular light scattering data from polystyrene bead phantoms and MCF-7 breast cancer cells using a 2D a/LCI system. Theoretical sizing of simulated profiles of beads and cells produced strong fits between calculated and actual size (r<sup>2</sup> = 0.9969 and r<sup>2</sup> = 0.9979 respectively), and experimental size determinations were accurate to within one micron.

Authors
Ho, D; Kim, S; Drake, TK; Eldridge, WJ; Wax, A
MLA Citation
Ho, D, Kim, S, Drake, TK, Eldridge, WJ, and Wax, A. "Wavelet transform fast inverse light scattering analysis for size determination of spherical scatterers." Biomedical Optics Express 5.10 (2014): 3292-3304.
Source
scival
Published In
Biomedical Optics Express
Volume
5
Issue
10
Publish Date
2014
Start Page
3292
End Page
3304
DOI
10.1364/BOE.5.003292

Fourier domain multispectral multiple scattering low coherence interferometry.

We have implemented multispectral multiple scattering low coherence interferometry (ms2/LCI) with Fourier domain data collection. The ms2/LCI system is designed to localize features with spectroscopic contrast with millimeter resolution up to 1 cm deep in scattering samples by using photons that have undergone multiple low-angle (forward) scattering events. Fourier domain detection both increases the data acquisition speed of the system and gives access to rich spectroscopic information, compared to the previous single channel, time-domain implementation. Separate delivery and detection angular apertures reduce collection of the diffuse background signal in order to isolate localized spectral features from deeper in scattering samples than would be possible with traditional spectroscopic optical coherence tomography. Light from a supercontinuum source is used to acquire absorption spectra of chromophores in the visible range within a tissue-like scattering phantom. An intensity modulation and digital lock-in detection scheme is implemented to mitigate relative intensity and spectral noise inherent in supercontinuum sources. The technical parameters of the system and comparative analysis are presented.

Authors
Matthews, TE; Giacomelli, MG; Brown, WJ; Wax, A
MLA Citation
Matthews, TE, Giacomelli, MG, Brown, WJ, and Wax, A. "Fourier domain multispectral multiple scattering low coherence interferometry." Applied optics 52.34 (December 2013): 8220-8228.
PMID
24513821
Source
epmc
Published In
Applied Optics
Volume
52
Issue
34
Publish Date
2013
Start Page
8220
End Page
8228
DOI
10.1364/ao.52.008220

Multimodal multiplex raman spectroscopy and optical coherence tomography of tissue for drug monitoring

We demonstrate efficient and high resolution Raman spectroscopy in tissue through a fiber bundle and the use of a custom multimodal multiplex spectrometer. Combined Raman and OCT measurements allow for drug monitoring in tissue explants. ©2013 The Optical Society (OSA).

Authors
Matthews, TE; Chuchuen, O; Katz, DF; Wax, A
MLA Citation
Matthews, TE, Chuchuen, O, Katz, DF, and Wax, A. "Multimodal multiplex raman spectroscopy and optical coherence tomography of tissue for drug monitoring." Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013 (November 19, 2013).
Source
scopus
Published In
Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013
Publish Date
2013

Wigner distribution: Friend to biophotonics

The Wigner distribution provides joint information of a signal in two conjugate domains. Unique insights can be obtained into biophotonics problems by using this formalism to examine the coherence of optical fields. © 2013 Optical Society of America.

Authors
Wax, A
MLA Citation
Wax, A. "Wigner distribution: Friend to biophotonics." Optics InfoBase Conference Papers (January 1, 2013).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2013

Measuring dilution of microbicide gels with optical imaging.

We present a novel approach for measuring topical microbicide gel dilution using optical imaging. The approach compares gel thickness measurements from fluorimetry and multiplexed low coherence interferometry in order to calculate dilution of a gel. As a microbicide gel becomes diluted at fixed thickness, its mLCI thickness measurement remains constant, while the fluorimetry signal decreases in intensity. The difference between the two measurements is related to the extent of gel dilution. These two optical modalities are implemented in a single endoscopic instrument that enables simultaneous data collection. A preliminary validation study was performed with in vitro placebo gel measurements taken in a controlled test socket. It was found that change in slope of the regression line between fluorimetry and mLCI based measurements indicates dilution. A dilution calibration curve was then generated by repeating the test socket measurements with serial dilutions of placebo gel with vaginal fluid simulant. This methodology can provide valuable dilution information on candidate microbicide products, which could substantially enhance our understanding of their in vivo functioning.

Authors
Drake, TK; Shah, T; Peters, JJ; Wax, A; Katz, DF
MLA Citation
Drake, TK, Shah, T, Peters, JJ, Wax, A, and Katz, DF. "Measuring dilution of microbicide gels with optical imaging." PloS one 8.12 (January 2013): e82213-.
PMID
24340006
Source
epmc
Published In
PloS one
Volume
8
Issue
12
Publish Date
2013
Start Page
e82213
DOI
10.1371/journal.pone.0082213

Nuclear morphology measurements with angle-resolved low coherence interferometry for application to cell biology and early cancer detection.

The study of intact, living cells using non-invasive optical spectroscopic methods offers the opportunity to assess cellular structure and organization in a way that is not possible with commonly used cell biology imaging techniques. We have developed a novel spectroscopic technique for diagnosing disease at the cellular level based on using low-coherence interferometry (LCI) to detect the angular distribution of scattered light. Angle-resolved LCI (a/LCI) combines the ability of LCI to isolate scattering from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales. In application to examining cellular structure, a/LCI enables quantitative measurements of changes in the size and texture of cell nuclei. These quantitative measurements are characteristic of different pathological states. The capabilities of a/LCI were demonstrated using a clinical system that can be applied in endoscopic surveillance of esophageal tissue, producing high sensitivity and specificity for detecting dysplastic tissues in vivo. Experiments with in vitro cell samples also show the utility of a/LCI in observing structural changes due to environmental stimuli as well as detecting apoptosis due to chemotherapeutic agents.

Authors
Wax, A; Chalut, KJ
MLA Citation
Wax, A, and Chalut, KJ. "Nuclear morphology measurements with angle-resolved low coherence interferometry for application to cell biology and early cancer detection." Studies in health technology and informatics 185 (January 2013): 129-151.
PMID
23542934
Source
epmc
Published In
Studies in health technology and informatics
Volume
185
Publish Date
2013
Start Page
129
End Page
151

Feasibility study of brain tumor delineation using immunolabeled gold nanorods

Effective treatment of patients with malignant brain tumors requires surgical resection of a high percentage of the bulk tumor. Surgeons require a method that enables delineation of tumor margins, which are not visually distinct by eye. In this study, the feasibility of using gold nanorods (GNRs) for this purpose is evaluated. Anti-Epidermal Growth Factor Receptor (anti-EGFR) conjugated GNRs are used to label human xenograft glioblastoma multiforme (GBM) tumors embedded within slices of brain tissues from healthy nude mice. The anti-EGFR GNRs exhibit enhanced absorption at red to near-infrared wavelengths, often referred to as the tissue optical window, where absorption from blood is minimal. To enable definition of molecular specificity and spatial accuracy of the label, the GNR absorption is compared with GFP fluorescence which is expressed by the GBM cells used here. This work demonstrates a simple but highly translational technique to classify normal and malignant brain tissue regions in open surgery applications using immunolabeled GNR contrast agents. © 2013 Optical Society of America.

Authors
Seekell, K; Lewis, S; Wilson, C; Li, S; Grant, G; Wax, A
MLA Citation
Seekell, K, Lewis, S, Wilson, C, Li, S, Grant, G, and Wax, A. "Feasibility study of brain tumor delineation using immunolabeled gold nanorods." Biomedical Optics Express 4.11 (2013): 2284-2295.
PMID
24298394
Source
scival
Published In
Biomedical Optics Express
Volume
4
Issue
11
Publish Date
2013
Start Page
2284
End Page
2295
DOI
10.1364/BOE.4.002284

A calibration standard for two-dimensional angle-resolved low-coherence interferometry

We have developed phantoms for use with two-dimensional angle-resolved lowcoherence interferometry. Here we demonstrate standardized multi-scale structural information for light scattering measurements. © 2013 The Optical Society.

Authors
Yarmoska, SK; Kim, S; Giacomelli, MG; Wax, A
MLA Citation
Yarmoska, SK, Kim, S, Giacomelli, MG, and Wax, A. "A calibration standard for two-dimensional angle-resolved low-coherence interferometry." Optical Trapping Applications, OTA 2013 (2013): JT2A.10-.
Source
scival
Published In
Optical Trapping Applications, OTA 2013
Publish Date
2013
Start Page
JT2A.10

Feasibility of brain tumor delineation using immunolabeled gold nanorods

The enhanced scattering of gold nanorods in the near-infrared regime provides excellent contrast for imaging within biological tissues. This study demonstrates the capability of anti-EGFR nanorods to distinguish xenograft glioblastomas from healthy murine brain tissue. ©2013 The Optical Society (OSA).

Authors
Seekell, K; Lewis, S; Wilson, C; Grant, G; Wax, A
MLA Citation
Seekell, K, Lewis, S, Wilson, C, Grant, G, and Wax, A. "Feasibility of brain tumor delineation using immunolabeled gold nanorods." Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013 (2013): MW1C.3-.
Source
scival
Published In
Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013
Publish Date
2013
Start Page
MW1C.3

Plasmonic nanoparticles as molecular contrast agents in interferometric imaging

Plasmonic nanoparticles offer unique optical characteristics, including strong spectrally distinct signatures which make them useful as contrast agents. Here various applications are presented and the benefits of nanoparticles are discussed. ©2013 The Optical Society (OSA).

Authors
Wax, A
MLA Citation
Wax, A. "Plasmonic nanoparticles as molecular contrast agents in interferometric imaging." Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013 (2013): MW1C.2-.
Source
scival
Published In
Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013
Publish Date
2013
Start Page
MW1C.2

A calibration standard for two-dimensional angle-resolved low-coherence interferometry

We have developed phantoms for use with two-dimensional angle-resolved lowcoherence interferometry. Here we demonstrate standardized multi-scale structural information for light scattering measurements. ©2013 The Optical Society (OSA).

Authors
Yarmoska, SK; Kim, S; Giacomelli, MG; Wax, A
MLA Citation
Yarmoska, SK, Kim, S, Giacomelli, MG, and Wax, A. "A calibration standard for two-dimensional angle-resolved low-coherence interferometry." Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013 (2013): JT2A.10-.
Source
scival
Published In
Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013
Publish Date
2013
Start Page
JT2A.10

A calibration standard for two-dimensional angle-resolved low-coherence interferometry

We have developed phantoms for use with two-dimensional angle-resolved lowcoherence interferometry. Here we demonstrate standardized multi-scale structural information for light scattering measurements. Optics in the Life Sciences Congress Technical Digest © 2013 The Optical Society (OSA).

Authors
Yarmoska, SK; Kim, S; Giacomelli, MG; Wax, A
MLA Citation
Yarmoska, SK, Kim, S, Giacomelli, MG, and Wax, A. "A calibration standard for two-dimensional angle-resolved low-coherence interferometry." Bio-Optics: Design and Application, BODA 2013 (2013): JT2A.10-.
Source
scival
Published In
Bio-Optics: Design and Application, BODA 2013
Publish Date
2013
Start Page
JT2A.10

A scattering phantom for observing long range order with two-dimensional angle-resolved low-coherence interferometry

Angle-resolved low coherence interferometry (a/LCI) is an approach for assessing tissue structure based on light scattering data. Recent advances in a/LCI have extended the analysis to study scattering distributions in two dimensions. In order to provide suitable scattering phantoms for 2D a/LCI, we have developed phantoms based on soft lithography which can provide a range of structures including long range order. Here we characterize these phantoms and demonstrate their utility for providing standardized multi-scale structural information for light scattering measurements. © 2013 Optical Society of America.

Authors
Yarmoska, SK; Kim, S; Matthews, TE; Wax, A
MLA Citation
Yarmoska, SK, Kim, S, Matthews, TE, and Wax, A. "A scattering phantom for observing long range order with two-dimensional angle-resolved low-coherence interferometry." Biomedical Optics Express 4.9 (2013): 1742-1748.
PMID
24049694
Source
scival
Published In
Biomedical Optics Express
Volume
4
Issue
9
Publish Date
2013
Start Page
1742
End Page
1748
DOI
10.1364/BOE.4.001742

Three-dimensional molecular imaging with photothermal optical coherence tomography

Optical coherence tomography (OCT) is a three-dimensional optical imaging technique that has been successfully implemented in ophthalmology for imaging the human retina, and in studying animal models of disease. OCT can nondestructively visualize structural features in tissue at cellular-level resolution, and can exploit contrast agents to achieve molecular contrast. Photothermal OCT relies on the heat-producing capabilities of antibody-conjugated gold nanoparticles to achieve molecular contrast. A pump laser at the nanoparticle resonance wavelength is used to heat the nanoparticles in the sample, and the resulting changes in the index of refraction around the nanoparticles are detected by phase-sensitive OCT. Lock-in detection of the pump beam amplitude-modulated frequency and the detector frequency allow for high-sensitivity images of molecular targets. This approach is attractive for nondestructive three-dimensional molecular imaging deep (approximately 2 mm) within biological samples. The protocols described here achieve a sensitivity of 14 parts per million (weight/weight) nanoparticles in the sample, which is sufficient to differentiate EGFR (epidermal growth factor receptor)- overexpressing cells from minimally expressing cells in three-dimensional cell constructs. © Springer Science+Business Media New York 2013.

Authors
Skala, MC; Crow, MJ; Wax, A; Izatt, JA
MLA Citation
Skala, MC, Crow, MJ, Wax, A, and Izatt, JA. "Three-dimensional molecular imaging with photothermal optical coherence tomography." Methods in Molecular Biology 1026 (2013): 85-92.
PMID
23749571
Source
scival
Published In
Methods in molecular biology (Clifton, N.J.)
Volume
1026
Publish Date
2013
Start Page
85
End Page
92
DOI
10.1007/978-1-62703-468-5-7

Polarization and Spectral Interferometric Techniques for Quantitative Phase Microscopy

Authors
Zhu, Y; Rinehart, MT; Robles, FE; Wax, A
MLA Citation
Zhu, Y, Rinehart, MT, Robles, FE, and Wax, A. "Polarization and Spectral Interferometric Techniques for Quantitative Phase Microscopy." Biomedical Optical Phase Microscopy and Nanoscopy (2013): 218-310.
Source
scival
Published In
Biomedical Optical Phase Microscopy and Nanoscopy
Publish Date
2013
Start Page
218
End Page
310
DOI
10.1016/B978-0-12-415871-9.00014-4

Comparative review of interferometric detection of plasmonic nanoparticles

Noble metal nanoparticles exhibit enhanced scattering and absorption at specific wavelengths due to a localized surface plamson resonance. This unique property can be exploited to enable the use of plasmonic nanoparticles as contrast agents in optical imaging. A range of optical techniques have been developed to detect nanoparticles in order to implement imaging schemes. Here we review several different approaches for using optical interferometry to detect the presence and concentration of nanoparticles. The strengths and weaknesses of the various approaches are discussed and quantitative comparisons of the achievable signal to noise ratios are presented. The benefits of each approach are outlined as they relate to specific application goals. © 2013 Optical Society of America.

Authors
Wax, A; Meiri, A; Arumugam, S; Rinehart, MT
MLA Citation
Wax, A, Meiri, A, Arumugam, S, and Rinehart, MT. "Comparative review of interferometric detection of plasmonic nanoparticles." Biomedical Optics Express 4.10 (2013): 2166-2178.
PMID
24156072
Source
scival
Published In
Biomedical Optics Express
Volume
4
Issue
10
Publish Date
2013
Start Page
2166
End Page
2178
DOI
10.1364/BOE.4.002166

Coherence imaging for early cancer detection

We have developed multiple spectroscopic coherence imaging methods to assess pre-cancerous states by isolating scattering signatures from specific tissue locations. We describe the basis, validation and development of the approaches and recent clinical results. © 2012 OSA.

Authors
Wax, A
MLA Citation
Wax, A. "Coherence imaging for early cancer detection." 2012 Conference on Lasers and Electro-Optics, CLEO 2012 (December 6, 2012).
Source
scopus
Published In
2012 Conference on Lasers and Electro-Optics, CLEO 2012
Publish Date
2012

Spectrally multiplexed photothermal OCT and novel detection methods

We demonstrate simultaneous detection of two nanoparticle species using phase-sensitive optical coherence tomography with photothermal excitation at two wavelengths matched to the distinct absorption peaks of the nanoparticles. To minimize bulk heating of the sample, a novel single-pulse excitation scheme is proposed and its sensitivity is characterized. © 2012 OSA.

Authors
Kim, S; Rinehart, MT; Zhu, Y; Wax, A
MLA Citation
Kim, S, Rinehart, MT, Zhu, Y, and Wax, A. "Spectrally multiplexed photothermal OCT and novel detection methods." 2012 Conference on Lasers and Electro-Optics, CLEO 2012 (December 6, 2012).
Source
scopus
Published In
2012 Conference on Lasers and Electro-Optics, CLEO 2012
Publish Date
2012

Assessing nanoparticle concentration using METRiCS optical coherence tomography

We have recently developed METRiCS OCT to provide spatially resolved molecular information of chromosomes. Here we apply this method to measure the extinction spectra of nanoparticles at various concentrations for potential in vivo applications. © 2010 Optical Society of America.

Authors
Li, Y; Robles, FE; Seekell, K; Wax, AP
MLA Citation
Li, Y, Robles, FE, Seekell, K, and Wax, AP. "Assessing nanoparticle concentration using METRiCS optical coherence tomography." Biomedical Optics, BIOMED 2012 (December 1, 2012).
Source
scopus
Published In
Biomedical Optics, BIOMED 2012
Publish Date
2012

Spectral-domain differential interference contrast (SD-DIC) microscopy for measuring live cell dynamics

We present live cell imaging using spectral-domain differential interference contrast microscopy, a novel technique for high-resolution, quantitative measurement of optical pathlength gradients. Imaging and dynamic monitoring of live neurons and cardiomyocytes were demonstrated. © 2012 OSA.

Authors
Zhu, Y; Lyons, MR; West, AE; Satterwhite, LL; Wax, A
MLA Citation
Zhu, Y, Lyons, MR, West, AE, Satterwhite, LL, and Wax, A. "Spectral-domain differential interference contrast (SD-DIC) microscopy for measuring live cell dynamics." Biomedical Optics, BIOMED 2012 (December 1, 2012).
Source
scopus
Published In
Biomedical Optics, BIOMED 2012
Publish Date
2012

Spectrally multiplexed photothermal OCT and novel detection methods

We demonstrate simultaneous detection of two nanoparticle species using phasesensitive optical coherence tomography with photothermal excitation at two wavelengths matched to the distinct absorption peaks of the nanoparticles. To minimize bulk heating of the sample, a novel single-pulse excitation scheme is proposed and its sensitivity is characterized. © OSA 2012.

Authors
Kim, S; Rinehart, MT; Zhu, Y; Wax, A
MLA Citation
Kim, S, Rinehart, MT, Zhu, Y, and Wax, A. "Spectrally multiplexed photothermal OCT and novel detection methods." CLEO: Science and Innovations, CLEO_SI 2012 (December 1, 2012).
Source
scopus
Published In
CLEO: Science and Innovations, CLEO_SI 2012
Publish Date
2012

Spectrally multiplexed photothermal OCT and novel detection methods

We demonstrate simultaneous detection of two nanoparticle species using phasesensitive optical coherence tomography with photothermal excitation at two wavelengths matched to the distinct absorption peaks of the nanoparticles. To minimize bulk heating of the sample, a novel single-pulse excitation scheme is proposed and its sensitivity is characterized. © OSA 2012.

Authors
Kim, S; Rinehart, MT; Zhu, Y; Wax, A
MLA Citation
Kim, S, Rinehart, MT, Zhu, Y, and Wax, A. "Spectrally multiplexed photothermal OCT and novel detection methods." CLEO: Applications and Technology, CLEO_AT 2012 (December 1, 2012).
Source
scopus
Published In
CLEO: Applications and Technology, CLEO_AT 2012
Publish Date
2012

Novel optical signature for sickle cell trait red blood cells

We identified unique optical signatures for sickle cell trait, a condition where heterozygous individuals are carriers for the hemoglobin allele that causes sickle cell anemia, by using wide-field interferometric microscopy. © OSA 2012.

Authors
Satterwhite, LL; Shaked, NT; Cyr, DD; Telen, MJ; Truskey, GA; Wax, A
MLA Citation
Satterwhite, LL, Shaked, NT, Cyr, DD, Telen, MJ, Truskey, GA, and Wax, A. "Novel optical signature for sickle cell trait red blood cells." Frontiers in Optics, FIO 2012 (December 1, 2012).
Source
scopus
Published In
Frontiers in Optics, FIO 2012
Publish Date
2012

In vivo optical imaging of human vaginal gel thickness distributions with a probe-based, dual-modality instrument.

ABSTRACT. We used a probe-based dual-modality optical imaging instrument to measure in vivo coating thickness distributions of a gel distributed along the vaginal lumen, in a clinical study. The gel was a surrogate for one delivering an anti-HIV topical microbicide. Imaging data from Fourier-domain multiplexed low-coherence interferometry (mLCI) and fluorimetric measurements were compared to assess the feasibility and accuracy of mLCI in measuring in vivo gel coating thickness distributions. In each study session, 3.5 mL of Replens gel was inserted to the vaginal fornix while the participant was supine. The participant either: 1. remained supine (10 or 60 min); or 2. sat up (1 min), stood up (1 min), sat down (1 min) and returned to the supine position; net elapsed time was 10 or 60 min after which the gel distribution was imaged. Local coating thickness distributions were qualitatively and quantitatively similar. Here mLCI did not accurately measure thicker gel coatings (>0.8  mm), a limitation not seen with fluorimetry. However, mLCI is capable of measuring in vivo microbicide gel distributions with resolution on the order of 10 μm, without the need for exogenous contrast agents, and can accurately capture relevant summary coating measures in good agreement with fluorimetry.

Authors
Drake, TK; DeSoto, MG; Peters, JJ; Henderson, MH; Thiele, B; Bishop, TS; Murtha, AP; Katz, DF; Wax, A
MLA Citation
Drake, TK, DeSoto, MG, Peters, JJ, Henderson, MH, Thiele, B, Bishop, TS, Murtha, AP, Katz, DF, and Wax, A. "In vivo optical imaging of human vaginal gel thickness distributions with a probe-based, dual-modality instrument." J Biomed Opt 17.11 (November 2012): 116014-.
PMID
23117809
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
17
Issue
11
Publish Date
2012
Start Page
116014
DOI
10.1117/1.JBO.17.11.116014

Dynamic quantitative microscopy and nanoscopy of red blood cells in sickle cell disease

We have applied wide-field digital interferometric techniques to quantitatively image sickle red blood cells (RBCs) [1] in a noncontact label-free manner, and measure the nanometer-scale fluctuations in their thickness as an indication of their stiffness. The technique can simultaneously measure the fluctuations for multiple spatial points on the RBC and thus yields a map describing the stiffness of each RBC in the field of view. Using this map, the local rigidity regions of the RBC are evaluated quantitatively. Since wide-field digital interferometry is a quantitative holographic imaging technique rather than one-point measurement, it can be used to simultaneously evaluate cell transverse morphology plus thickness in addition to its stiffness profile. Using this technique, we examine the morphology and dynamics of RBCs from individuals who suffer from sickle cell disease, and find that the sickle RBCs are significantly stiffer than healthy RBCs. Furthermore, we show that the technique is sensitive enough to distinguish various classes of sickle RBCs, including sickle RBCs with visibly-normal morphology, compared to the stiffer crescent-shaped sickle RBCs. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Authors
Shaked, NT; Satterwhite, LL; Telen, MJ; Truskey, GA; Wax, A
MLA Citation
Shaked, NT, Satterwhite, LL, Telen, MJ, Truskey, GA, and Wax, A. "Dynamic quantitative microscopy and nanoscopy of red blood cells in sickle cell disease." 2012.
Source
scival
Published In
Proceedings of SPIE
Volume
8227
Publish Date
2012
DOI
10.1117/12.907659

Multispectral nanoparticle contrast agents for true-color spectroscopic optical coherence tomography

We have recently developed a novel dual window scheme for processing spectroscopic OCT images to provide spatially resolved true color imaging of chromophores in scattering samples. Here we apply this method to measure the extinction spectra of plasmonic nanoparticles at various concentrations for potential in vivo applications. We experimentally demonstrate sub-nanomolar sensitivity in the measurement of nanoparticle concentrations, and show that colorimetric imaging with multiple species of nanoparticles produces enhanced contrast for spectroscopic OCT in both tissue phantom and cell studies. © 2012 Optical Society of America.

Authors
Li, YL; Seekell, K; Yuan, H; Robles, FE; Wax, A
MLA Citation
Li, YL, Seekell, K, Yuan, H, Robles, FE, and Wax, A. "Multispectral nanoparticle contrast agents for true-color spectroscopic optical coherence tomography." Biomedical Optics Express 3.8 (2012): 1914-1923.
PMID
22876354
Source
scival
Published In
Biomedical Optics Express
Volume
3
Issue
8
Publish Date
2012
Start Page
1914
End Page
1923
DOI
10.1364/BOE.3.001914

Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis

Noble metal nanoparticles hold great potential as optical contrast agents due to a unique feature, known as the plasmon resonance, which produces enhanced scattering and absorption at specific frequencies. The plasmon resonance also provides a spectral tunability that is not often found in organic fluorophores or other labeling methods. The ability to functionalize these nanoparticles with antibodies has led to their development as contrast agents for molecular optical imaging. In this review article, we present methods for optimizing the spectral agility of these labels. We discuss synthesis of gold nanorods, a plasmonic nanoparticle in which the plasmonic resonance can be tuned during synthesis to provide imaging within the spectral window commonly utilized in biomedical applications. We describe recent advances in our group to functionalize gold and silver nanoparticles using distinct antibodies, including EGFR, HER-2 and IGF-1, selected for their relevance to tumor imaging. Finally, we present characterization of these nanoparticle labels to verify their spectral properties and molecular specificity. © 2011 Elsevier Inc.

Authors
Seekell, K; Price, H; Marinakos, S; Wax, A
MLA Citation
Seekell, K, Price, H, Marinakos, S, and Wax, A. "Optimization of immunolabeled plasmonic nanoparticles for cell surface receptor analysis." Methods 56.2 (2012): 310-316.
PMID
21911063
Source
scival
Published In
Methods
Volume
56
Issue
2
Publish Date
2012
Start Page
310
End Page
316
DOI
10.1016/j.ymeth.2011.08.017

Quantitative phase spectroscopy

Quantitative phase spectroscopy is presented as a novel method of measuring the wavelength-dependent refractive index of microscopic volumes. Light from a broadband source is filtered to an ~5 nm bandwidth and rapidly tuned across the visible spectrum in 1 nm increments by an acousto-optic tunable filter (AOTF). Quantitative phase images of semitransparent samples are recovered at each wavelength using off-axis interferometry and are processed to recover relative and absolute dispersion measurements. We demonstrate the utility of this approach by (i) spectrally averaging phase images to reduce coherent noise, (ii) measuring absorptive and dispersive features in microspheres, and (iii) quantifying bulk hemoglobin concentrations by absolute refractive index measurements. Considerations of using low coherence illumination and the extension of spectral techniques in quantitative phase measurements are discussed. © 2012 Optical Society of America.

Authors
Rinehart, M; Zhu, Y; Wax, A
MLA Citation
Rinehart, M, Zhu, Y, and Wax, A. "Quantitative phase spectroscopy." Biomedical Optics Express 3.5 (2012): 958-965.
PMID
22567588
Source
scival
Published In
Biomedical Optics Express
Volume
3
Issue
5
Publish Date
2012
Start Page
958
End Page
965
DOI
10.1364/BOE.3.000958

Spectrally multiplexed photothermal OCT and novel detection methods

We demonstrate simultaneous detection of two nanoparticle species using phase-sensitive optical coherence tomography with photothermal excitation at two wavelengths matched to the distinct absorption peaks of the nanoparticles. To minimize bulk heating of the sample, a novel single-pulse excitation scheme is proposed and its sensitivity is characterized. © 2012 OSA.

Authors
Kim, S; Rinehart, MT; Zhu, Y; Wax, A
MLA Citation
Kim, S, Rinehart, MT, Zhu, Y, and Wax, A. "Spectrally multiplexed photothermal OCT and novel detection methods." 2012 Conference on Lasers and Electro-Optics, CLEO 2012 (2012).
Source
scival
Published In
2012 Conference on Lasers and Electro-Optics, CLEO 2012
Publish Date
2012

Coherence imaging for early cancer detection

We have developed multiple spectroscopic coherence imaging methods to assess pre-cancerous states by isolating scattering signatures from specific tissue locations. We describe the basis, validation and development of the approaches and recent clinical results. © 2012 OSA.

Authors
Wax, A
MLA Citation
Wax, A. "Coherence imaging for early cancer detection." 2012 Conference on Lasers and Electro-Optics, CLEO 2012 (2012).
Source
scival
Published In
2012 Conference on Lasers and Electro-Optics, CLEO 2012
Publish Date
2012

High-efficiency diffuse raman spectroscopy through a fiber bundle

Conventional spectrometers are limited in the amount of light they accept because of the requirement for narrow input apertures. A trade-off must generally be made between spectral resolution and input aperture width. This is especially a problem for performing spectroscopy on diffuse sources, such as with tissue, from which signal light has a broad spatial distribution. We introduce a method for achieving good spectral resolution from a fiber bundle input. The image of a fiber bundle has a characteristic structure. By distorting this image optically, we generate a pseudo-orthogonal intensity mask at the input of the spectrometer. The pseudo-orthogonal properties of the mask then allow decoupling at the detector plane of wavelength from spatial position. As long as the distorted image of the fiber bundle is well known, a spectrum can be recovered with spectral resolution equivalent to that of a conventional slit-based spectrometer. We demonstrate successful recovery of narrowly spaced spectral features as well as Raman spectra from a highly scattering sample with this method. This method enables probes with much higher throughputs and add fiber bundle-based spectroscopy to endoscopic designs. © 2012 IEEE.

Authors
Matthews, TE; Wax, A
MLA Citation
Matthews, TE, and Wax, A. "High-efficiency diffuse raman spectroscopy through a fiber bundle." Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS (2012): 1181-1183.
PMID
23366108
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Publish Date
2012
Start Page
1181
End Page
1183
DOI
10.1109/EMBC.2012.6346147

Phase-sensitive OCT imaging of multiple nanoparticle species using spectrally multiplexed single pulse photothermal excitation

We apply phase-sensitive optical coherence tomography to image multiple nanoparticle species with two excitation wavelengths matched to their distinct absorption peaks. Using different modulation frequencies, multiple species collocated within the sample can be distinguished. In addition, we characterize single-pulse excitation schemes as a method to minimize bulk heating of the sample. We demonstrate this new scheme with B-mode photothermal measurements of tissue phantoms. © 2012 Optical Society of America.

Authors
Kim, S; Rinehart, MT; Park, H; Zhu, Y; Wax, A
MLA Citation
Kim, S, Rinehart, MT, Park, H, Zhu, Y, and Wax, A. "Phase-sensitive OCT imaging of multiple nanoparticle species using spectrally multiplexed single pulse photothermal excitation." Biomedical Optics Express 3.10 (2012): 2579-2586.
PMID
23082297
Source
scival
Published In
Biomedical Optics Express
Volume
3
Issue
10
Publish Date
2012
Start Page
2579
End Page
2586
DOI
10.1364/BOE.3.002579

Imaging contrast and resolution in multiply scattered low coherence interferometry

With recent results demonstrating imaging using low coherence interferometry to detect multiply scattered light, signal attenuation and imaging resolution remains to be an open question. To address this, we present detailed modeling results of light propagation in the multiply scattered low-coherence interferometry (ms/LCI) configuration. Analytical and Monte Carlo models are used to assess the theoretical resolution and contrast of the system, and to explore the effect of media anisotropy on imaging parameters. Imaging resolution and depth penetration are found to depend on the fraction of photons scattered into a narrow range of forward scattering angles rather than the overall media anisotropy. © 2011 IEEE.

Authors
Giacomelli, MG; Wax, A
MLA Citation
Giacomelli, MG, and Wax, A. "Imaging contrast and resolution in multiply scattered low coherence interferometry." IEEE Journal on Selected Topics in Quantum Electronics 18.3 (2012): 1050-1058.
Source
scival
Published In
IEEE Journal of Selected Topics in Quantum Electronics
Volume
18
Issue
3
Publish Date
2012
Start Page
1050
End Page
1058
DOI
10.1109/JSTQE.2011.2161272

Angle-resolved low-coherence interferometry: An optical biopsy technique for clinical detection of dysplasia in Barretts esophagus

Angle-resolved low-coherence interferometry (a/LCI) is an optical biopsy technique that measures scattered light from tissue to determine nuclear size with submicron-level accuracy. The a/LCI probe can be deployed through the accessory channel of a standard endoscope and provides feedback to physicians to guide physical biopsies. The technique has been validated in animal and ex vivo human studies, and has been used to detect dysplasia in Barretts esophagus patients in vivo. In a recent clinical study of 46 Barretts esophagus patients, a/LCI was able to detect dysplasia with 100% sensitivity and 84% specificity. This report reviews the technique and discusses its potential clinical utility.

Authors
Zhu, Y; Terry, NG; Wax, A
MLA Citation
Zhu, Y, Terry, NG, and Wax, A. "Angle-resolved low-coherence interferometry: An optical biopsy technique for clinical detection of dysplasia in Barretts esophagus." Expert Review of Gastroenterology and Hepatology 6.1 (2012): 37-41.
PMID
22149580
Source
scival
Published In
Expert review of gastroenterology & hepatology
Volume
6
Issue
1
Publish Date
2012
Start Page
37
End Page
41
DOI
10.1586/egh.11.83

Optical spectroscopy of biological cells

Optical spectroscopy has seen expanding use for the study of biological cells in recent years. An overview of relevant spectroscopic techniques is presented, and applications to biological cells are reviewed. © 2010 Optical Society of America.

Authors
Wax, A; Giacomelli, MG; Matthews, TE; Rinehart, MT; Robles, FE; Zhu, Y
MLA Citation
Wax, A, Giacomelli, MG, Matthews, TE, Rinehart, MT, Robles, FE, and Zhu, Y. "Optical spectroscopy of biological cells." Advances in Optics and Photonics 4.3 (2012): 322-378.
Source
scival
Published In
Advances in Optics and Photonics
Volume
4
Issue
3
Publish Date
2012
Start Page
322
End Page
378
DOI
10.1364/AOP.4.000322

High-efficiency diffuse Raman spectroscopy through a fiber bundle.

Conventional spectrometers are limited in the amount of light they accept because of the requirement for narrow input apertures. A trade-off must generally be made between spectral resolution and input aperture width. This is especially a problem for performing spectroscopy on diffuse sources, such as with tissue, from which signal light has a broad spatial distribution. We introduce a method for achieving good spectral resolution from a fiber bundle input. The image of a fiber bundle has a characteristic structure. By distorting this image optically, we generate a pseudo-orthogonal intensity mask at the input of the spectrometer. The pseudo-orthogonal properties of the mask then allow decoupling at the detector plane of wavelength from spatial position. As long as the distorted image of the fiber bundle is well known, a spectrum can be recovered with spectral resolution equivalent to that of a conventional slit-based spectrometer. We demonstrate successful recovery of narrowly spaced spectral features as well as Raman spectra from a highly scattering sample with this method. This method enables probes with much higher throughputs and add fiber bundle-based spectroscopy to endoscopic designs.

Authors
Matthews, TE; Wax, A
MLA Citation
Matthews, TE, and Wax, A. "High-efficiency diffuse Raman spectroscopy through a fiber bundle." Conference proceedings : .. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 2012 (2012): 1181-1183.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
2012
Publish Date
2012
Start Page
1181
End Page
1183
DOI
10.1109/EMBC.2012.6346147

Controlled synthesis of gold nanorods and application to brain tumor delineation

Gold nanorods are candidates for tumor delineation due to their unique optical properties and biocompatibility. The optical characteristics of nanorods are tuned during synthesis. Anti-EGFR nanorods effectively label tumors within brain slices. © 2011 OSA.

Authors
Seekell, K; Wilson, C; Price, H; Grant, G; Wax, A
MLA Citation
Seekell, K, Wilson, C, Price, H, Grant, G, and Wax, A. "Controlled synthesis of gold nanorods and application to brain tumor delineation." Optics InfoBase Conference Papers (December 1, 2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy.

Quantitative phase microscopy is applied to image temporal changes in the refractive index (RI) distributions of solutions created by microbicidal films undergoing hydration. We present a novel method of using an engineered polydimethylsiloxane structure as a static phase reference to facilitate calibration of the absolute RI across the entire field. We present a study of dynamic structural changes in microbicidal films during hydration and subsequent dissolution. With assumptions about the smoothness of the phase changes induced by these films, we calculate absolute changes in the percentage of film in regions across the field of view.

Authors
Rinehart, MT; Drake, TK; Robles, FE; Rohan, LC; Katz, D; Wax, A
MLA Citation
Rinehart, MT, Drake, TK, Robles, FE, Rohan, LC, Katz, D, and Wax, A. "Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy." Journal of biomedical optics 16.12 (December 1, 2011): 120510-. (Letter)
Source
scopus
Published In
Journal of Biomedical Optics
Volume
16
Issue
12
Publish Date
2011
Start Page
120510

Preface

Authors
Ferraro, P; Wax, AP; Zalevsky, Z
MLA Citation
Ferraro, P, Wax, AP, and Zalevsky, Z. Preface. December 1, 2011.
Source
scopus
Volume
46
Publish Date
2011

Nonlinear phase dispersion spectroscopy.

Nonlinear phase dispersion spectroscopy is introduced as a means to retrieve wideband, high spectral resolution profiles of the wavelength-dependent real part of the refractive index. The method is based on detecting dispersion effects imparted to a light field with low coherence transmitted through a thin sample and detected interferometrically in the spectral domain. The same sampled signal is also processed to yield quantitative phase maps and spectral information regarding the total attenuation coefficient using spectral-domain phase microscopy and spectroscopic optical coherence tomography (SOCT), respectively. Proof-of-concept experiments using fluorescent and nonfluorescent polystyrene beads and another using a red blood cell demonstrate the ability of the method to quantify various absorptive/dispersive features. The increased sensitivity of this method, novel to our knowledge, is compared to intensity-based spectroscopy (e.g., SOCT), and potential applications are discussed.

Authors
Robles, FE; Satterwhite, LL; Wax, A
MLA Citation
Robles, FE, Satterwhite, LL, and Wax, A. "Nonlinear phase dispersion spectroscopy." Opt Lett 36.23 (December 1, 2011): 4665-4667.
PMID
22139277
Source
pubmed
Published In
Optics Letters
Volume
36
Issue
23
Publish Date
2011
Start Page
4665
End Page
4667

Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles.

This work presents simultaneous imaging and detection of three different cell receptors using three types of plasmonic nanoparticles (NPs). The size, shape, and composition-dependent scattering profiles of these NPs allow for a system of multiple distinct molecular markers using a single optical source. With this goal in mind, tags consisting of anti-epidermal growth factor receptor gold nanorods, anti-insulin-like growth factor 1-R silver nanospheres, and human epidermal growth factor receptor 2Ab gold nanospheres were developed to monitor the expression of receptors commonly overexpressed by cancer cells. These labels were chosen because they scatter strongly in distinct spectral windows. A hyperspectral darkfield microspectroscopy system was developed to record the scattering spectra of cells labeled with these molecular tags. Simultaneous monitoring of multiple tags may lead to applications such as profiling of cell line immunophenotype and investigation of receptor signaling pathways. Single, dual, and triple tag experiments were performed to analyze NP tag specificity as well as their interactions. Distinct resonance peaks were observed in these studies, showing the ability to characterize cell lines using conjugated NPs. However, interpreting shifts in these peaks due to changes in a cellular dielectric environment may be complicated by plasmon coupling between NPs bound to proximal receptors and other coupling mechanisms due to the receptors themselves.

Authors
Seekell, K; Crow, MJ; Marinakos, S; Ostrander, J; Chilkoti, A; Wax, A
MLA Citation
Seekell, K, Crow, MJ, Marinakos, S, Ostrander, J, Chilkoti, A, and Wax, A. "Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles." J Biomed Opt 16.11 (November 2011): 116003-.
PMID
22112108
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
16
Issue
11
Publish Date
2011
Start Page
116003
DOI
10.1117/1.3646529

Detection of intestinal dysplasia using angle-resolved low coherence interferometry.

Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique that allows for depth-resolved, label-free measurement of the average size and optical density of cell nuclei in epithelial tissue to assess the tissue health. a/LCI has previously been used clinically to identify the presence of dysplasia in Barrett's Esophagus patients undergoing routine surveillance. We present the results of a pilot, ex vivo study of tissues from 27 patients undergoing partial colonic resection surgery, conducted to evaluate the ability of a/LCI to identify dysplasia. Performance was determined by comparing the nuclear morphology measurements with pathological assessment of co-located physical biopsies. A statistically significant correlation between increased average nuclear size, reduced nuclear density, and the presence of dysplasia was noted at the basal layer of the epithelium, at a depth of 200 to 300 μm beneath the tissue surface. Using a decision line determined from a receiver operating characteristic, a/LCI was able to separate dysplastic from healthy tissues with a sensitivity of 92.9% (13/14), a specificity of 83.6% (56/67), and an overall accuracy of 85.2% (69/81). The study illustrates the extension of the a/LCI technique to the detection of intestinal dysplasia, and demonstrates the need for future in vivo studies.

Authors
Terry, N; Zhu, Y; Thacker, JKM; Migaly, J; Guy, C; Mantyh, CR; Wax, A
MLA Citation
Terry, N, Zhu, Y, Thacker, JKM, Migaly, J, Guy, C, Mantyh, CR, and Wax, A. "Detection of intestinal dysplasia using angle-resolved low coherence interferometry." Journal of Biomedical Optics 16.10 (October 2011): 106002-.
PMID
22029349
Source
epmc
Published In
Journal of Biomedical Optics
Volume
16
Issue
10
Publish Date
2011
Start Page
106002
DOI
10.1117/1.3631799

Stem cell differentiation indicated by noninvasive photonic characterization and fractal analysis of subcellular architecture.

We hypothesised that global structural changes in stem cells would manifest with differentiation, and that these changes would be observable with light scattering microscopy. Analysed with a fractal dimension formalism, we observed significant structural changes in differentiating human mesenchymal stem cells within one day after induction, earlier than could be detected by gene expression profiling. Moreover, light scattering microscopy is entirely non-perturbative, so the same sample could be monitored throughout the differentiation process. We explored one possible mechanism, chromatin remodelling, to account for the changes we observed. Correlating with the staining of HP1α, a heterochromatin protein, we applied novel microscopy methods and fractal analysis to monitor the plastic dynamics of chromatin within stem cell nuclei. We showed that the level of chromatin condensation changed during differentiation, and provide one possible explanation for the changes seen with the light scattering method. These results lend physical insight into stem cell differentiation while providing physics-based methods for non-invasive detection of the differentiation process.

Authors
Chalut, KJ; Kulangara, K; Wax, A; Leong, KW
MLA Citation
Chalut, KJ, Kulangara, K, Wax, A, and Leong, KW. "Stem cell differentiation indicated by noninvasive photonic characterization and fractal analysis of subcellular architecture." Integr Biol (Camb) 3.8 (August 2011): 863-867.
PMID
21695342
Source
pubmed
Published In
Integrative Biology
Volume
3
Issue
8
Publish Date
2011
Start Page
863
End Page
867
DOI
10.1039/c1ib00003a

Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry.

We have applied wide-field digital interferometry (WFDI) to examine the morphology and dynamics of live red blood cells (RBCs) from individuals who suffer from sickle cell anemia (SCA), a genetic disorder that affects the structure and mechanical properties of RBCs. WFDI is a noncontact, label-free optical microscopy approach that can yield quantitative thickness profiles of RBCs and measurements of their membrane fluctuations at the nanometer scale reflecting their stiffness. We find that RBCs from individuals with SCA are significantly stiffer than those from a healthy control. Moreover, we show that the technique is sensitive enough to distinguish classes of RBCs in SCA, including sickle RBCs with apparently normal morphology, compared to the stiffer crescent-shaped sickle RBCs. We expect that this approach will be useful for diagnosis of SCA and for determining efficacy of therapeutic agents.

Authors
Shaked, NT; Satterwhite, LL; Telen, MJ; Truskey, GA; Wax, A
MLA Citation
Shaked, NT, Satterwhite, LL, Telen, MJ, Truskey, GA, and Wax, A. "Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry." J Biomed Opt 16.3 (March 2011): 030506-. (Letter)
PMID
21456860
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
16
Issue
3
Publish Date
2011
Start Page
030506
DOI
10.1117/1.3556717

Spectral-domain differential interference contrast microscopy.

We present a fiber-optic low-coherence imaging technique, termed spectral-domain differential interference contrast microscopy (SD-DIC), for quantitative DIC imaging of both reflective surfaces and transparent biological specimens. SD-DIC combines the common-path nature of a Nomarski DIC interferometer with the high sensitivity of spectral-domain low-coherence interferometry to obtain high-resolution, quantitative measurements of optical pathlength gradients from a single point on the sample. Full-field imaging can be achieved by scanning the sample. A reflected-light SD-DIC system was demonstrated using a USAF resolution target as the phase object. Live cardiomyocytes were also imaged, achieving a resolution of 36 pm for pathlength gradient measurements. The dynamics of cardiomyocyte contraction were recorded with high sensitivity at selected sites on the cells.

Authors
Zhu, Y; Shaked, NT; Satterwhite, LL; Wax, A
MLA Citation
Zhu, Y, Shaked, NT, Satterwhite, LL, and Wax, A. "Spectral-domain differential interference contrast microscopy." Opt Lett 36.4 (February 15, 2011): 430-432.
PMID
21326412
Source
pubmed
Published In
Optics Letters
Volume
36
Issue
4
Publish Date
2011
Start Page
430
End Page
432

Multimodal optical detection of intravaginal microbicide gel coating thickness distribution

A clinical optical imaging probe incorporating simultaneous fluorescence and low coherence interferometry (LCI) imaging optics was developed. A clinical study was performed to compare LCI and fluorimetry in measuring intravaginal microbicide gel coating thickness distribution. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Drake, T; Peters, J; Henderson, M; DeSoto, M; Katz, D; Wax, A
MLA Citation
Drake, T, Peters, J, Henderson, M, DeSoto, M, Katz, D, and Wax, A. "Multimodal optical detection of intravaginal microbicide gel coating thickness distribution." Optics InfoBase Conference Papers (January 1, 2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Spectroscopic optical coherence tomography for quantitative molecular imaging

Advances in spectroscopic OCT have allowed for quantitative analysis of endogenous contrast agents. Here, we will use SOCT to achieve quantitative molecular imaging using various exogenous contrast agents spanning the visible region of the spectrum. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Robles, FE; Wax, A
MLA Citation
Robles, FE, and Wax, A. "Spectroscopic optical coherence tomography for quantitative molecular imaging." Optics InfoBase Conference Papers (January 1, 2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Quantitative analysis of three-dimensional biological cells using interferometric microscopy

Live biological cells are three-dimensional microscopic objects that constantly adjust their sizes, shapes and other biophysical features. Wide-field digital interferometry (WFDI) is a holographic technique that is able to record the complex wavefront of the light which has interacted with in-vitro cells in a single camera exposure, where no exogenous contrast agents are required. However, simple quasi-three-dimensional holographic visualization of the cell phase profiles need not be the end of the process. Quantitative analysis should permit extraction of numerical parameters which are useful for cytology or medical diagnosis. Using a transmission-mode setup, the phase profile represents the multiplication between the integral refractive index and the thickness of the sample. These coupled variables may not be distinct when acquiring the phase profiles of dynamic cells. Many morphological parameters which are useful for cell biologists are based on the cell thickness profile rather than on its phase profile. We first overview methods to decouple the cell thickness and its refractive index using the WFDI-based phase profile. Then, we present a whole-cell-imaging approach which is able to extract useful numerical parameters on the cells even in cases where decoupling of cell thickness and refractive index is not possible or desired. © 2011 SPIE.

Authors
Shaked, NT; Wax, A
MLA Citation
Shaked, NT, and Wax, A. "Quantitative analysis of three-dimensional biological cells using interferometric microscopy." Proceedings of SPIE - The International Society for Optical Engineering 8043 (January 1, 2011).
Source
scopus
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
8043
Publish Date
2011
DOI
10.1117/12.882357

Photothermal optical coherence tomography for molecular imaging

Molecular imaging using Photothermal Optical Coherence Tomography (OCT) was demonstrated with antibody-conjugated gold nanoparticles in phantoms and three-dimensional tissue constructs. Cells over-expressing the epidermal growth factor receptor (EGFR) were differentiated from under-expressing cells in three-dimensions. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Skala, MC; Crow, MJ; Wax, A; Izatt, JA
MLA Citation
Skala, MC, Crow, MJ, Wax, A, and Izatt, JA. "Photothermal optical coherence tomography for molecular imaging." January 1, 2011.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Real-time quantitative phase and dual-channel fluorescence microscopy for studying cellular and biomolecular dynamics

We have developed a microscope that simultaneously captures quantitative phase measurements and two distinct fluorescence images on a single camera. This microscope is an effective tool for investigating cellular dynamics with molecular specificity. © 2011 Optical Society of America.

Authors
Rinehart, MT; Shaked, NT; Satterwhite, L; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, Satterwhite, L, and Wax, A. "Real-time quantitative phase and dual-channel fluorescence microscopy for studying cellular and biomolecular dynamics." January 1, 2011.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Whole-cell analysis of cardiomyocytes with combined quantitative phase and two-channel fluorescence microscopy

We have developed a novel microscope combining quantitative phase and fluorescence microscopy to perform quantitative analysis of dynamic cardiomyocyte contraction. Phase-based parameters are informed by molecular specificity of fluorescence images. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Rinehart, MT; Shaked, NT; Satterwhite, L; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, Satterwhite, L, and Wax, A. "Whole-cell analysis of cardiomyocytes with combined quantitative phase and two-channel fluorescence microscopy." January 1, 2011.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Spectral-domain differential interference contrast microscopy

We present a novel imaging technique, termed spectral-domain DIC microscopy, for high-resolution quantitative measurement of optical pathlength gradients. Imaging of resolution target and live cardiomyocytes were demonstrated with 36pm resolution. © 2011 Optical Society of America.

Authors
Zhu, Y; Shaked, NT; Satterwhite, LL; Wax, A
MLA Citation
Zhu, Y, Shaked, NT, Satterwhite, LL, and Wax, A. "Spectral-domain differential interference contrast microscopy." January 1, 2011.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology

Authors
Zhu, Y; Terry, NG; Woosley, JT; Shaheen, NJ; Wax, A
MLA Citation
Zhu, Y, Terry, NG, Woosley, JT, Shaheen, NJ, and Wax, A. "Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology." JOURNAL OF BIOMEDICAL OPTICS 16.1 (January 2011).
Source
wos-lite
Published In
Journal of Biomedical Optics
Volume
16
Issue
1
Publish Date
2011
DOI
10.1117/1.35201301

Plasmonic flow cytometry by immunolabeled nanorods.

Fluorescence-based flow cytometry measures multiple cellular characteristics, including levels of receptor expression, by assessing the fluorescence intensity from a population of cells whose cell surface receptors are bound by a fluorescently labeled antibody or ligand for that receptor. Functionalized noble metal nanoparticles provide a complementary method of receptor labeling based on plasmonics for population analysis by flow cytometry. The potential benefits of using plasmonic nanoparticles to label cell surface receptors in flow cytometry include scattering intensity from a single particle that is equivalent to fluorescence intensity of 10⁵ fluorescein molecules, biocompatibility and low cytotoxicity, and nonquenching optical properties. The large spectral tunability of nanorods also provides convenient access to plasmonic markers with peak surface plasmon resonances ranging from 600 to 2,200 nm, unlike gold nanosphere markers that are limited to visible wavelengths. Gold nanorod-based plasmonic flow cytometry is demonstrated herein by comparing the scattering of cells bound to anti-epidermal growth factor receptor (EGFR)-conjugated nanorods to the emission of cells bound to anti-EGFR-conjugated fluorescent labels. EGFR-expressing cells exhibited a statistically significant six-fold increase in scattering when labeled with anti-EGFR-conjugated nanorods compared with labeling with IgG1-conjugated nanorods. Large scattering intensities were observed despite using a 1,000-fold lower concentration of nanorod-conjugated antibody relative to the fluorescently labeled antibody.

Authors
Crow, MJ; Marinakos, SM; Cook, JM; Chilkoti, A; Wax, A
MLA Citation
Crow, MJ, Marinakos, SM, Cook, JM, Chilkoti, A, and Wax, A. "Plasmonic flow cytometry by immunolabeled nanorods." Cytometry A 79.1 (January 2011): 57-65.
PMID
21182183
Source
pubmed
Published In
Cytometry
Volume
79
Issue
1
Publish Date
2011
Start Page
57
End Page
65
DOI
10.1002/cyto.a.20994

Photothermal optical coherence tomography for molecular imaging

Authors
Skala, MC; Crow, MJ; Wax, A; Izatt, JA
MLA Citation
Skala, MC, Crow, MJ, Wax, A, and Izatt, JA. "Photothermal optical coherence tomography for molecular imaging." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Whole-cell analysis of cardiomyocytes with combined quantitative phase and two-channel fluorescence microscopy

Authors
Rinehart, MT; Shaked, NT; Satterwhite, L; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, Satterwhite, L, and Wax, A. "Whole-cell analysis of cardiomyocytes with combined quantitative phase and two-channel fluorescence microscopy." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Spectral-domain differential interference contrast microscopy

Authors
Zhu, Y; Shaked, NT; Satterwhite, LL; Wax, A
MLA Citation
Zhu, Y, Shaked, NT, Satterwhite, LL, and Wax, A. "Spectral-domain differential interference contrast microscopy." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Real-time quantitative phase and dual-channel fluorescence microscopy for studying cellular and biomolecular dynamics

Authors
Rinehart, MT; Shaked, NT; Satterwhite, L; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, Satterwhite, L, and Wax, A. "Real-time quantitative phase and dual-channel fluorescence microscopy for studying cellular and biomolecular dynamics." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Photothermal optical coherence tomography for molecular imaging

Molecular imaging using Photothermal Optical Coherence Tomography (OCT) was demonstrated with antibody-conjugated gold nanoparticles in phantoms and three-dimensional tissue constructs. Cells over-expressing the epidermal growth factor receptor (EGFR) were differentiated from under-expressing cells in three-dimensions. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Skala, MC; Crow, MJ; Wax, A; Izatt, JA
MLA Citation
Skala, MC, Crow, MJ, Wax, A, and Izatt, JA. "Photothermal optical coherence tomography for molecular imaging." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Whole-cell analysis of cardiomyocytes with combined quantitative phase and two-channel fluorescence microscopy

We have developed a novel microscope combining quantitative phase and fluorescence microscopy to perform quantitative analysis of dynamic cardiomyocyte contraction. Phase-based parameters are informed by molecular specificity of fluorescence images. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Rinehart, MT; Shaked, NT; Satterwhite, L; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, Satterwhite, L, and Wax, A. "Whole-cell analysis of cardiomyocytes with combined quantitative phase and two-channel fluorescence microscopy." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Real-time quantitative phase and dual-channel fluorescence microscopy for studying cellular and biomolecular dynamics

We have developed a microscope that simultaneously captures quantitative phase measurements and two distinct fluorescence images on a single camera. This microscope is an effective tool for investigating cellular dynamics with molecular specificity. © 2011 Optical Society of America.

Authors
Rinehart, MT; Shaked, NT; Satterwhite, L; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, Satterwhite, L, and Wax, A. "Real-time quantitative phase and dual-channel fluorescence microscopy for studying cellular and biomolecular dynamics." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Spectral-domain differential interference contrast microscopy

We present a novel imaging technique, termed spectral-domain DIC microscopy, for high-resolution quantitative measurement of optical pathlength gradients. Imaging of resolution target and live cardiomyocytes were demonstrated with 36pm resolution. © 2011 Optical Society of America.

Authors
Zhu, Y; Shaked, NT; Satterwhite, LL; Wax, A
MLA Citation
Zhu, Y, Shaked, NT, Satterwhite, LL, and Wax, A. "Spectral-domain differential interference contrast microscopy." Optics InfoBase Conference Papers (2011).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Multimodal optical detection of intravaginal microbicide gel coating thickness distribution

A clinical optical imaging probe incorporating simultaneous fluorescence and low coherence interferometry (LCI) imaging optics was developed. A clinical study was performed to compare LCI and fluorimetry in measuring intravaginal microbicide gel coating thickness distribution. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Drake, T; Peters, J; Henderson, M; DeSoto, M; Katz, D; Wax, A
MLA Citation
Drake, T, Peters, J, Henderson, M, DeSoto, M, Katz, D, and Wax, A. "Multimodal optical detection of intravaginal microbicide gel coating thickness distribution." Optics InfoBase Conference Papers (2011).
Source
scival
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Spectroscopic optical coherence tomography for quantitative molecular imaging

Advances in spectroscopic OCT have allowed for quantitative analysis of endogenous contrast agents. Here, we will use SOCT to achieve quantitative molecular imaging using various exogenous contrast agents spanning the visible region of the spectrum. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Robles, FE; Wax, A
MLA Citation
Robles, FE, and Wax, A. "Spectroscopic optical coherence tomography for quantitative molecular imaging." Optics InfoBase Conference Papers (2011).
Source
scival
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Multimodal optical detection of intravaginal microbicide gel coating thickness distribution

A clinical optical imaging probe incorporating simultaneous fluorescence and low coherence interferometry (LCI) imaging optics was developed. A clinical study was performed to compare LCI and fluorimetry in measuring intravaginal microbicide gel coating thickness distribution. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Drake, T; Peters, J; Henderson, M; DeSoto, M; Katz, D; Wax, A
MLA Citation
Drake, T, Peters, J, Henderson, M, DeSoto, M, Katz, D, and Wax, A. "Multimodal optical detection of intravaginal microbicide gel coating thickness distribution." Optics InfoBase Conference Papers (2011).
Source
scival
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Spectroscopic optical coherence tomography for quantitative molecular imaging

Advances in spectroscopic OCT have allowed for quantitative analysis of endogenous contrast agents. Here, we will use SOCT to achieve quantitative molecular imaging using various exogenous contrast agents spanning the visible region of the spectrum. © 2011 OSA: BODA/NTM/OMP/OTA.

Authors
Robles, FE; Wax, A
MLA Citation
Robles, FE, and Wax, A. "Spectroscopic optical coherence tomography for quantitative molecular imaging." Optics InfoBase Conference Papers (2011).
Source
scival
Published In
Optics InfoBase Conference Papers
Publish Date
2011

Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy.

Quantitative phase microscopy is applied to image temporal changes in the refractive index (RI) distributions of solutions created by microbicidal films undergoing hydration. We present a novel method of using an engineered polydimethylsiloxane structure as a static phase reference to facilitate calibration of the absolute RI across the entire field. We present a study of dynamic structural changes in microbicidal films during hydration and subsequent dissolution. With assumptions about the smoothness of the phase changes induced by these films, we calculate absolute changes in the percentage of film in regions across the field of view.

Authors
Rinehart, MT; Drake, TK; Robles, FE; Rohan, LC; Katz, D; Wax, A
MLA Citation
Rinehart, MT, Drake, TK, Robles, FE, Rohan, LC, Katz, D, and Wax, A. "Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy." Journal of biomedical optics 16.12 (2011): 120510--.
PMID
22191912
Source
scival
Published In
Journal of Biomedical Optics
Volume
16
Issue
12
Publish Date
2011
Start Page
120510-
DOI
10.1117/1.3665439

Whole cell imaging based on wide-field interferometric phase microscopy and its application to cardiomyocytes

Whole cell imaging is a novel technique using which the time-dependent quantitative phase profiles of live unstained biological cells are analyzed numerically to learn on the cell functionally. Dynamic phase profiles of the sample are first acquired by wide-field digital interferometry (WFDI), a quantitative holographic approach, without the need for scanning or using exogenous contrast agents. The resulting phase profiles are proportional to the multiplication between the cell thickness profile and its integral refractive index profile. However, many morphological parameters, including cell volume and cell force distribution, are based on the cell thickness profile, rather than on its WFDI phase profile. For cells with heterogeneous refractive index structure, more than a single exposure is typically needed to decouple thickness from integral refractive index using the phase profile, with the risk of losing transient acquisition. The presented whole-cell-imaging approach show that the WFDI phase profiles are useful for numerically analyzing cells even in cases where decoupling of thickness and integral refractive index is not possible or desired. We thus define new numerical parameters that directly utilize the WFDI phase profile and demonstrate their usefulness for characterizing contracting cardiomyocytes, cells with complex and highly-dynamic refractive-index structure. © 2011 SPIE.

Authors
Shaked, NT; Satterwhite, LL; Bursac, N; Wax, A
MLA Citation
Shaked, NT, Satterwhite, LL, Bursac, N, and Wax, A. "Whole cell imaging based on wide-field interferometric phase microscopy and its application to cardiomyocytes." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7904 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7904
Publish Date
2011
DOI
10.1117/12.874224

Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles

This work presents simultaneous imaging and detection of three types of cell receptors using three types of plasmonic nanoparticles. The size, shape, and composition-dependent scattering profiles of these particles allow for a system of multiple distinct molecular markers using a single optical source. With this goal in mind, a system of tags consisting of anti-EGFR gold nanorods, anti-IGF1R silver nanospheres, and anti-HER-2 gold nanospheres was developed for monitoring the expression of three commonly overexpressed receptors in cancer cells. These labels were chosen because they each scatter strongly in a distinct spectral window. A hyperspectral dark-field microscope was developed to record the scattering spectra of cells labeled with these molecular tags. The ability to monitor multiple tags simultaneously may lead to applications such as profiling the immunophenotype of cell lines and gaining better knowledge of receptor signaling pathways. Single, dual, and triple tag experiments were performed to analyze the specificity of the nanoparticle tags as well as their effect on one another. While distinct resonance peaks in these studies show the ability to characterize cell lines using conjugated nanoparticles, shifts in these peaks also indicate changes in the cellular dielectric environment which may not be distinct from plasmon coupling between nanoparticles bound to proximal receptors. © 2011 SPIE.

Authors
Crow, MJ; Seekell, K; Marinakos, S; Ostrander, J; Chilkoti, A; Wax, AP
MLA Citation
Crow, MJ, Seekell, K, Marinakos, S, Ostrander, J, Chilkoti, A, and Wax, AP. "Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7911 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7911
Publish Date
2011
DOI
10.1117/12.874093

Molecular imaging true-colour spectroscopic optical coherence tomography

Molecular imaging holds a pivotal role in medicine due to its ability to provide invaluable insight into disease mechanisms at molecular and cellular levels. To this end, various techniques have been developed for molecular imaging, each with its own advantages and disadvantages1-4. For example, fluorescence imaging achieves micrometre-scale resolution, but has low penetration depths and is mostly limited to exogenous agents. Here, we demonstrate molecular imaging of endogenous and exogenous chromophores using a novel form of spectroscopic optical coherence tomography. Our approach consists of using a wide spectral bandwidth laser source centred in the visible spectrum, thereby allowing facile assessment of haemoglobin oxygen levels, providing contrast from readily available absorbers, and enabling true-colour representation of samples. This approach provides high spectral fidelity while imaging at the micrometre scale in three dimensions. Molecular imaging true-colour spectroscopic optical coherence tomography (METRiCS OCT) has significant implications for many biomedical applications including ophthalmology, early cancer detection, and understanding fundamental disease mechanisms such as hypoxia and angiogenesis. © 2011 Macmillan Publishers Limited. All rights reserved.

Authors
Robles, FE; Wilson, C; Grant, G; Wax, A
MLA Citation
Robles, FE, Wilson, C, Grant, G, and Wax, A. "Molecular imaging true-colour spectroscopic optical coherence tomography." Nature Photonics 5.12 (2011): 744-747.
PMID
23144652
Source
scival
Published In
Nature Photonics
Volume
5
Issue
12
Publish Date
2011
Start Page
744
End Page
747
DOI
10.1038/nphoton.2011.257

Design and validation of a multiplexed low coherence interferometry instrument for in vivo clinical measurement of microbicide gel thickness distribution

We present a multiplexed, Fourier-domain low coherence interferometry (mLCI) instrument for in vivo measurement of intravaginal microbicide gel coating thickness distribution over the surface of the vaginal epithelium. The mLCI instrument uses multiple delivery fibers to acquire depth resolved reflection profiles across large scanned tissue areas. Here mLCI has been adapted into an endoscopic system with a custom imaging module for simultaneous, co-registered measurements with fluorimetric scans of the same surface. The resolution, optical signal-tonoise, and cross-talk of the mLCI instrument are characterized to evaluate performance. Validation measurements of gel thickness are made using a calibration socket. Initial results from a clinical study are presented to show the in vivo capability of the dual-modality system for assessing the distribution of microbicide gel vehicles in the lower human female reproductive tract. © 2011 Optical Society of America.

Authors
Drake, TK; DeSoto, MG; Peters, JJ; Henderson, MH; Murtha, AP; Katz, DF; Wax, A
MLA Citation
Drake, TK, DeSoto, MG, Peters, JJ, Henderson, MH, Murtha, AP, Katz, DF, and Wax, A. "Design and validation of a multiplexed low coherence interferometry instrument for in vivo clinical measurement of microbicide gel thickness distribution." Biomedical Optics Express 2.10 (2011): 2850-2858.
PMID
22025989
Source
scival
Published In
Biomedical Optics Express
Volume
2
Issue
10
Publish Date
2011
Start Page
2850
End Page
2858
DOI
10.1364/BOE.2.002850

Simultaneous confocal fluorescence microscopy and optical coherence tomography for drug distribution and tissue integrity assessment

The effectiveness of microbicidal gels, topical products developed to prevent infection by sexually transmitted diseases including HIV/AIDS, is governed by extent of gel coverage, pharmacokinetics of active pharmaceutical ingredients (APIs), and integrity of vaginal epithelium. While biopsies provide localized information about drug delivery and tissue structure, in vivo measurements are preferable in providing objective data on API and gel coating distribution as well as tissue integrity. We are developing a system combining confocal fluorescence microscopy with optical coherence tomography (OCT) to simultaneously measure local concentrations and diffusion coefficients of APIs during transport from microbicidal gels into tissue, while assessing tissue integrity. The confocal module acquires 2-D images of fluorescent APIs multiple times per second allowing analysis of lateral diffusion kinetics. The custom Fourier domain OCT module has a maximum a-scan rate of 54 kHz and provides depth-resolved tissue integrity information coregistered with the confocal fluorescence measurements. The combined system is validated by imaging phantoms with a surrogate fluorophore. Time-resolved API concentration measured at fixed depths is analyzed for diffusion kinetics. This multimodal system will eventually be implemented in vivo for objective evaluation of microbicide product performance. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Authors
Rinehart, MT; Lacroix, J; Henderson, M; Katz, D; Wax, A
MLA Citation
Rinehart, MT, Lacroix, J, Henderson, M, Katz, D, and Wax, A. "Simultaneous confocal fluorescence microscopy and optical coherence tomography for drug distribution and tissue integrity assessment." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7890 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7890
Publish Date
2011
DOI
10.1117/12.874986

Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles

The dimerization of receptors on the cell membrane is an important step in the activation of cell signaling pathways. Several methods exist for observing receptor dimerization, including coimmunoprecipitation, chemical cross-linking, and fluorescence resonance energy transfer (FRET). These techniques are limited in that only FRET is appropriate for live cells, but even that method suffers from photobleaching and bleed-through effects. In this study, we implement an alternative method for the targeting of HER-2 homodimer formation based on the plasmonic coupling of gold nanoparticles functionalized with HER-2 Ab. In the presented studies, SK-BR-3 cells, known to overexpress HER-2, are labeled with these nanoparticles and receptor colocalization is observed using plasmonic coupling. HER-2 targeted nanoparticles bound to these cells exhibit a peak resonance that is significantly red-shifted relative to those bound to similar receptors on A549 cells, which have significantly lower levels of HER-2 expression. This significant red shift indicates plasmonic coupling is occurring and points to a new avenue for assessing dimerization by monitoring their colocalization. To determine that dimerization is occurring, the refractive index of the nanoenvironment of the labels is assessed using a theoretical analysis based on the Mie coated sphere model. The results indicate scattering by single, isolated nanoparticles for the low HER-2 expressing A549 cell line, but the scattering observed for the HER-2 overexpressing SK-BR-3 cell line may only be explained by plasmonic-coupling of proximal nanoparticle pairs. To validate the conformation of nanoparticles bound to HER-2 receptors undergoing dimerization, discrete dipole approximation (DDA) models are used to assess spectra of scattering by coupled nanoparticles. Comparison of the experimental results with theoretical models indicates that NP dimers are formed for the labeling of SK-BR-3 cells, suggesting that receptor dimerization has been observed. © 2011 American Chemical Society.

Authors
Crow, MJ; Seekell, K; Ostrander, JH; Wax, A
MLA Citation
Crow, MJ, Seekell, K, Ostrander, JH, and Wax, A. "Monitoring of receptor dimerization using plasmonic coupling of gold nanoparticles." ACS Nano 5.11 (2011): 8532-8540.
PMID
21999459
Source
scival
Published In
ACS Nano
Volume
5
Issue
11
Publish Date
2011
Start Page
8532
End Page
8540
DOI
10.1021/nn201451c

Angle-resolved low coherence interferometry for detection of dysplasia in Barrett's esophagus

Authors
Wax, A; Terry, NG; Dellon, ES; Shaheen, NJ
MLA Citation
Wax, A, Terry, NG, Dellon, ES, and Shaheen, NJ. "Angle-resolved low coherence interferometry for detection of dysplasia in Barrett's esophagus." Gastroenterology 141.2 (2011): 443-447.e2.
PMID
21703265
Source
scival
Published In
Gastroenterology
Volume
141
Issue
2
Publish Date
2011
Start Page
443
End Page
447.e2
DOI
10.1053/j.gastro.2011.06.020

Polarization mapping of nanoparticle plasmonic coupling

We propose the use of polarization mapping as a tool to better separate the effects of plasmonic coupling from the local refractive index for molecular imaging and biosensing using gold nanoparticles. Polarization mapping allows identification of the orthogonal excitation mode when the particle dimer orientation is unknown, as may be the case when using plasmonic nanoparticles for cell labeling. This information can be used to sense relative changes in the dielectric environment, or for absolute dielectric sensing with additional a priori interparticle distance information. First, the theoretical scattering by nanoparticle pairs is modeled under parallel and orthogonal polarization orientations and increasing interparticle separation. Second, polarization mapping of substrate bound nanoparticles using dark-field microspectroscopy is investigated as a method to isolate the individual plasmonic coupling modes associated with a pair of nanoparticles without reorientation of the sample. The results of this study provide useful insight toward potential avenues for monitoring distances using plasmonic nanoparticles and sensing the local refractive index using nanoparticle pairs when the pair orientation is not known, as may be the case when using nanoparticles for cell receptor labeling. © 2011 Optical Society of America.

Authors
Crow, MJ; Seekell, K; Wax, A
MLA Citation
Crow, MJ, Seekell, K, and Wax, A. "Polarization mapping of nanoparticle plasmonic coupling." Optics Letters 36.5 (2011): 757-759.
PMID
21368973
Source
scival
Published In
Optics Letters
Volume
36
Issue
5
Publish Date
2011
Start Page
757
End Page
759
DOI
10.1364/OL.36.000757

Imaging beyond the ballistic limit in coherence imaging using multiply scattered light

We present an imaging system based on low coherence interferometric detection of multiply scattered light for extended depth imaging into highly scattering media. By incorporating angle-resolved detection, coherence imaging with multiply scattered photons is shown to be both feasible and potentially superior to existing techniques for performing time-resolved measurements of scattered light. Imaging is demonstrated through nearly 100 mean free paths of scattering phantom in a single-ended geometry. The resolution and imaging contrast are compared to those obtained with conventional OCT systems which chiefly detect singly scattered light. ©2011 Optical Society of America.

Authors
Giacomelli, MG; Wax, A
MLA Citation
Giacomelli, MG, and Wax, A. "Imaging beyond the ballistic limit in coherence imaging using multiply scattered light." Optics Express 19.5 (2011): 4268-4279.
PMID
21369257
Source
scival
Published In
Optics express
Volume
19
Issue
5
Publish Date
2011
Start Page
4268
End Page
4279
DOI
10.1364/OE.19.004268

Nuclear morphology measurements with angle-resolved low coherence interferometry for application to cell biology and early cancer detection

The study of intact, living cells using non-invasive optical spectroscopic methods offers the opportunity to assess cellular structure and organization in a way that is not possible with commonly used cell biology imaging techniques. We have developed a novel spectroscopic technique for diagnosing disease at the cellular level based on using low-coherence interferometry (LCI) to detect the angular distribution of scattered light. Angle-resolved LCI (a/LCI) combines the ability of LCI to isolate scattering from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales. In application to examining cellular structure, a/LCI enables quantitative measurements of changes in the size and texture of cell nuclei. These quantitative measurements are characteristic of different pathological states. The capabilities of a/LCI were demonstrated using a clinical system that can be applied in endoscopic surveillance of esophageal tissue, producing high sensitivity and specificity for detecting dysplastic tissues in vivo. Experiments with in vitro cell samples also show the utility of a/LCI in observing structural changes due to environmental stimuli as well as detecting apoptosis due to chemotherapeutic agents. © 2011-IOS Press and the authors. All rights reserved.

Authors
Wax, A; Chalut, KJ
MLA Citation
Wax, A, and Chalut, KJ. "Nuclear morphology measurements with angle-resolved low coherence interferometry for application to cell biology and early cancer detection." Analytical Cellular Pathology 34.5 (2011): 207-222.
PMID
21988885
Source
scival
Published In
Cellular Oncology
Volume
34
Issue
5
Publish Date
2011
Start Page
207
End Page
222
DOI
10.3233/ACP-2011-0017

Quantitative phase microscopy of biological cell dynamics by wide-field digital interferometry

Interferometric phase measurements of wide-field images of biological cells provide a quantitative tool for cell biology, as well as for medical diagnosis and monitoring. Visualizing rapid dynamic cell phenomena by interferometric phase microscopy can be performed at very fast rates of up to several thousands of full frames per second, while retaining high resolution and contrast to enable measurements of fine cellular features. With this approach, no special sample preparation, staining, or fluorescent labeling is required, and the resulting phase profiles yield the optical path delay profile of the cell with sub-nanometer accuracy. In spite of these unique advantages, interferometric phase microscopy has not been widely applied for recording the dynamic behavior of live cells compared to other traditional phase microscopy methods such as phase contrast and differential interference contrast (DIC) microscopy, which are label free but inherently qualitative. Recent developments in the field of interferometric phase microscopy are likely to result in a change in this situation in the near future. Through careful consideration of the capabilities and limitations of interferometric phase microscopy, important new contributions in the fields of cell biology and biomedicine will be realized. This chapter presents the current state of the art of interferometric phase microscopy of biological cell dynamics, the open questions in this area, and specific solutions developed in our laboratory. © Springer-Verlag Berlin Heidelberg 2011.

Authors
Shaked, NT; Rinehart, MT; Wax, A
MLA Citation
Shaked, NT, Rinehart, MT, and Wax, A. "Quantitative phase microscopy of biological cell dynamics by wide-field digital interferometry." Springer Series in Surface Sciences 46.1 (2011): 169-198.
Source
scival
Published In
Springer Series in Surface Sciences
Volume
46
Issue
1
Publish Date
2011
Start Page
169
End Page
198
DOI
10.1007/978-3-642-15813-1_7

Coherent detection of diffusely scattered light for extending depth using multiply scattered low coherence interferometry

Interferometric based imaging has a number of advantages over direct detection of photons, including very high time resolution, shot noise limited sensitivity, and reasonable cost. In spite of these advantages, diffuse optical techniques have almost exclusively used direct detection. In order to explore the feasibility of interferometrically detected multiply scattered light, we constructed a multiply scattered low coherence interferometry (MS/LCI) system. Using angle resolved detection and a novel illumination scheme, we demonstrate direct imaging through nearly 94 mean free scattering paths. © 2011 SPIE.

Authors
Giacomelli, M; Wax, A
MLA Citation
Giacomelli, M, and Wax, A. "Coherent detection of diffusely scattered light for extending depth using multiply scattered low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7896 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7896
Publish Date
2011
DOI
10.1117/12.874089

Determining size, shape, and orientation of non-spherical scatterers using the fiber optic interferometric two-dimensional scattering (FITS) system

Angle-resolved scattering measurements have shown promise as a method of detecting neoplasia and analyzing cellular structure. Recently we have developed new systems for interferometric measurement of two-dimensional, depth resolved scattered fields with excellent depth resolution and polarization sensitivity. We present inverse analysis of oriented ensembles of micro-spheroidal phantoms and cells showing sub-wavelength accuracy in size and shape determination, and additionally precise estimates of scatterer orientation. Finally we show that inverse fits provided are essentially free of multiple solutions over a wide range of possible scatterer sizes and shapes. © 2011 SPIE.

Authors
Giacomelli, M; Zhu, Y; Lee, J; Wax, A
MLA Citation
Giacomelli, M, Zhu, Y, Lee, J, and Wax, A. "Determining size, shape, and orientation of non-spherical scatterers using the fiber optic interferometric two-dimensional scattering (FITS) system." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7907 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7907
Publish Date
2011
DOI
10.1117/12.874081

Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology

We present a novel Fourier-domain angle-resolved low-coherence interferometry (a /LCI) fiber probe designed for in vivo clinical application in gastrointestinal endoscopy. The a/LCI technique measures the depth-resolved angular scattering distribution to determine the size distribution and optical density of cell nuclei for assessing the health of epithelial tissues. Clinical application is enabled by an endoscopic fiber-optic probe that employs a 2.3-m-long coherent fiber bundle and is compatible with the standard 2.8-mm-diam biopsy channel of a gastroscope. The probe allows for real-time data acquisition by collecting the scattering from multiple angles in parallel, enabled by the Fourier domain approach. The performance of the probe is characterized through measurement of critical parameters. The depth-resolved sizing capability of the system is demonstrated using single- and double-layer microsphere phantoms with subwavelength sizing precision and accuracy achieved. Initial results from a clinical feasibility test are also presented to show in vivo application in the human esophagus. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Authors
Zhu, Y; Terry, NG; Woosley, JT; Shaheen, NJ; Wax, A
MLA Citation
Zhu, Y, Terry, NG, Woosley, JT, Shaheen, NJ, and Wax, A. "Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology." Journal of Biomedical Optics 16.1 (2011).
PMID
21280890
Source
scival
Published In
Journal of Biomedical Optics
Volume
16
Issue
1
Publish Date
2011
DOI
10.1117/1.3520130

Fourier domain low coherence interferometry for detection of early colorectal cancer development in the AOM rat model

We present Fourier domain low coherence interferometry (fLCI) applied to the detection of preneoplastic changes in the colon using the ex-vivo azoxymethane (AOM) rat carcinogenesis model. fLCI measures depth resolved spectral oscillations, also known as local oscillations, resulting from coherent fields induced by the scattering of cell nuclei. The depth resolution of fLCI permits nuclear morphology measurements within thick tissues, making the technique sensitive to the earliest stages of precancerous development. To achieve depth resolved spectroscopic analysis, we use the dual window method, which obtains simultaneously high spectral and depth resolution and yields access to the local oscillations. The results show highly statistically significant differences between the AOM-treated and control group samples. Further, the results suggest that fLCI may be used to detect the field effect of carcinogenesis, in addition to identifying specific areas where more advanced neoplastic development has occurred. © 2011 SPIE.

Authors
Robles, FE; Zhu, Y; Lee, J; Sharma, S; Wax, A
MLA Citation
Robles, FE, Zhu, Y, Lee, J, Sharma, S, and Wax, A. "Fourier domain low coherence interferometry for detection of early colorectal cancer development in the AOM rat model." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7907 (2011).
Source
scival
Published In
Proceedings of SPIE
Volume
7907
Publish Date
2011
DOI
10.1117/12.872929

Detection of dysplasia in barrett's esophagus with in vivo depth-resolved nuclear morphology measurements

Background & Aims: Patients with Barrett's esophagus (BE) show increased risk of developing esophageal adenocarcinoma and are routinely examined using upper endoscopy with biopsy to detect neoplastic changes. Angle-resolved low coherence interferometry (a/LCI) uses in vivo depth-resolved nuclear morphology measurements to detect dysplasia. We assessed the clinical utility of a/LCI in the endoscopic surveillance of patients with BE. Methods: Consecutive patients undergoing routine surveillance upper endoscopy for BE were recruited at 2 endoscopy centers. A novel, endoscope-compatible a/LCI system measured the mean diameter and refractive index of cell nuclei in esophageal epithelium at 172 biopsy sites in 46 patients. At each site, an a/LCI measurement was correlated with a concurrent endoscopic biopsy specimen. Each biopsy specimen was assessed histologically and classified as normal, nondysplastic BE, indeterminate for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). The a/LCI data from multiple depths were analyzed to evaluate its ability to differentiate dysplastic from nondysplastic tissue. Results: Pathology characterized 5 of the scanned sites as HGD, 8 as LGD, 75 as nondysplastic BE, 70 as normal tissue types, and 14 as indeterminate for dysplasia. The a/LCI nuclear size measurements separated dysplastic from nondysplastic tissue at a statistically significant (P < .001) level for the tissue segment 200 to 300 μm beneath the surface with an accuracy of 86% (147/172). A receiver operator characteristic analysis indicated an area under the curve of 0.91, and an optimized decision point gave 100% (13/13) sensitivity and 84% (134/159) specificity. Conclusions:: These preliminary data suggest a/LCI is accurate in detecting dysplasia in vivo in patients with BE. © 2011 AGA Institute.

Authors
Terry, NG; Zhu, Y; Rinehart, MT; Brown, WJ; Gebhart, SC; Bright, S; Carretta, E; Ziefle, CG; Panjehpour, M; Galanko, J; Madanick, RD; Dellon, ES; Trembath, D; Bennett, A; Goldblum, JR; Overholt, BF; Woosley, JT; Shaheen, NJ; Wax, A
MLA Citation
Terry, NG, Zhu, Y, Rinehart, MT, Brown, WJ, Gebhart, SC, Bright, S, Carretta, E, Ziefle, CG, Panjehpour, M, Galanko, J, Madanick, RD, Dellon, ES, Trembath, D, Bennett, A, Goldblum, JR, Overholt, BF, Woosley, JT, Shaheen, NJ, and Wax, A. "Detection of dysplasia in barrett's esophagus with in vivo depth-resolved nuclear morphology measurements." Gastroenterology 140.1 (2011): 42-50.
PMID
20854820
Source
scival
Published In
Gastroenterology
Volume
140
Issue
1
Publish Date
2011
Start Page
42
End Page
50
DOI
10.1053/j.gastro.2010.09.008

Development of angle-resolved low coherence interferometry for clinical detection of dysplasia

This review covers the development of angle-resolved low coherence interferometry (a/LCI) from initial development through clinical application. In the first applications, the approach used a time-domain interferometry scheme and was validated using animal models of carcinogenesis to assess the feasibility of detecting dysplasia in situ. Further development of the approach led to Fourier-domain interferometry schemes with higher throughput and endoscope-compatible probes to enable clinical application. These later implementations have been applied to clinical studies of dysplasia in Barrett′s esophagus tissues, a metaplastic tissue type that is associated with an increased risk of esophageal adenocarcinoma. As an alternative to systematic biopsy, the a/LCI approach offers high sensitivity and specificity for detecting dysplasia in these tissues while avoiding the need for tissue removal or exogenous contrast agents. Here, the various implementations of a/LCI are discussed and the results of the preliminary animal experiments and ex vivo human tissue studies are reviewed. A review of a recent in vivo clinical study is also presented.

Authors
Zhu, Y; Terry, N; Wax, A
MLA Citation
Zhu, Y, Terry, N, and Wax, A. "Development of angle-resolved low coherence interferometry for clinical detection of dysplasia." Journal of Carcinogenesis 10 (2011).
PMID
21886457
Source
scival
Published In
Journal of Carcinogenesis
Volume
10
Publish Date
2011
DOI
10.4103/1477-3163.83935

Preface

Authors
Ferraro, P; Wax, AP; Zalevsky, Z
MLA Citation
Ferraro, P, Wax, AP, and Zalevsky, Z. "Preface." Springer Series in Surface Sciences 46.1 (2011): V-VI.
Source
scival
Published In
Springer Series in Surface Sciences
Volume
46
Issue
1
Publish Date
2011
Start Page
V
End Page
VI

Coherence imaging

This tutorial reviews coherence imaging approaches for biomedical applications. Subjects will include digital holography and optical coherence tomography modalities with an emphasis on basis of image formation, functional extensions and biological applications. © 2010 Optical Society of America.

Authors
Wax, A
MLA Citation
Wax, A. "Coherence imaging." Optics InfoBase Conference Papers (December 1, 2010).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2010

Detecting hemoglobin concentration using the dual window method for processing spectroscopic optical coherence tomography signals

We present a technique utilizing parallel frequency-domain OCT with the dual window method for processing SOCT signals to determine hemoglobin concentration. Preliminary data show our system's ability to quantitatively determine hemoglobin concentration from a phantom. ©2010 Optical Society of America.

Authors
Chowdhury, S; Robles, FE; Wax, A
MLA Citation
Chowdhury, S, Robles, FE, and Wax, A. "Detecting hemoglobin concentration using the dual window method for processing spectroscopic optical coherence tomography signals." Optics InfoBase Conference Papers (December 1, 2010).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2010

New directions in interferometric phase microscopy of biological cell dynamics

Interferometric phase microscopy has the potential of becoming a widely-used tool for quantitative measurements of biological cells. We introduce the current state of the art, the open questions, and solutions experimentally developed in our laboratory. © 2009 Optical Society of America.

Authors
Shaked, NT; Wax, A
MLA Citation
Shaked, NT, and Wax, A. "New directions in interferometric phase microscopy of biological cell dynamics." Optics InfoBase Conference Papers (December 1, 2010).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2010

Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy.

We apply wide-field interferometric microscopy techniques to acquire quantitative phase profiles of ventricular cardiomyocytes in vitro during their rapid contraction with high temporal and spatial resolution. The whole-cell phase profiles are analyzed to yield valuable quantitative parameters characterizing the cell dynamics, without the need to decouple thickness from refractive index differences. Our experimental results verify that these new parameters can be used with wide field interferometric microscopy to discriminate the modulation of cardiomyocyte contraction dynamics due to temperature variation. To demonstrate the necessity of the proposed numerical analysis for cardiomyocytes, we present confocal dual-fluorescence-channel microscopy results which show that the rapid motion of the cell organelles during contraction preclude assuming a homogenous refractive index over the entire cell contents, or using multiple-exposure or scanning microscopy.

Authors
Shaked, NT; Satterwhite, LL; Bursac, N; Wax, A
MLA Citation
Shaked, NT, Satterwhite, LL, Bursac, N, and Wax, A. "Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy. (Published online)" Biomed Opt Express 1.2 (August 23, 2010): 706-719.
Website
http://hdl.handle.net/10161/8427
PMID
21258502
Source
pubmed
Published In
Biomedical Optics Express
Volume
1
Issue
2
Publish Date
2010
Start Page
706
End Page
719
DOI
10.1364/BOE.1.000706

Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering.

We demonstrate accurate determination of the size and shape of spherical and spheroidal scatterers through inverse analysis of two-dimensional solid-angle and depth resolved backscattered light intensities. Intensity of scattered light is measured over a wide range of solid angles using a novel scanning fiber optic interferometer from both individual and ensembles of scatterers. T-matrix based inverse analysis of these two-dimensional angular measurements yields completely unique size and aspect ratio determinations with subwavelength precision over a large range of possible scatterer geometries.

Authors
Giacomelli, M; Zhu, Y; Lee, J; Wax, A
MLA Citation
Giacomelli, M, Zhu, Y, Lee, J, and Wax, A. "Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering." Opt Express 18.14 (July 5, 2010): 14616-14626.
PMID
20639947
Source
pubmed
Published In
Optics express
Volume
18
Issue
14
Publish Date
2010
Start Page
14616
End Page
14626

Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering

We demonstrate accurate determination of the size and shape of spherical and spheroidal scatterers through inverse analysis of twodimensional solid-angle and depth resolved backscattered light intensities. Intensity of scattered light is measured over a wide range of solid angles using a novel scanning fiber optic interferometer from both individual and ensembles of scatterers. T-matrix based inverse analysis of these twodimensional angular measurements yields completely unique size and aspect ratio determinations with subwavelength precision over a large range of possible scatterer geometries. ©2010 Optical Society of America.

Authors
Giacomelli, M; Zhu, Y; Lee, J; Wax, A
MLA Citation
Giacomelli, M, Zhu, Y, Lee, J, and Wax, A. "Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering." Optics Express 18.14 (July 5, 2010): 14616-14626.
Source
scopus
Published In
Optics express
Volume
18
Issue
14
Publish Date
2010
Start Page
14616
End Page
14626
DOI
10.1364/OE.18.14616

Reflective interferometric chamber for quantitative phase imaging of biological sample dynamics.

We introduce a new interferometric setup for single-exposure wide-field holographic phase imaging of highly dynamic biological samples. In this setup, the interferometric signal originates from a specially designed reflective interferometric chamber (InCh), creating an off-axis interferogram on the output plane of the system. The setup only requires the InCh and a simple reflection-mode two lens imaging system, without the need for additional optical elements such as gratings in the beam path. In addition, due to the close-to-common-path geometry of the setup, phase noise is greatly reduced. We experimentally compare the inherent phase stability of the system in ambient conditions to that of a conventional interferometer. We also demonstrate use of this system for wide-field quantitative phase imaging of two different highly dynamic, optically transparent biological samples: beating myocardial cells and moving unicellular microorganisms.

Authors
Shaked, NT; Zhu, Y; Badie, N; Bursac, N; Wax, A
MLA Citation
Shaked, NT, Zhu, Y, Badie, N, Bursac, N, and Wax, A. "Reflective interferometric chamber for quantitative phase imaging of biological sample dynamics." J Biomed Opt 15.3 (May 2010): 030503-. (Letter)
PMID
20614989
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
15
Issue
3
Publish Date
2010
Start Page
030503
DOI
10.1117/1.3420179

Deformation of stem cell nuclei by nanotopographical cues.

Cells sense cues in their surrounding microenvironment. These cues are converted into intracellular signals and transduced to the nucleus in order for the cell to respond and adapt its function. Within the nucleus, structural changes occur that ultimately lead to changes in the gene expression. In this study, we explore the structural changes of the nucleus of human mesenchymal stem cells as an effect of topographical cues. We use a controlled nanotopography to drive shape changes to the cell nucleus, and measure the changes with both fluorescence microscopy and a novel light scattering technique. The nucleus changes shape dramatically in response to the nanotopography, and in a manner dependent on the mechanical properties of the substrate. The kinetics of the nuclear deformation follows an unexpected trajectory. As opposed to a gradual shape change in response to the topography, once the cytoskeleton attains an aligned and elongation morphology on the time scale of several hours, the nucleus changes shape rapidly and intensely.

Authors
Chalut, KJ; Kulangara, K; Giacomelli, MG; Wax, A; Leong, KW
MLA Citation
Chalut, KJ, Kulangara, K, Giacomelli, MG, Wax, A, and Leong, KW. "Deformation of stem cell nuclei by nanotopographical cues." Soft Matter 6.8 (April 21, 2010): 1675-1681.
Website
http://hdl.handle.net/10161/4120
PMID
21297875
Source
pubmed
Published In
Soft Matter
Volume
6
Issue
8
Publish Date
2010
Start Page
1675
End Page
1681
DOI
10.1039/B921206J

Quantitative phase microscopy of articular chondrocyte dynamics by wide-field digital interferometry.

We experimentally implement label-free phase microscopy using wide-field digital interferometry (WFDI) techniques to retrieve quantitative volumetric data of articular chondrocyte dynamics. Using the scanless interferometric system, we visualize chondrocyte swelling and bursting induced by hypo-osmotic pressure. Reconstructed images are obtained by an efficient digital process. We use the resulting images to calculate quantitative temporal-spatial morphological parameters of the cell, with the observed dynamics limited only by the true frame rate of the camera. To show the utility of WFDI in recording articular chondrocyte dynamics, we also provide an experimental comparison of WFDI and differential interference contrast microscopy.

Authors
Shaked, NT; Finan, JD; Guilak, F; Wax, A
MLA Citation
Shaked, NT, Finan, JD, Guilak, F, and Wax, A. "Quantitative phase microscopy of articular chondrocyte dynamics by wide-field digital interferometry." J Biomed Opt 15.1 (January 2010): 010505-. (Letter)
PMID
20210420
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
15
Issue
1
Publish Date
2010
Start Page
010505
DOI
10.1117/1.3290242

Detection of early colorectal cancer development in the azoxymethane rat carcinogenesis model with fourier domain low coherence interferometry

Fourier domain low coherence interferometry (fLCI) is an emerging optical technique used to quantitatively assess cell nuclear morphology in tissue as a means of detecting early cancer development. In this work, we use the azoxymethane rat carcinogenesis model, a well characterized and established model for colon cancer research, to demonstrate the ability of fLCI to distinguish between normal and preneoplastic ex-vivo colon tissue. The results show highly statistically significant differences between the measured cell nuclear diameters of normal and azoxymethane-treated tissues, thus providing strong evidence that fLCI may be a powerful tool for non-invasive, quantitative detection of early changes associated with colorectal cancer development. © 2010 Optical Society of America.

Authors
Robles, FE; Zhu, Y; Lee, J; Sharma, S; Wax, A
MLA Citation
Robles, FE, Zhu, Y, Lee, J, Sharma, S, and Wax, A. "Detection of early colorectal cancer development in the azoxymethane rat carcinogenesis model with fourier domain low coherence interferometry." Biomedical Optics Express 1.2 (2010): 736-745.
PMID
21258505
Source
scival
Published In
Biomedical Optics Express
Volume
1
Issue
2
Publish Date
2010
Start Page
736
End Page
745
DOI
10.1364/BOE.1.000736

Simultaneous two-wavelength transmission quantitative phase microscopy with a color camera

We present a quantitative phase microscopy method that uses a Bayer mosaic color camera to simultaneously acquire off-axis interferograms in transmission mode at two distinct wavelengths. Wrapped phase information is processed using a two-wavelength algorithm to extend the range of the optical path delay measurements that can be detected using a single temporal acquisition. We experimentally demonstrate this technique by acquiring the phase profiles of optically clear microstructures without 2π ambiguities. In addition, the phase noise contribution arising from spectral channel crosstalk on the color camera is quantified. © 2010 Optical Society of America.

Authors
Rinehart, MT; Shaked, NT; Jenness, NJ; Clark, RL; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, Jenness, NJ, Clark, RL, and Wax, A. "Simultaneous two-wavelength transmission quantitative phase microscopy with a color camera." Optics Letters 35.15 (2010): 2612-2614.
Website
http://hdl.handle.net/10161/4224
PMID
20680075
Source
scival
Published In
Optics Letters
Volume
35
Issue
15
Publish Date
2010
Start Page
2612
End Page
2614
DOI
10.1364/OL.35.002612

Separating the scattering and absorption coefficients using the real and imaginary parts of the refractive index with low-coherence interferometry

We present an analytical method that yields die real and imaginary parts of the refractive index (RI) from lowcoherence interferometry measurements, leading to the separation of the scattering and absorption coefficients of turbid samples. The imaginary RI is measured using time-frequency analysis, with the real part obtained by analyzing the nonlinear phase induced by a sample. A derivation relating the real part of the RI to the nonlinear phase term of the signal is presented, along with measurements from scattering and nonscattering samples that exhibit absorption due to hemoglobin. © 2010 Optical Society of America.

Authors
Robles, FE; Wax, A
MLA Citation
Robles, FE, and Wax, A. "Separating the scattering and absorption coefficients using the real and imaginary parts of the refractive index with low-coherence interferometry." Optics Letters 35.17 (2010): 2843-2845.
Website
http://hdl.handle.net/10161/4225
PMID
20808343
Source
scival
Published In
Optics Letters
Volume
35
Issue
17
Publish Date
2010
Start Page
2843
End Page
2845
DOI
10.1364/OL.35.002843

Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnosticcs

Hemoglobin (Hb) concentration and oxygen saturation levels are important biomarkers for various diseases, including cancer. Here, we investigate the ability to measure these parameters for tissue using spectroscopic optical coherence tomography (SOCT). A parallel frequency domain OCT system is used with detection spanning the visible region of the spectrum (450 nm to 700 nm). Oxygenated and deoxygenated Hb absorbing phantoms are analyzed. The results show that Hb concentrations as low as 1.2 g/L at 1 mm can be retrieved indicating that both normal and cancerous tissue measurements may be obtained. However, measurement of oxygen saturation levels may not be achieved with this approach. © 2010 Optical Society of America.

Authors
Robles, FE; Chowdhury, S; Wax, A
MLA Citation
Robles, FE, Chowdhury, S, and Wax, A. "Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnosticcs." Biomedical Optics Express 1.1 (2010): 310-317.
PMID
21258468
Source
scival
Published In
Biomedical Optics Express
Volume
1
Issue
1
Publish Date
2010
Start Page
310
End Page
317
DOI
10.1364/BOE.1.000310

Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering

We demonstrate accurate determination of the size and shape of spherical and spheroidal scatterers through inverse analysis of twodimensional solid-angle and depth resolved backscattered light intensities. Intensity of scattered light is measured over a wide range of solid angles using a novel scanning fiber optic interferometer from both individual and ensembles of scatterers. T-matrix based inverse analysis of these twodimensional angular measurements yields completely unique size and aspect ratio determinations with subwavelength precision over a large range of possible scatterer geometries. ©2010 Optical Society of America.

Authors
Giacomelli, M; Zhu, Y; Lee, J; Wax, A
MLA Citation
Giacomelli, M, Zhu, Y, Lee, J, and Wax, A. "Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering." Optics Express 18.14 (2010): 14568-14576.
Website
http://hdl.handle.net/10161/4240
Source
scival
Published In
Optics express
Volume
18
Issue
14
Publish Date
2010
Start Page
14568
End Page
14576
DOI
10.1364/OE.18.014568

Review of the application of T-matrix calculations for determining the structure of cell nuclei with angle-resolved light scattering measurements

Biomedical applications of light scattering have traditionally relied on Mie theory as a theoretical basis for analyzing experimental measurements. While this approach is computationally accessible, the use of Mie theory cannot always account for the spheroidal nature of biological scatterers such as cell nuclei. As an alternative, we have developed light scattering codes based on the T-matrix formalism to analyze angle-resolved light scattering measurements. In this paper, we discuss the development of computer codes to create a database of scattering profiles, validation of the database using experimental measurements of tissue phantoms containing spheroidal scatterers, and recent applications of the approach to analyze the structure of cell nuclei. The reviewed studies show that while the T-matrix approach adds important information for some light scattering studies, the additional computational cost may not always be justified when compared to the Mie theory. © 2010 IEEE.

Authors
Giacomelli, MG; Chalut, KJ; Ostrander, JH; Wax, A
MLA Citation
Giacomelli, MG, Chalut, KJ, Ostrander, JH, and Wax, A. "Review of the application of T-matrix calculations for determining the structure of cell nuclei with angle-resolved light scattering measurements." IEEE Journal on Selected Topics in Quantum Electronics 16.4 (2010): 900-908.
Source
scival
Published In
IEEE Journal of Selected Topics in Quantum Electronics
Volume
16
Issue
4
Publish Date
2010
Start Page
900
End Page
908
DOI
10.1109/JSTQE.2009.2031984

Parallel on-axis holographic phase microscopy of biological cells and unicellular microorganism dynamics

We apply a wide-field quantitative phase microscopy technique based on parallel two-step phase-shifting on-axis interferometry to visualize live biological cells and microorganism dynamics. The parallel on-axis holographic approach is more efficient with camera spatial bandwidth consumption compared to previous off-axis approaches and thus can capture finer sample spatial details, given a limited spatial bandwidth of a specific digital camera. Additionally, due to the parallel acquisition mechanism, the approach is suitable for visualizing rapid dynamic processes, permitting an interferometric acquisition rate equal to the camera frame rate. The method is demonstrated experimentally through phase microscopy of neurons and unicellular microorganisms. © 2010 Optical Society of America.

Authors
Shaked, NT; Newpher, TM; Ehlers, MD; Wax, A
MLA Citation
Shaked, NT, Newpher, TM, Ehlers, MD, and Wax, A. "Parallel on-axis holographic phase microscopy of biological cells and unicellular microorganism dynamics." Applied Optics 49.15 (2010): 2872-2878.
Website
http://hdl.handle.net/10161/12464
PMID
20490249
Source
scival
Published In
Applied Optics
Volume
49
Issue
15
Publish Date
2010
Start Page
2872
End Page
2878
DOI
10.1364/AO.49.002872

Fiber-optic interferometric two-dimensional scattering-measurement system

We present a fiber-optic interferometric system for measuring depth-resolved scattering in two angular dimensions using Fourier-domain low-coherence interferometry. The system is a unique hybrid of the Michelson and Sagnac interferometer topologies. The collection arm of the interferometer is scanned in two dimensions to detect angular scattering from the sample, which can then be analyzed to determine the structure of the scatterers. A key feature of the system is the full control of polarization of both the illumination and the collection fields, allowing for polarization-sensitive detection, which is essential for twodimensional angular measurements. System performance is demonstrated using a double-layer microsphere phantom. Experimental data from samples with different sizes and acquired with different polarizations show excellent agreement with Mie theory, producing structural measurements with subwavelength accuracy. © 2010 Optical Society of America.

Authors
Zhu, Y; Giacomelli, MG; Wax, A
MLA Citation
Zhu, Y, Giacomelli, MG, and Wax, A. "Fiber-optic interferometric two-dimensional scattering-measurement system." Optics Letters 35.10 (2010): 1641-1643.
Website
http://hdl.handle.net/10161/4231
PMID
20479835
Source
scival
Published In
Optics Letters
Volume
35
Issue
10
Publish Date
2010
Start Page
1641
End Page
1643
DOI
10.1364/OL.35.001641

Measuring morphological features using light-scattering spectroscopy and Fourier-domain low-coherence interferometry

We present measurements of morphological features in a thick turbid sample using light-scattering spectroscopy (LSS) and Fourier-domain low-coherence interferometry (fLCI) by processing with the dual-window (DW) method. A parallel frequency domain optical coherence tomography (OCT) system with a white-light source is used to image a two-layer phantom containing polystyrene beads of diameters 4.00 and 6.98 μm on the top and bottom layers, respectively. The DW method decomposes each OCT A-scan into a time-frequency distribution with simultaneously high spectral and spatial resolution. The spectral information from localized regions in the sample is used to determine scatterer structure. The results show that the two scatterer populations can be differentiated using LSS and fLCI. © 2010 Optical Society of America.

Authors
Robles, FE; Wax, A
MLA Citation
Robles, FE, and Wax, A. "Measuring morphological features using light-scattering spectroscopy and Fourier-domain low-coherence interferometry." Optics Letters 35.3 (2010): 360-362.
Website
http://hdl.handle.net/10161/4226
PMID
20125721
Source
scival
Published In
Optics Letters
Volume
35
Issue
3
Publish Date
2010
Start Page
360
End Page
362
DOI
10.1364/OL.35.000360

Quantitative phase microscopy of live biological cell dynamics

Interferometric phase microscopy of biological cell dynamics has the potential to provide a label-free quantitative tool for cell biology, as well as for medical diagnosis and monitoring. The current state of the art of this field, the open questions, and specific solutions developed in our laboratory will be presented. © 2010 American Institute of Physics.

Authors
Shaked, NT; Wax, A
MLA Citation
Shaked, NT, and Wax, A. "Quantitative phase microscopy of live biological cell dynamics." AIP Conference Proceedings 1236 (2010): 283-288.
Source
scival
Published In
AIP Conference Proceedings
Volume
1236
Publish Date
2010
Start Page
283
End Page
288

Measuring structural features using a dual window method for light scattering spectroscopy and Fourier-domain low coherence interferometry

Light scattering spectroscopy (LSS) and Fourier domain low coherence interferometry (fLCI) are used in combination with the dual window method (DW) to measure scattering features from a thick turbid sample. By processing with the DW method, the trade off that hinders spectroscopic OCT is avoided, thus yielding depth resolved spectra with simultaneously high spatial and spectral resolution. The capabilities of the method are demonstrated by analyzing a double layer phantom, where the top layer contains polystyrene beads of diameter d = 4.00 μm, and the bottom layer contains beads of d = 6.98 μm. A white light parallel frequency domain OCT system is used to image the sample. The results show that scattering structure can be assessed accurately and precisely throughout the whole OCT image using LSS and fLCI. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Authors
Robles, FE; Wax, A
MLA Citation
Robles, FE, and Wax, A. "Measuring structural features using a dual window method for light scattering spectroscopy and Fourier-domain low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7573 (2010).
Source
scival
Published In
Proceedings of SPIE
Volume
7573
Publish Date
2010
DOI
10.1117/12.842375

Fourier-domain angle-resolved low coherence interferometry for clinical detection of dysplasia

Improved methods for detecting dysplasia, or pre-cancerous growth are a current clinical need, particularly in the esophagus. The currently accepted method of random biopsy and histological analysis provides only a limited examination of tissue in question while being coupled with a long time delay for diagnosis. Light scattering spectroscopy, in contrast, allows for inspection of the cellular structure and organization of tissue in vivo. Fourier-domain angle-resolved low-coherence interferometry (a/LCI) is a novel light scattering spectroscopy technique that provides quantitative depth-resolved morphological measurements of the size and optical density of the examined cell nuclei, which are characteristic biomarkers of dysplasia. Previously, clinical viability of the a/LCI system was demonstrated through analysis of ex vivo human esophageal tissue in Barrett's esophagus patients using a portable a/LCI, as was the development of a clinical a/LCI system. Data indicating the feasibility of the technique in other organ sites (colon, oral cavity) will be presented. We present an adaptation of the a/LCI system that will be used to investigate the presence of dysplasia in vivo in Barrett's esophagus patients. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Authors
Terry, NG; Zhu, Y; Wax, A
MLA Citation
Terry, NG, Zhu, Y, and Wax, A. "Fourier-domain angle-resolved low coherence interferometry for clinical detection of dysplasia." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7573 (2010).
Source
scival
Published In
Proceedings of SPIE
Volume
7573
Publish Date
2010
DOI
10.1117/12.842464

Scanning fiber system for angle-resolved low coherence interferometry

We propose a fiber-optic system for Fourier-domain angle-resolved low coherence interferometry. The system is based on singlemode fiber couplers and employs a scanning fiber to collect the angular scattering distribution of the sample. The measured distribution is then fitted to Mie theory to estimate the size of the scatterers. Depth resolution is achieved with Fourier-domain low coherence Mach-Zehnder interferometry. The sample arm of the interferometer illuminates the specimen with polarized light and collects back-scattered light from the sample. The probe's optical performance is evaluated and its depth-resolved sizing capability is demonstrated with subwavelength accuracy using a two-layer microsphere phantom. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Authors
Zhu, Y; Terry, NG; Giacomelli, MG; Wax, A
MLA Citation
Zhu, Y, Terry, NG, Giacomelli, MG, and Wax, A. "Scanning fiber system for angle-resolved low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7573 (2010).
PMID
19838271
Source
scival
Published In
Proceedings of SPIE
Volume
7573
Publish Date
2010
DOI
10.1117/12.842093

Two-wavelength quantitative phase unwrapping of dynamic biological processes

We present two-wavelength phase unwrapping system designs on asynchronous and dynamic phase microscopy techniques developed in our laboratory. The use of two wavelengths in these systems enables quantitative phase imaging without 2π-ambiguities. ©2009 Optical Society of America.

Authors
Rinehart, MT; Shaked, NT; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, and Wax, A. "Two-wavelength quantitative phase unwrapping of dynamic biological processes." 2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009 (November 18, 2009).
Source
scopus
Published In
2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009
Publish Date
2009

Dynamic quantitative phase microscopy of biological cells

We introduce a new fast and accurate method for dynamic quantitative phase imaging of biological cells. The method enables imaging of sub-millisecond dynamic biological phenomena with sub-nanometer temporal stability. Initial experimental results are given. ©2009 Optical Society of America.

Authors
Shaked, NT; Rinehart, MT; Wax, A
MLA Citation
Shaked, NT, Rinehart, MT, and Wax, A. "Dynamic quantitative phase microscopy of biological cells." 2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009 (November 16, 2009).
Source
scopus
Published In
2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009
Publish Date
2009

Rational selection of gold nanorod geometry for label-free plasmonic biosensors.

We present the development of an analytical model that can be used for the rational design of a biosensor based on shifts in the local surface plasmon resonance (LSPR) of individual gold nanoparticles. The model relates the peak wavelength of light scattered by an individual plasmonic nanoparticle to the number of bound analyte molecules and provides an analytical formulation that predicts relevant figures-of-merit of the sensor such as the molecular detection limit (MDL) and dynamic range as a function of nanoparticle geometry and detection system parameters. The model calculates LSPR shifts for individual molecules bound by a nanorod, so that the MDL is defined as the smallest number of bound molecules that is measurable by the system, and the dynamic range is defined as the maximum number of molecules that can be detected by a single nanorod. This model is useful because it will allow a priori design of an LSPR sensor with figures-of-merit that can be optimized for the target analyte. This model was used to design an LSPR sensor based on biotin-functionalized gold nanorods that offers the lowest MDL for this class of sensors. The model predicts a MDL of 18 streptavidin molecules for this sensor, which is in good agreement with experiments and estimates. Further, we discuss how the model can be utilized to guide the development of future generations of LSPR biosensors.

Authors
Nusz, GJ; Curry, AC; Marinakos, SM; Wax, A; Chilkoti, A
MLA Citation
Nusz, GJ, Curry, AC, Marinakos, SM, Wax, A, and Chilkoti, A. "Rational selection of gold nanorod geometry for label-free plasmonic biosensors." ACS Nano 3.4 (April 28, 2009): 795-806.
PMID
19296619
Source
pubmed
Published In
ACS Nano
Volume
3
Issue
4
Publish Date
2009
Start Page
795
End Page
806
DOI
10.1021/nn8006465

Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles.

OBJECTIVE: The goal of this study was to assess whether immunolabeled nanoparticle biomarkers are comparable to fluorescent marker imaging in measuring epidermal growth factor receptor (EGFR) expression. MATERIALS AND METHODS: EGFR expression was quantified using both imaging methods in four cell lines: A431 human epidermoid carcinoma cells, which are known to have high EGFR expression; two cell lines with lower EGFR expression (270-GBM human glioblastoma xenograft cells and H2224 human glioblastoma xenograft cells); and MDA-MB-453 breast carcinoma cells, which do not express EGFR. To enhance contrast of the nanoparticle biomarkers, a darkfield microspectroscopy system was used that includes a custom epi-illumination light train. RESULTS: Nanoparticle-bound cells were clearly distinguished from control cells not bound to nanoparticles in that they showed a significant increase in detected intensity under darkfield illumination due to nanoparticle scattering. The average nanoparticle-scattering intensity for A431 cells was 41.5 counts per cell compared with 24.7 for 270-GBM cells, 8.77 for H2224 cells, and 0.44 for MDA-MB-453 cells. The average fluorescence intensity for A431 cells was 35.3 counts per cell compared with 28.7 for 270-GBM cells, 5.91 for H2224 cells, and 2.07 for MDA-MB-453 cells. A plot of fluorescence intensity versus nanoparticle-scattering intensity for all four cell lines showed that the data agree with a linear relationship given by the following equation: NP = 1.0691 x FL - 0.3873, where NP is the nanoparticle-scattering intensity and FL is the fluorescence intensity. The covariance of the data with the trend line was R(2) = 0.9409. The average peak wavelength of nanoparticle scattering was 570.93 nm for A431 cells, 565.26 nm for 270-GBM cells, and 562.70 nm for H2224 cells (with no clear peaks observed for MDA-MB-453 cells). This spectral trend shows that nanoparticle scattering may reveal additional information about their nanoenvironment via refractive index sensitivity. CONCLUSION: Immunolabeled nanoparticles can quantify receptor expression with performance comparable to fluorescence markers and show promise to better characterize receptor expression via their refractive index sensitivity.

Authors
Crow, MJ; Grant, G; Provenzale, JM; Wax, A
MLA Citation
Crow, MJ, Grant, G, Provenzale, JM, and Wax, A. "Molecular imaging and quantitative measurement of epidermal growth factor receptor expression in live cancer cells using immunolabeled gold nanoparticles." AJR Am J Roentgenol 192.4 (April 2009): 1021-1028.
PMID
19304709
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
192
Issue
4
Publish Date
2009
Start Page
1021
End Page
1028
DOI
10.2214/AJR.07.3535

Nonlinear osmotic properties of the cell nucleus.

In the absence of active volume regulation processes, cell volume is inversely proportional to osmolarity, as predicted by the Boyle Van't Hoff relation. In this study, we tested the hypothesis that nuclear volume has a similar relationship with extracellular osmolarity in articular chondrocytes, cells that are exposed to changes in the osmotic environment in vivo. Furthermore, we explored the mechanism of the relationships between osmolarity and nuclear size and shape. Nuclear size was quantified using two independent techniques, confocal laser scanning microscopy and angle-resolved low coherence interferometry. Nuclear volume was osmotically sensitive but this relationship was not linear, showing a decline in the osmotic sensitivity in the hypo-osmotic range. Nuclear shape was also influenced by extracellular osmolarity, becoming smoother as the osmolarity decreased. The osmotically induced changes in nuclear size paralleled the changes in nuclear shape, suggesting that shape and volume are interdependent. The osmotic sensitivity of shape and volume persisted after disruption of the actin cytoskeleton. Isolated nuclei contracted in response to physiologic changes in macromolecule concentration but not in response to physiologic changes in ion concentration, suggesting solute size has an important influence on the osmotic pressurization of the nucleus. This finding in turn implies that the diffusion barrier that causes osmotic effects is not a semi-permeable membrane, but rather due to size constraints that prevent large solute molecules from entering small spaces in the nucleus. As nuclear morphology has been associated previously with cell phenotype, these findings may provide new insight into the role of mechanical and osmotic signals in regulating cell physiology.

Authors
Finan, JD; Chalut, KJ; Wax, A; Guilak, F
MLA Citation
Finan, JD, Chalut, KJ, Wax, A, and Guilak, F. "Nonlinear osmotic properties of the cell nucleus." Ann Biomed Eng 37.3 (March 2009): 477-491.
PMID
19107599
Source
pubmed
Published In
Annals of Biomedical Engineering
Volume
37
Issue
3
Publish Date
2009
Start Page
477
End Page
491
DOI
10.1007/s10439-008-9618-5

Development of an integrated multiplexed low coherence interferometer and fluorescence clinical endoscope

The performance of a novel clinical endoscope with integrated multiplexed LCI and fluorescence measurements is evaluated. Feasibility and accuracy for measuring microbicidal gel distribution and thickness in the vaginal tract will be assessed. © 2009 Optical Society of America.

Authors
Kim, KH; Drake, TK; DeSoto, MG; Henderson, MH; Katz, DF; Wax, A
MLA Citation
Kim, KH, Drake, TK, DeSoto, MG, Henderson, MH, Katz, DF, and Wax, A. "Development of an integrated multiplexed low coherence interferometer and fluorescence clinical endoscope." Optics InfoBase Conference Papers (January 1, 2009).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2009

Molecular imaging and darkfield microspectroscopy of live cells using gold plasmonic nanoparticles

Noble metal nanoparticles exhibit a plasmonic resonance that provides them with unique optical properties. The sensitivity of the plasmonic resonance to the surrounding dielectric environment has lead to the development of metal nanoparticles as the basis of biosensing schemes. The sharp enhancement in scattering and absorption at the plasmonic resonance frequency has been exploited to develop metal nanoparticles as imaging contrast agents. In this review article, we recap recent efforts that combine both of these features of metal nanoparticles to enable simultaneous molecular imaging and environmental sensing through the use of darkfield microspectroscopy schemes. Recent experimental results demonstrate molecular imaging of epidermal growth factor receptor in live cancer cells and show that additional information can be obtained by monitoring changes in the plasmonic resonance through darkfield microspectroscopy. © 2009 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Wax, A; Sokolov, K
MLA Citation
Wax, A, and Sokolov, K. "Molecular imaging and darkfield microspectroscopy of live cells using gold plasmonic nanoparticles." Laser and Photonics Reviews 3.1-2 (2009): 146-158.
Source
scival
Published In
Laser & Photonics Reviews
Volume
3
Issue
1-2
Publish Date
2009
Start Page
146
End Page
158
DOI
10.1002/lpor.200810011

Multiplexed low coherence interferometry instrument for measuring microbicide gel thickness distribution

We present a Fourier-domain, multiplexed low coherence interferometry (LCI) instrument designed for application to intravaginal measurement of microbicidal gel distribution. Microbicide gels are topical products developed to combat sexually transmitted diseases, such as HIV/AIDS, by acting as delivery vehicles for active drugs and barrier layers to vaginal tissue. Measuring microbicide gel vaginal distribution is key to understanding the gel's biological effectiveness. This study presents a new LCI system for measuring gel distribution that uses six multiplexed channels to achieve broad area scanning without the need for a mechanical scanner. The presented results characterize the performance of the Fourier-domain multiplexed LCI system in measuring gel thickness distribution. The system demonstrates good optical signal-to-noise ratio, steady performance across all channels, negligible cross talk, and accurate measurement with micrometer scale resolution. The potential impact of using a multiplexed LCI system for in vivo measurements is also discussed. © 2008 Optical Society of America.

Authors
Drake, TK; Robles, FE; Wax, A
MLA Citation
Drake, TK, Robles, FE, and Wax, A. "Multiplexed low coherence interferometry instrument for measuring microbicide gel thickness distribution." Applied Optics 48.10 (2009): D14-D19.
PMID
19340102
Source
scival
Published In
Applied Optics
Volume
48
Issue
10
Publish Date
2009
Start Page
D14
End Page
D19
DOI
10.1364/AO.48.000D14

Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis

We present a light scattering study using angle-resolved low coherence interferometry (a/LCI) to assess nuclear morphology and subcellular structure within MCF-7 cells at several time points after treatment with chemotherapeutic agents. Although the nuclear diameter and eccentricity are not observed to change, the light scattering signal reveals a change in the organization of subcellular structures that we interpret using fractal dimension (FD). The FD of subcellular structures in cells treated with paclitaxel and doxorubicin is observed to increase significantly compared with that of control cells as early as 1.5 and 3 hours after application, respectively. The FD is then found to decrease slightly at 6 hours postapplication for both agents only to increase again from 12 to 24 hours posttreatment when the observations ceased. The changes in structure appear over two time scales, suggesting that multiple mechanisms are evident in these early apoptotic stages. Indeed, quantitative image analysis of fluorescence micrographs of cells undergoing apoptosis verifies that the FD of 4′,6-diamidino-2-phenylindole-stained nuclear structures does not change significantly in cells until 12 hours after treatment, whereas that of MitoTracker stained mitochondria is seen to modulate as early as 3 hours after treatment. In contrast, cells receiving an increased dose of paclitaxel that induced G2-M arrest, but not apoptosis, only exhibited the early change in subcellular structure but did not show the later change associated with changes in nuclear substructure. These results suggest that a/LCI may have utility in detecting early apoptotic events for both clinical and basic science applications. ©2009 American Association for Cancer Research.

Authors
Chalut, KJ; Ostrander, JH; Giacomelli, MG; Wax, A
MLA Citation
Chalut, KJ, Ostrander, JH, Giacomelli, MG, and Wax, A. "Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis." Cancer Research 69.3 (2009): 1199-1204.
PMID
19141640
Source
scival
Published In
Cancer Research
Volume
69
Issue
3
Publish Date
2009
Start Page
1199
End Page
1204
DOI
10.1158/0008-5472.CAN-08-3079

Dual-interference-channel quantitative-phase microscopy of live cell dynamics

We introduce and experimentally demonstrate a fast and accurate method for quantitative imaging of the dynamics of live biological cells. Using a dual-channel interferometric setup, two phase-shifted interferograms of nearly transparent biological samples are acquired in a single digital camera exposure and digitally processed into the phase profile of the sample. Since two interferograms of the same sample are acquired simultaneously, most of the common phase noise is eliminated, enabling the visualization of millisecond-scale dynamic biological phenomena with subnanometer optical path length temporal stability. © 2009 Optical Society of America.

Authors
Shaked, NT; Rinehart, MT; Wax, A
MLA Citation
Shaked, NT, Rinehart, MT, and Wax, A. "Dual-interference-channel quantitative-phase microscopy of live cell dynamics." Optics Letters 34.6 (2009): 767-769.
PMID
19282926
Source
scival
Published In
Optics Letters
Volume
34
Issue
6
Publish Date
2009
Start Page
767
End Page
769
DOI
10.1364/OL.34.000767

Experimental verification of T-matrix-based inverse light scattering analysis for assessing structure of spheroids as models of cell nuclei

Inverse light scattering analysis (ILSA) seeks to associate measured scattering properties with the most probable theoretical scattering distribution, making it a useful tool for assessing structure in biological materials. The accuracy of ILSA depends on the compatibility of the light scattering geometry with the light scattering model. In this study, we compare the accuracy obtained when analyzing light scattering data from spheroids using a numerical implementation of Mie theory, and the T matrix, a numerical method of solving light scattering from spheroids. Our experimental data are acquired using novel optical phantoms containing spheroidal scatterers and angle-resolved low-coherence interferometry, a depthand angle-resolved light scattering measurement modality. The results show that Mie theory can accurately assess spheroidal structure despite the geometric incompatibility provided measurements are taken in multiple orientations of the sample relative to the incident polarization and the measured scattering angle. In comparison, analysis using the T-matrix method is highly accurate and more reliable yet requires measurements from only a single orientation. © 2009 Optical Society of America.

Authors
Amoozegar, C; Giacomelli, MG; Keener, JD; Chalut, KJ; Wax, A
MLA Citation
Amoozegar, C, Giacomelli, MG, Keener, JD, Chalut, KJ, and Wax, A. "Experimental verification of T-matrix-based inverse light scattering analysis for assessing structure of spheroids as models of cell nuclei." Applied Optics 48.10 (2009): D20-D25.
PMID
19340110
Source
scival
Published In
Applied Optics
Volume
48
Issue
10
Publish Date
2009
Start Page
D20
End Page
D25
DOI
10.1364/AO.48.000D20

Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution

Current methods for analysis of spectroscopic optical coherence tomography (SOCT) signals suffer from an inherent tradeoff between time (depth) and frequency (wavelength) resolution. Here, we present a dual window (DW) method for reconstructing time frequency distributions (TFDs) that applies two orthogonal Gaussian windows that independently determine the spectral and temporal resolution. The effectiveness of the method is demonstrated in simulations and in processing of measured OCT signals that contain fields which vary in time and frequency. The DW method yields TFDs that maintain high spectral and temporal resolution and are free from the artifacts and limitations commonly observed with other processing methods. © 2009 Optical Society of America.

Authors
Robles, F; Graf, RN; Wax, A
MLA Citation
Robles, F, Graf, RN, and Wax, A. "Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution." Optics Express 17.8 (2009): 6799-6812.
PMID
19365509
Source
scival
Published In
Optics express
Volume
17
Issue
8
Publish Date
2009
Start Page
6799
End Page
6812
DOI
10.1364/OE.17.006799

Simultaneous molecular imaging of EGFR and HER2 using hyperspectral darkfield microscopy and immunotargeted nanoparticles

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER2) contribute to the regulation of cell proliferation, and when jointly over-expressed are associated with several types of cancer. The ability to monitor both receptors simultaneously results in a more accurate indicator of degree of cancerous activity than either receptor alone. Plasmonic nanoparticles (NPs) show promise as a potential EGFR and HER2 biomarker over alternatives such as fluorophores and quantum dots, which are limited by their cytotoxicity and photobleaching. To observe immunolabeled NPs bound to receptor-expressing cells, our past experiments were conducted using a novel optical darkfield microspectroscopy system. We implemented an epi-illumination darkfield broadband light train, which allows for darkfield analysis of live cells in culture with enhanced NP contrast. Under this setup, molecularly specific binding of NPs immunolabeled with anti-EGFR was confirmed. We have since adapted our darkfield setup, which previously only obtained spectral information from a line imaging spectrometer, to incorporate hyperspectral imaging capabilities, allowing widefield data acquisition within seconds. The new system has been validated through observation of shifts in the peak wavelength of scattering by gold NPs on silanated cover glasses using several immersion media. Peak resonant scattering wavelengths match well with that predicted by Mie theory. We will further demonstrate the potential of the system with simultaneous molecular imaging of multiple receptors in vitro using labeled EGFR+/HER2+ SK-BR-3 human breast cancer cells with anti-EGFR immunolabeled gold nanospheres and anti-HER2 immunolabeled gold nanorods, with each scattering in different spectral windows. Additional trials will be performed to demonstrate molecularly specific binding using EGFR+/HER2- MDA-MB-468 and HER2+/EGFR- MDA-MB-453 breast cancer cells. © 2009 SPIE.

Authors
Crow, M; Marinakos, S; Chilkoti, A; Wax, A
MLA Citation
Crow, M, Marinakos, S, Chilkoti, A, and Wax, A. "Simultaneous molecular imaging of EGFR and HER2 using hyperspectral darkfield microscopy and immunotargeted nanoparticles." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7192 (2009).
Source
scival
Published In
Proceedings of SPIE
Volume
7192
Publish Date
2009
DOI
10.1117/12.808968

Nonlinear osmotic properties of the cell nucleus

Authors
Finan, JD; Chalut, KJ; Wax, A; Guilak, F
MLA Citation
Finan, JD, Chalut, KJ, Wax, A, and Guilak, F. "Nonlinear osmotic properties of the cell nucleus." Proceedings of the ASME Summer Bioengineering Conference 2009, SBC2009 PART A (2009): 93-94.
Source
scival
Published In
Proceedings of the ASME Summer Bioengineering Conference 2009, SBC2009
Issue
PART A
Publish Date
2009
Start Page
93
End Page
94
DOI
10.1115/SBC2009-206197

Development of an integrated endoscopic device for multiplexed low coherence interferometry (LCI) measurements of microbicide gel thickness

Microbicide gels are topical products that have recently been developed to combat sexually transmitted diseases including HIV/AIDS. The extent of gel coverage, thickness, and structure are crucial factors in gel effectiveness. It is necessary to be able to monitor gel distribution and behavior under various circumstances, such as coatis, and over an extended time scale in vivo. We have developed a multiplexed, Fourier-domain low coherence interferometry (LCI) system as a practical method of measuring microbicide gel distribution, with precision and accuracy comparable to currently used fluorometric techniques. The multiplexed system achieved a broad scanning area without the need for a mechanical scanning device, typical of OCT systems, by utilizing six parallel channels with simultaneous data collection. We now propose an imaging module, which will allow the integration of the multiplexed LCI system into the current fluorescence system in conjunction with an endoscope. The LCI imaging module will meet several key criteria in order to be compatible with the current system. The fluorescent system features a 4-mm diameter rigid endoscope enclosed in a 19-mm diameter polycarbonate tube, with a water immersion tip. Therefore, the LCI module must be low profile as well as water-resistant to fit inside the current design. It also must fulfill its primary function of delivering light from each of the six channels to the gel and collecting backscattered light. The performance of the imaging module will be characterized by scanning a calibration socket which contains grooves of known depths, and comparing these measurements to the fluorimetric results. © 2009 SPIE.

Authors
Drake, TK; Robles, F; DeSoto, M; Henderson, MH; Katz, DF; Wax, A
MLA Citation
Drake, TK, Robles, F, DeSoto, M, Henderson, MH, Katz, DF, and Wax, A. "Development of an integrated endoscopic device for multiplexed low coherence interferometry (LCI) measurements of microbicide gel thickness." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7169 (2009).
Source
scival
Published In
Proceedings of SPIE
Volume
7169
Publish Date
2009
DOI
10.1117/12.809114

Scanning fiber angle-resolved low coherence interferometry

We present a fiber-optic probe for Fourier-domain angle-resolved low coherence interferometry for the determination of depth-resolved scatterer size. The probe employs a scanning single-mode fiber to collect the angular scattering distribution of the sample, which is analyzed using the Mie theory to obtain the average size of the scatterers. Depth sectioning is achieved with low coherence Mach-Zehnder interferometry. In the sample arm of the interferometer, a fixed fiber illuminates the sample through an imaging lens and a collection fiber samples the backscattered angular distribution by scanning across the Fourier plane image of the sample. We characterize the optical performance of the probe and demonstrate the ability to execute depth-resolved sizing with subwavelength accuracy by using a double-layer phantom containing two sizes of polystyrene microspheres. © 2009 Optical Society of America.

Authors
Zhu, Y; Terry, NG; Wax, A
MLA Citation
Zhu, Y, Terry, NG, and Wax, A. "Scanning fiber angle-resolved low coherence interferometry." Optics Letters 34.20 (2009): 3196-3198.
Source
scival
Published In
Optics Letters
Volume
34
Issue
20
Publish Date
2009
Start Page
3196
End Page
3198
DOI
10.1364/OL.34.003196

Two-step-only phase-shifting interferometry with optimized detector bandwidth for microscopy of live cells

We present a phase-shifting interferometric technique for imaging live biological cells in growth media, while optimizing spatial resolution and enabling potential real-time measurement capabilities. The technique uses slightly-off-axis interferometry which requires less detector bandwidth than traditional off-axis interferometry and fewer measurements than traditional on-axis interferometry. Experimental and theoretical comparisons between the proposed method and these traditional interferometric approaches are given. The method is experimentally demonstrated via phase microcopy of live human skin cancer cells. © 2009 Optical Society of America.

Authors
Shaked, NT; Zhu, Y; Rinehart, MT; Wax, A
MLA Citation
Shaked, NT, Zhu, Y, Rinehart, MT, and Wax, A. "Two-step-only phase-shifting interferometry with optimized detector bandwidth for microscopy of live cells." Optics Express 17.18 (2009): 15585-15591.
PMID
19724557
Source
scival
Published In
Optics express
Volume
17
Issue
18
Publish Date
2009
Start Page
15585
End Page
15591
DOI
10.1364/OE.17.015585

Reflectance Spectroscopy

Reflectance spectroscopy is an emerging technology which provides rapid and safe evaluation of tissue for dysplasia and ischemia. The probe-based devices can be passed through most endoscopes. Current applications include detection of dysplasia in Barrett's esophagus, colitis, and colon polyps. © 2009.

Authors
Wallace, MB; Wax, A; Roberts, DN; Graf, RN
MLA Citation
Wallace, MB, Wax, A, Roberts, DN, and Graf, RN. "Reflectance Spectroscopy." Gastrointestinal Endoscopy Clinics of North America 19.2 (2009): 233-242.
PMID
19423021
Source
scival
Published In
Gastrointestinal Endoscopy Clinics of North America
Volume
19
Issue
2
Publish Date
2009
Start Page
233
End Page
242
DOI
10.1016/j.giec.2009.02.008

Dynamic quantitative phase microscopy of biological cells

We introduce a new fast and accurate method for dynamic quantitative phase imaging of biological cells. The method enables imaging of sub-millisecond dynamic biological phenomena with sub-nanometer temporal stability. Initial experimental results are given. ©2009 Optical Society of America.

Authors
Shaked, NT; Rinehart, MT; Wax, A
MLA Citation
Shaked, NT, Rinehart, MT, and Wax, A. "Dynamic quantitative phase microscopy of biological cells." 2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009 (2009).
Source
scival
Published In
2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009
Publish Date
2009

Detecting precancerous lesions in the hamster cheek pouch using spectroscopic white-light optical coherence tomography to assess nuclear morphology via spectral oscillations

We have developed a novel dual-window approach for spectroscopic optical coherence tomography (OCT) measurements and applied it to probe nuclear morphology in tissue samples drawn from the hamster cheek pouch carcinogenesis model. The dualwindow approach enables high spectral and depth resolution simultaneously, allowing detection of spectral oscillations, which we isolate to determine the structure of cell nuclei in the basal layer of the epithelium. The measurements were executed with our parallel frequency domain OCT system, which uses light from a thermal source, providing high bandwidth and access to the visible portion of the spectrum. The structural measurements show a highly statistically significant difference between untreated (normal) and treated (hyperplastic/dysplastic) tissues, indicating the potential utility of this approach as a diagnostic method. © 2009 Society of Photo-Optical Instrumentation Engineers.

Authors
Graf, RN; Robles, FE; Chen, X; Wax, A
MLA Citation
Graf, RN, Robles, FE, Chen, X, and Wax, A. "Detecting precancerous lesions in the hamster cheek pouch using spectroscopic white-light optical coherence tomography to assess nuclear morphology via spectral oscillations." Journal of Biomedical Optics 14.6 (2009).
PMID
20059268
Source
scival
Published In
Journal of Biomedical Optics
Volume
14
Issue
6
Publish Date
2009
DOI
10.1117/1.3269680

Two-wavelength quantitative phase unwrapping of dynamic biological processes

We present two-wavelength phase unwrapping system designs on asynchronous and dynamic phase microscopy techniques developed in our laboratory. The use of two wavelengths in these systems enables quantitative phase imaging without 2π-ambiguities. ©2009 Optical Society of America.

Authors
Rinehart, MT; Shaked, NT; Wax, A
MLA Citation
Rinehart, MT, Shaked, NT, and Wax, A. "Two-wavelength quantitative phase unwrapping of dynamic biological processes." 2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009 (2009).
Source
scival
Published In
2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum Electronics and Laser Science Conference, CLEO/QELS 2009
Publish Date
2009

Optimizing Fourier-domain angle resolved low coherence interferometry for clinical use

Methods for the optimization of a/LCI for clinical use are presented. First, the use of the T-matrix light scattering model to simulate scattering from spheroidal particles is presented as a more appropriate simulation of cell nuclei scattering than the previously used Mie theory. In addition, the use of a broadband light source with a bandwidth greater than 50nm similar to those utilized in OCT applications is demonstrated. Accurate sizing of scatterers in tissue phantoms containing stretched and unstretched polystyrene microspheres along with measurements of unstretched polystyrene microspheres in solution are presented, demonstrating advances in system performance and design. In addition, preliminary human in vivo esophageal tissue data are presented. © 2009 SPIE.

Authors
Terry, NG; Zhu, Y; Rinehart, M; Wax, A
MLA Citation
Terry, NG, Zhu, Y, Rinehart, M, and Wax, A. "Optimizing Fourier-domain angle resolved low coherence interferometry for clinical use." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7187 (2009).
Source
scival
Published In
Proceedings of SPIE
Volume
7187
Publish Date
2009
DOI
10.1117/12.808021

Detecting neoplastic development in the hamster cheek pouch using Fourier Domain Low Coherence Interferometry

Fourier Domain Low Coherence Interferometry (fLCI) is an optical technique that recovers depth-resolved spectroscopic information about scatterers. The current fLCI system utilizes a white light Xe arc lamp source, a 4-f interferometer, and an imaging spectrometer at the detection plane to acquire spectra from 256 adjacent spatial points. This configuration permits the acquisition of ultrahigh depth resolution Fourier domain OCT images without the need for any beam scanning. fLCI has traditionally obtained depth-resolved spectral information by performing a short-time Fourier transform (STFT) on the detected spectra, similar to the processing techniques of spectroscopic OCT. We now employ a dual Gaussian window processing method which simultaneously obtains high spectral and temporal resolution, thus avoiding the resolution trade-off normally associated with the STFT. Wavelength dependent variations in scattering intensity are analyzed as a function of depth to obtain structural information about the probed scatterers. We now verify fLCI's ability to distinguish between normal and dysplastic epithelial tissue using the hamster cheek pouch model. Thirty hamsters will have one cheek pouch treated with the known carcinogen DMBA. At the conclusion of the 24 week treatment period the animals will be anesthetized and the cheek pouches will be extracted. We will use the fLCI optical system to measure the neoplastic transformation of the in situ subsurface tissue layers in both the normal and DMBA-treated cheek pouches. Traditional histological analysis will be used to verify the fLCI measurements. Our results will further establish fLCI as an effective method for distinguishing between normal and dysplastic epithelial tissues. © 2009 SPIE.

Authors
Graf, RN; Robles, F; Chen, X; Wax, A
MLA Citation
Graf, RN, Robles, F, Chen, X, and Wax, A. "Detecting neoplastic development in the hamster cheek pouch using Fourier Domain Low Coherence Interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7187 (2009).
Source
scival
Published In
Proceedings of SPIE
Volume
7187
Publish Date
2009
DOI
10.1117/12.809494

T-matrix based inverse light scattering analysis using angle resolved low coherence interferometry

Inverse light scattering methods have been applied by several groups as a means to probe cellular structure in both clinical and scientific applications with sub-wavelength accuracy. These methods determine the geometric properties of tissue scatterers based on far field scattering patterns. Generally, structure is determined by measuring scattering over some range of angles, wavelengths, or polarizations and then fitting the observed data to a database of simulated scattering selected from a range of probable geometries. We have developed new light scattering software based on the T-matrix method that creates databases of scattering from spheroidal objects, representing a substantial improvement over Mie theory, a method limited to simulating scattering from spheres. The computational cost of the T-matrix method is addressed through a simple but massively parallel program that concurrently simulates scattering across hundreds of PCs. We are exploring the use of these T-matrix databases in inverting interferometric measurements of angle-resolved scattering from spheroidal cell nuclei using a technique called angle-resolved low coherence interferometry (a/LCI). With a/LCI, we have previously distinguished between healthy and dysplastic tissue in both cell cultures and in ex vivo rat and hamster tissue using Mie theory to measure nuclear diameter. We now present nuclear volume and spheroidal aspect ratio measurements of unstained, living MCF7 cells using the improved T-matrix database to analyze a/LCI data. We achieve measurement accuracy equivalent to conventional image analysis of stained samples. We will further validate the approach by comparing experimental measurements of scattering from polystyrene microspheroids, and show that the T-matrix is a suitable replacement for Mie theory in ex vivo tissue samples. © 2009 PIE.

Authors
Giacomelli, M; Chalut, K; Ostrander, J; Wax, A
MLA Citation
Giacomelli, M, Chalut, K, Ostrander, J, and Wax, A. "T-matrix based inverse light scattering analysis using angle resolved low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7187 (2009).
Source
scival
Published In
Proceedings of SPIE
Volume
7187
Publish Date
2009
DOI
10.1117/12.808059

Dual window method for processing spectroscopic optical coherence tomography signals with high spectral and spatial resolution

The generation of spectroscopic optical coherence tomography (SOCT) signals suffers from an inherent trade off between spatial and spectral resolution. Here, we present a dual window (DW) method that uses two Gaussian windows to simultaneously obtain high spectral and spatial resolution. We show that the DW method probes the Winger time-frequency distribution (TFD) with two orthogonal windows set by the standard deviation of the Gaussian windows used for processing. We also show that in the limit of an infinitesimally narrow window, combined with a large window, this method is equivalent to the Kirkwood & Richaczek TFD and, if the real part is taken, it is equivalent to the Margenau & Hill (MH) TFD. We demonstrate the effectiveness of the method by simulating a signal with four components separated in depth or center frequency. Six TFD are compared: the ideal, the Wigner, the MH, narrow window short time Fourier transform (STFT), wide window STFT, and the DW. The results show that the DW method contains features of the Wigner TFD, and that it contains the highest spatial and spectral resolution that is free of artifacts. This method can enable powerful applications, including accurate acquisition of the spectral information for cancer diagnosis. © 2009 SPIE.

Authors
Robles, FE; Graf, RN; Wax, A
MLA Citation
Robles, FE, Graf, RN, and Wax, A. "Dual window method for processing spectroscopic optical coherence tomography signals with high spectral and spatial resolution." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 7168 (2009).
Source
scival
Published In
Proceedings of SPIE
Volume
7168
Publish Date
2009
DOI
10.1117/12.809465

Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres.

Molecular imaging is a powerful tool for investigating disease processes and potential therapies in both in vivo and in vitro systems. However, high resolution molecular imaging has been limited to relatively shallow penetration depths that can be accessed with microscopy. Optical coherence tomography (OCT) is an optical analogue to ultrasound with relatively good penetration depth (1-2 mm) and resolution (approximately 1-10 microm). We have developed and characterized photothermal OCT as a molecular contrast mechanism that allows for high resolution molecular imaging at deeper penetration depths than microscopy. Our photothermal system consists of an amplitude-modulated heating beam that spatially overlaps with the focused spot of the sample arm of a spectral-domain OCT microscope. Validation experiments in tissuelike phantoms containing gold nanospheres that absorb at 532 nm revealed a sensitivity of 14 ppm nanospheres (weight/weight) in a tissuelike environment. The nanospheres were then conjugated to anti-EGFR, and molecular targeting was confirmed in cells that overexpress EGFR (MDA-MB-468) and cells that express low levels of EGFR (MDA-MB-435). Molecular imaging in three-dimensional tissue constructs was confirmed with a significantly lower photothermal signal (p<0.0001) from the constructs composed of cells that express low levels of EGFR compared to the overexpressing cell constructs (300% signal increase). This technique could potentially augment confocal and multiphoton microscopy as a method for deep-tissue, depth-resolved molecular imaging with relatively high resolution and target sensitivity, without photobleaching or cytotoxicity.

Authors
Skala, MC; Crow, MJ; Wax, A; Izatt, JA
MLA Citation
Skala, MC, Crow, MJ, Wax, A, and Izatt, JA. "Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres." Nano Lett 8.10 (October 2008): 3461-3467.
PMID
18767886
Source
pubmed
Published In
Nano Letters
Volume
8
Issue
10
Publish Date
2008
Start Page
3461
End Page
3467
DOI
10.1021/nl802351p

Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry.

Accurate measurements of nuclear deformation, i.e., structural changes of the nucleus in response to environmental stimuli, are important for signal transduction studies. Traditionally, these measurements require labeling and imaging, and then nuclear measurement using image analysis. This approach is time-consuming, invasive, and unavoidably perturbs cellular systems. Light scattering, an emerging biophotonics technique for probing physical characteristics of living systems, offers a promising alternative. Angle-resolved low-coherence interferometry (a/LCI), a novel light scattering technique, was developed to quantify nuclear morphology for early cancer detection. In this study, a/LCI is used for the first time to noninvasively measure small changes in nuclear morphology in response to environmental stimuli. With this new application, we broaden the potential uses of a/LCI by demonstrating high-throughput measurements and by probing aspherical nuclei. To demonstrate the versatility of this approach, two distinct models relevant to current investigations in cell and tissue engineering research are used. Structural changes in cell nuclei due to subtle environmental stimuli, including substrate topography and osmotic pressure, are profiled rapidly without disrupting the cells or introducing artifacts associated with traditional measurements. Accuracy > or = 3% is obtained for the range of nuclear geometries examined here, with the greatest deviations occurring for the more complex geometries. Given the high-throughput nature of the measurements, this deviation may be acceptable for many biological applications that seek to establish connections between morphology and function.

Authors
Chalut, KJ; Chen, S; Finan, JD; Giacomelli, MG; Guilak, F; Leong, KW; Wax, A
MLA Citation
Chalut, KJ, Chen, S, Finan, JD, Giacomelli, MG, Guilak, F, Leong, KW, and Wax, A. "Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry." Biophys J 94.12 (June 2008): 4948-4956.
PMID
18326642
Source
pubmed
Published In
Biophysical Journal
Volume
94
Issue
12
Publish Date
2008
Start Page
4948
End Page
4956
DOI
10.1529/biophysj.107.124107

Label-free plasmonic detection of biomolecular binding by a single gold nanorod.

We report the use of individual gold nanorods as plasmonic transducers to detect the binding of streptavidin to individual biotin-conjugated nanorods in real time on a surface. Label-free detection at the single-nanorod level was performed by tracking the wavelength shift of the nanorod-localized surface plasmon resonant scattering spectrum using a dark-field microspectroscopy system. The lowest streptavidin concentration that was experimentally measured was 1 nM, which is a factor of 1000-fold lower than the previously reported detection limit for streptavidin binding by biotinylated single plasmonic nanostructures. We believe that the current optical setup is able to reliably measure wavelength shifts as small as 0.3 nm. Binding of streptavidin at 1 nM concentration induces a mean resonant wavelength shift of 0.59 nm suggesting that we are currently operating at close to the limit of detection of the system.

Authors
Nusz, GJ; Marinakos, SM; Curry, AC; Dahlin, A; Höök, F; Wax, A; Chilkoti, A
MLA Citation
Nusz, GJ, Marinakos, SM, Curry, AC, Dahlin, A, Höök, F, Wax, A, and Chilkoti, A. "Label-free plasmonic detection of biomolecular binding by a single gold nanorod." Anal Chem 80.4 (February 15, 2008): 984-989.
PMID
18197636
Source
pubmed
Published In
Analytical Chemistry
Volume
80
Issue
4
Publish Date
2008
Start Page
984
End Page
989
DOI
10.1021/ac7017348

Analyzing light scattering from aspherical nuclei for cell biology and clinical applications

We discuss new models of light scattering by aspherical cell nuclei and relate them to studies of cell mechanics and early cancer detection based on angle-resolve low coherence interferometry, an inverse light scattering method. © 2008 Optical Society of America.

Authors
Wax, A
MLA Citation
Wax, A. "Analyzing light scattering from aspherical nuclei for cell biology and clinical applications." Optics InfoBase Conference Papers (January 1, 2008).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2008

Quantitative phase microscopy with multi-wavelength unwrapping and tomographic 3D reconstruction

Asynchronous digital holography has been developed for quantitative phase measurements, and will be extended to multi-wavelength phase unwrapping and 3D tomographic reconstruction. Results acquired from standard samples and also live cell samples will be presented. © 2007 Optical Society of America.

Authors
Rinehart, M; Giacomelli, M; Chalut, K; Wax, A
MLA Citation
Rinehart, M, Giacomelli, M, Chalut, K, and Wax, A. "Quantitative phase microscopy with multi-wavelength unwrapping and tomographic 3D reconstruction." Optics InfoBase Conference Papers (January 1, 2008).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2008

Quantitative phase microscopy with multi-wavelength unwrapping and tomographic 3D reconstruction

Asynchronous digital holography has been developed for quantitative phase measurements, and will be extended to multi-wavelength phase unwrapping and 3D tomographic reconstruction. Results acquired from standard samples and also live cell samples will be presented. © 2007 Optical Society of America.

Authors
Rinehart, M; Giacomelli, M; Chalut, K; Wax, A
MLA Citation
Rinehart, M, Giacomelli, M, Chalut, K, and Wax, A. "Quantitative phase microscopy with multi-wavelength unwrapping and tomographic 3D reconstruction." Optics InfoBase Conference Papers (January 1, 2008).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2008

Application of the T-matrix method to determine the structure of spheroidal cell nuclei with angle-resolved light scattering

We demonstrate an inverse light-scattering analysis procedure based on using the T-matrix method as a light-scattering model. We measure light scattered by in vitro cell monolayers using angle-resolved lowcoherence interferometry (a/LCI) and compare the data to predictions of the T-matrix theory. The comparison yields measurements of the equal volume diameter and aspect ratio of the spheroid cell nuclei with accuracy comparable to quantitative image analysis of fixed and stained samples. These improvements represent a significant upgrade for the a/LCI technique, expanding both the range of tissue in which it is applicable and potentially increasing its value as a diagnostic tool. © 2008 Optical Society of America.

Authors
Giacomelli, MG; Chalut, KJ; Ostrander, JH; Wax, A
MLA Citation
Giacomelli, MG, Chalut, KJ, Ostrander, JH, and Wax, A. "Application of the T-matrix method to determine the structure of spheroidal cell nuclei with angle-resolved light scattering." Optics Letters 33.21 (2008): 2452-2454.
PMID
18978884
Source
scival
Published In
Optics Letters
Volume
33
Issue
21
Publish Date
2008
Start Page
2452
End Page
2454
DOI
10.1364/OL.33.002452

Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles

We present a study using plasmonic nanoparticles (NPs) to image epidermal growth factor receptor (EGFR) in live cells. Through detailed analysis of the NP scattering spectra, we determine the intracellular refractive index (RI) within attoliter volumes inside of the living cells. Molecular imaging is demonstrated using anti-EGFR labeled gold nanospheres delivered to cancer cells that overexpress EGFR, with targeted binding confirmed by appropriate control experiments. RI determination is achieved by measurement of the bound NPs' scattering spectra, acquired using a precision dark-field microspectroscopy system and through careful characterization of the NP properties throughout the immuno-labeling procedure. To demonstrate the effect of receptor-mediated uptake, the data are compared to similar spectral measurements using antibody-free NPs, taken up by the cells through nonspecific mechanisms. In these experiments, NP aggregation introduces interparticle effects in the scattering spectra, suggesting that EGFR-mediated internalization of NPs may provide an advantage for maintaining NP isolation upon uptake. The results of this study show the potential utility of dark-field microspectroscopy and labeled NPs for live cell imaging. By demonstrating RI sensitivity over nanometer length scales, this study also presents a potential new avenue for assessing the structure and dynamics of live cells. © 2008 Society of Photo-Optical Instrumentation Engineers.

Authors
Curry, AC; Crow, M; Wax, A
MLA Citation
Curry, AC, Crow, M, and Wax, A. "Molecular imaging of epidermal growth factor receptor in live cells with refractive index sensitivity using dark-field microspectroscopy and immunotargeted nanoparticles." Journal of Biomedical Optics 13.1 (2008).
PMID
18315380
Source
scival
Published In
Journal of Biomedical Optics
Volume
13
Issue
1
Publish Date
2008
DOI
10.1117/1.2837450

In situ nuclear morphology measurements using light scattering as biomarkers of neoplastic change in animal models of carcinogenesis

Light scattering spectroscopy measurements can be used to determine the structure of tissue samples. Through refined data acquisition and signal processing techniques, quantitative nuclear morphology measurements may be obtained from light scattering data. These data have been used primarily as a biomarker of neoplastic change in a wide range of settings. Here, we review the application of light scattering to assessing the health status of tissues drawn from animal models of carcinogenesis, in particular, the rat esophagus and the golden Syrian hamster trachea carcinogenesis models. In addition, we present results from ex vivo human tissues to demonstrate the relevance of the use of animal models which are excellent surrogates for several human cancers. These models provide the opportunity to develop biomarkers and test chemopreventive and therapy strategies before application in humans. © 2008 - IOS Press and the authors. All rights reserved.

Authors
Wax, A; Pyhtila, JW
MLA Citation
Wax, A, and Pyhtila, JW. "In situ nuclear morphology measurements using light scattering as biomarkers of neoplastic change in animal models of carcinogenesis." Disease Markers 25.6 (2008): 291-301.
PMID
19208947
Source
scival
Published In
Disease markers
Volume
25
Issue
6
Publish Date
2008
Start Page
291
End Page
301
DOI
10.1155/2008/584101

Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium

The combination of low-coherence interferometry with angle-resolved light scattering measurements has been shown to be a powerful method for determining the structure of cell nuclei within intact tissue samples. The nuclear morphology data have been used as a biomarker of neoplastic change in a wide range of settings. Here, we review the development of angle-resolved lowcoherence interferometry (a/LCI) for assessing the health status of human esophageal epithelial tissues based on depth-resolved measurements of the morphology of cell nuclei. The design and implementation of clinical instrumentation are reviewed, and results from ex vivo human tissue measurements are presented to validate the capabilities of the technique. In addition to the review of earlier papers, new results are presented, which demonstrate the first application of a portable a/LCI system with a flexible endoscopic probe to assessing depth-resolved nuclear morphology in a clinical setting. High sensitivity for the detection of precancerous tissues is demonstrated. © 2008 IEEE.

Authors
Brown, WJ; Pyhtila, JW; Terry, NG; Chalut, KJ; D'Amico, TA; Sporn, TA; Obando, JV; Wax, A
MLA Citation
Brown, WJ, Pyhtila, JW, Terry, NG, Chalut, KJ, D'Amico, TA, Sporn, TA, Obando, JV, and Wax, A. "Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium." IEEE Journal on Selected Topics in Quantum Electronics 14.1 (2008): 88-96.
Source
scival
Published In
IEEE Journal of Selected Topics in Quantum Electronics
Volume
14
Issue
1
Publish Date
2008
Start Page
88
End Page
96
DOI
10.1109/JSTQE.2007.913969

Application of Mie theory to assess structure of spheroidal scattering in backscattering geometries

Inverse light scattering analysis seeks to associate measured scattering properties with the most probable theoretical scattering distribution. Although Mie theory is a spherical scattering model, it has been used successfully for discerning the geometry of spheroidal scatterers. The goal of this study was an in-depth evaluation of the consequences of analyzing the structure of spheroidal geometries, which are relevant to cell and tissue studies in biology, by employing Mie-theory-based inverse light scattering analysis. As a basis for this study, the scattering from spheroidal geometries was modeled using T-matrix theory and used as test data. In a previous study, we used this technique to investigate the case of spheroidal scatterers aligned with the optical axis. In the present study, we look at a broader scope which includes the effects of aspect ratio, orientation, refractive index, and incident light polarization. Over this wide range of parameters, our results indicate that this method provides a good estimate of spheroidal structure. © 2008 Optical Society of America.

Authors
Chalut, KJ; Giacomelli, MG; Wax, A
MLA Citation
Chalut, KJ, Giacomelli, MG, and Wax, A. "Application of Mie theory to assess structure of spheroidal scattering in backscattering geometries." Journal of the Optical Society of America A: Optics and Image Science, and Vision 25.8 (2008): 1866-1874.
PMID
18677348
Source
scival
Published In
Journal of the Optical Society of America A
Volume
25
Issue
8
Publish Date
2008
Start Page
1866
End Page
1874

Parallel frequency-domain optical coherence tomography scatter-mode imaging of the hamster cheek pouch using a thermal light source

We use a parallel frequency-domain optical coherence tomography (FDOCT) system to generate a scattermode image of the hamster cheek pouch epithelium. To our knowledge, this is the first optical coherence tomography (OCT) image of a biological sample obtained using a thermal light source in the frequency domain. The system employs an imaging spectrometer to acquire depth-resolved profiles from adjacent spatial points without the need for any scanning. To enable this imaging modality, we have considered that signals originating from multiple depths combine in a different manner in FDOCT compared to time-domain optical coherence tomography (TDOCT). Because a multicomponent FDOCT signal is a coherent sum, it is necessary to limit the number of modes that contribute to the detected signal. Conversely, multicomponent TDOCT signals can be represented as incoherent sums, where increasing the number of modes improves the signal. © 2008 Optical Society of America.

Authors
Graf, RN; Brown, WJ; Wax, A
MLA Citation
Graf, RN, Brown, WJ, and Wax, A. "Parallel frequency-domain optical coherence tomography scatter-mode imaging of the hamster cheek pouch using a thermal light source." Optics Letters 33.12 (2008): 1285-1287.
PMID
18552933
Source
scival
Published In
Optics Letters
Volume
33
Issue
12
Publish Date
2008
Start Page
1285
End Page
1287
DOI
10.1364/OL.33.001285

Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres

Molecular imaging is a powerful tool for investigating disease processes and potential therapies in both in vivo and in vitro systems. However, high resolution molecular imaging has been limited to relatively shallow penetration depths that can be accessed with microscopy. Optical coherence tomography (OCT) is an optical analogue to ultrasound with relatively good penetration depth (1-2 mm) and resolution (∼1-10 μm). We have developed and characterized photothermal OCT as a molecular contrast mechanism that allows for high resolution molecular imaging at deeper penetration depths than microscopy. Our photothermal system consists of an amplitude-modulated heating beam that spatially overlaps with the focused spot of the sample arm of a spectral-domain OCT microscope. Validation experiments in tissuelike phantoms containing gold nanospheres that absorb at 532 nm revealed a sensitivity of 14 ppm nanospheres (weight/weight) in a tissuelike environment. The nanospheres were then conjugated to anti-EGFR, and molecular targeting was confirmed in cells that overexpress EGFR (MDA-MB-468) and cells that express low levels of EGFR (MDA-MB-435). Molecular imaging in three-dimensional tissue constructs was confirmed with a significantly lower photothermal signal (p < 0.0001) from the constructs composed of cells that express low levels of EGFR compared to the overexpressing cell constructs (300% signal increase). This technique could potentially augment confocal and multiphoton microscopy as a method for deep-tissue, depth-resolved molecular imaging with relatively high resolution and target sensitivity, without photobleaching or cytotoxicity. © 2008 American Chemical Society.

Authors
Skala, MC; Crow, MJ; Wax, A; Izatt, JA
MLA Citation
Skala, MC, Crow, MJ, Wax, A, and Izatt, JA. "Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres." Nano Letters 8.10 (2008): 3461-3467.
Source
scival
Published In
Nano Letters
Volume
8
Issue
10
Publish Date
2008
Start Page
3461
End Page
3467
DOI
10.1021/nl802351p

Detection of structural and functional changes in biological materials using angle-resolved low coherence interferometry

A well-established method of assessing structure is inverse light scattering analysis. With inverse light scattering analysis, the measured scattering properties of a scatterer(s) are associated with the most probable scattering distribution predicted by an appropriate light scattering model. One commonly used light scattering model is Mie theory, the electromagnetic theory of spherical scattering. Although Mie theory is a spherical scattering model, it has been used for deducing the geometry of spheroidal scatterers, which are important for studies of biological cell structure. The angle-resolved low coherence interferometry (a/LCI) technique is one method of Mie theory - based inverse light scattering analysis that has been used to evaluate biological structure both ex vivo and in vitro. In the present study, we examine the ability of a/LCI to assess structure, geometry, and cellular organization in ways that will further enable the study of function in biological materials.

Authors
Chalut, KJ; Ostrander, JH; Wax, A
MLA Citation
Chalut, KJ, Ostrander, JH, and Wax, A. "Detection of structural and functional changes in biological materials using angle-resolved low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6864 (2008).
Source
scival
Published In
Proceedings of SPIE
Volume
6864
Publish Date
2008
DOI
10.1117/12.764213

Measuring neoplastic transformation in the hamster cheek pouch using Fourier domain low coherence interferometry

Fourier Domain Low Coherence Interferometry (fLCI) is a promising technique which combines the depth resolution of low coherence interferometry with the sensitivity of light scattering spectroscopy for probing the health of epithelial tissue layers. Our new fLCI system configuration utilizes a white light Xe arc lamp source and a 4-f interferometer which re-images light scattered from the sample onto the detection plane. The system employs an imaging spectrometer at the detection plane to acquire depth resolved profiles from 252 adjacent spatial points without the need for any scanning. The limited spatial coherence of the light source requires the resolution of adjacent spatial points for the generation of depth information. Depth-resolved spectral information is recovered by performing a short-time Fourier transform on the detected spectra, similar to spectroscopic optical coherence tomography. Wavelength dependent variations in scattering intensity are analyzed as a function of depth to obtain information about the neoplastic transformation of the probed cells. Previous studies have demonstrated fLCI as an excellent technique for probing the scatterer morphology of simple phantoms and of in vitro cancer cell monolayers. We now seek to assess the ability of the new fLCI system to measure the health of subsurface tissue layers using the hamster cheek pouch model. Seven hamsters will have one cheek pouch treated with the known carcinogen DMBA. At the conclusion of the 24 week treatment period the animals will be anesthetized and the cheek pouches will be extracted. We will use the fLCI optical system to measure the neoplastic transformation of the in situ subsurface tissue layers in both the normal and DMBA-treated cheek pouches. Traditional histological analysis will be used to verify the fLCI measurements. We expect our results to establish the feasibility of fLCI to distinguish between healthy and dysplastic epithelial tissues in the hamster cheek pouch.

Authors
Graf, RN; Chen, X; Brown, W; Wax, A
MLA Citation
Graf, RN, Chen, X, Brown, W, and Wax, A. "Measuring neoplastic transformation in the hamster cheek pouch using Fourier domain low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6864 (2008).
Source
scival
Published In
Proceedings of SPIE
Volume
6864
Publish Date
2008
DOI
10.1117/12.764045

Development of a clinical Fourier-domain angle resolved low coherence interferometry system for in vivo measurements

Improved methods for detecting dysplasia, or pre-cancerous growth are a current clinical need, particularly in the esophagus. The currently accepted method of random biopsy and histological analysis provides only a limited examination of tissue in question while being coupled with a long time delay for diagnosis. Optical scattering spectroscopy, in contrast, allows for inspection of the cellular structure and organization of tissue in vivo. Fourier-domain angle-resolved low-coherence interferometry (a/LCI) is a novel scattering spectroscopy technique that provides quantitative depth-resolved morphological measurements of the size and optical density of the examined cell nuclei, which are characteristic biomarkers of dysplasia. Previously, the clinical viability of the a/LCI system was demonstrated by analysis of ex vivo human esophageal tissue in Barrett's esophagus patients using a portable a/LCI system. We present an adaptation of the portable a/LCI instrument that can be used in the accessory channel of a gastroscope, allowing for in vivo measurements to be taken. Modifications to the previous generation system include the use of an improved imaging spectrometer allowing for subsecond acquisition times and the redesign of the delivery fiber and imaging optics in order to fit in the accessory channel of a gastroscope. Accurate sizing of polystyrene microspheres and other preliminary results are presented, demonstrating promise as a clinically viable tool.

Authors
Terry, NG; Zhu, Y; Brown, WJ; Wax, A
MLA Citation
Terry, NG, Zhu, Y, Brown, WJ, and Wax, A. "Development of a clinical Fourier-domain angle resolved low coherence interferometry system for in vivo measurements." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6864 (2008).
Source
scival
Published In
Proceedings of SPIE
Volume
6864
Publish Date
2008
DOI
10.1117/12.763782

Multiplexed low-coherence interferometry instrument for measuring microbicide gel thickness distribution

We present a multiplexed low coherence interferometry (LCI) system for in vivo human vaginal imaging of microbicidal gel distribution. In vitro testing demonstrated high accuracy and linearity of LCI in measuring gel coating thickness up to 500um. © 2007 Optical Society of America.

Authors
Drake, T; Robles, F; Wax, A
MLA Citation
Drake, T, Robles, F, and Wax, A. "Multiplexed low-coherence interferometry instrument for measuring microbicide gel thickness distribution." Biomedical Optics, BIOMED 2008 (2008): BMD81-.
Source
scival
Published In
Biomedical Optics, BIOMED 2008
Publish Date
2008
Start Page
BMD81

Modeling advances for measuring spheroidal geometries using angle-resolved low coherence interferometry

The relative efficacy of a modified Mie theory model and a T-matrix method model in determining the geometry of spheroidal scatterers is determined through comparison of scattering distributions of optical phantoms to these two models. © 2007 Optical Society of America.

Authors
Amoozegar, C; Giacomelli, MG; Chalut, KJ; Wax, A
MLA Citation
Amoozegar, C, Giacomelli, MG, Chalut, KJ, and Wax, A. "Modeling advances for measuring spheroidal geometries using angle-resolved low coherence interferometry." Biomedical Optics, BIOMED 2008 (2008): BTuF7-.
Source
scival
Published In
Biomedical Optics, BIOMED 2008
Publish Date
2008
Start Page
BTuF7

Design and verification of an endoscopic pre-cancer detection system based on angle-resolved low coherence interferometry (a/LCI)

This paper presents the design and implementation of a portable endoscopic a/LCI system for clinical pre-cancer detection through accurate sizing of cell nuclei. System performance is evaluated in ex vivo measurements. ©2007 Optical Society of America.

Authors
Zhu, Y; Terry, NG; Brown, WJ; Wax, A
MLA Citation
Zhu, Y, Terry, NG, Brown, WJ, and Wax, A. "Design and verification of an endoscopic pre-cancer detection system based on angle-resolved low coherence interferometry (a/LCI)." Biomedical Optics, BIOMED 2008 (2008): BTuC8-.
Source
scival
Published In
Biomedical Optics, BIOMED 2008
Publish Date
2008
Start Page
BTuC8

A comparison of mie theory and the t-matrix method for estimating the size of cell nuclei

We investigate the accuracy of inverse light scattering cell nuclei size predictions derived from Mie theory with the T-matrix method over a range of aspherical nuclei relevant to cancer detection and monitoring. © 2007 Optical Society of America.

Authors
Giacomelli, M; Chalut, K; Wax, A
MLA Citation
Giacomelli, M, Chalut, K, and Wax, A. "A comparison of mie theory and the t-matrix method for estimating the size of cell nuclei." Biomedical Optics, BIOMED 2008 (2008): BTuF6-.
Source
scival
Published In
Biomedical Optics, BIOMED 2008
Publish Date
2008
Start Page
BTuF6

Darkfield microspectroscopy: From single nanoparticle biosensing to live cell molecular imaging

Darkfield microspectroscopy enables detailed studies of the plasmonic features of noble metal nanoparticles. Shifts of the plasmon resonance of individual nanoparticles can be exploited for sensing applications or to achieve molecular imaging using targeted immunolabelling. © 2007 Optical Society of America.

Authors
Wax, A
MLA Citation
Wax, A. "Darkfield microspectroscopy: From single nanoparticle biosensing to live cell molecular imaging." Biomedical Optics, BIOMED 2008 (2008): BSuA2-.
Source
scival
Published In
Biomedical Optics, BIOMED 2008
Publish Date
2008
Start Page
BSuA2

Development of a novel hyperspectral darkfield microscopy system for characterization of nanoparticle sensors

We present a novel hyperspectral darkfield microscopy scheme that utilizes an epiillumination light train for improved characterization of the sensing capacity of noble metal nanoparticles. Validation experiments are presented to characterize the new system. © 2008 OSA/BIOMED/DH/LACSEA 2008.

Authors
Crow, M; Wax, A
MLA Citation
Crow, M, and Wax, A. "Development of a novel hyperspectral darkfield microscopy system for characterization of nanoparticle sensors." Biomedical Optics, BIOMED 2008 (2008): BSuE6-.
Source
scival
Published In
Biomedical Optics, BIOMED 2008
Publish Date
2008
Start Page
BSuE6

Progress in Biomedical Optics and Imaging - Proceedings of SPIE: Introduction

Authors
Wax, A; Backman, V
MLA Citation
Wax, A, and Backman, V. "Progress in Biomedical Optics and Imaging - Proceedings of SPIE: Introduction." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6446 (August 31, 2007).
Source
scopus
Published In
Proceedings of SPIE
Volume
6446
Publish Date
2007

Analysis of total uncertainty in spectral peak measurements for plasmonic nanoparticle-based biosensors.

One goal of recent research on plasmonic nanoparticle-based sensors is maximizing nanoparticle sensitivity or shift of resonance peak wavelength per refractive index change. Equally important is a measurement system's peak location uncertainty or shift resolution. We provide systematic analyses and discuss optimization of factors that determine peak location uncertainty, reporting values as low as 0.3 nm for the presented scheme. This type of analysis is important, in part, because it provides a means of evaluating detection thresholds for biosensor applications such as analyte binding. We estimate thresholds of 310 streptavidin molecules for the presented scheme and 20 molecules with system improvements.

Authors
Curry, A; Nusz, G; Chilkoti, A; Wax, A
MLA Citation
Curry, A, Nusz, G, Chilkoti, A, and Wax, A. "Analysis of total uncertainty in spectral peak measurements for plasmonic nanoparticle-based biosensors." Appl Opt 46.10 (April 1, 2007): 1931-1939.
PMID
17356640
Source
pubmed
Published In
Applied Optics
Volume
46
Issue
10
Publish Date
2007
Start Page
1931
End Page
1939

Molecular imaging and microspectroscopy of live cells using immunotargeted nanoparticles

We compare the expression of EGFR by epithelial carcinoma and neuroepithelial tumor cell lines, using hyperspectral darkfield microscopy to measure the scattering spectra of immunolabeled plasmonic nanoparticles bound by cell surface receptors. © 2007 OSA.

Authors
Wax, A; Crow, M
MLA Citation
Wax, A, and Crow, M. "Molecular imaging and microspectroscopy of live cells using immunotargeted nanoparticles." Optics InfoBase Conference Papers (January 1, 2007).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2007

Molecular imaging of EGFR expression in live cancer cells using immunotargeted nanoparticles

Using molecular imaging of immunolabeled plasmonic nanoparticles bound by cell surface receptors, we compare epidermal growth factor receptor expression, an indicator of cancerous activity, of both human epithelial carcinoma and brain tumor cell lines. © 2007 OSA/CLEO 2007.

Authors
Crow, M; Curry, A; Wax, A
MLA Citation
Crow, M, Curry, A, and Wax, A. "Molecular imaging of EGFR expression in live cancer cells using immunotargeted nanoparticles." Optics InfoBase Conference Papers (2007).
Source
scival
Published In
Optics InfoBase Conference Papers
Publish Date
2007

Quantitative phase microscopy with asynchronous digital holography system

We demonstrate a new method of measuring quantitative phase in biological materials. The method utilizes asynchronous digital holography, which uses a moving fringe created by acousto-optic modulators. Results are demonstrated on live cell samples © 2007 OSA/CLEO 2007.

Authors
Chalut, K; Brown, W; Terry, N; Wax, A
MLA Citation
Chalut, K, Brown, W, Terry, N, and Wax, A. "Quantitative phase microscopy with asynchronous digital holography system." Optics InfoBase Conference Papers (2007).
Source
scival
Published In
Optics InfoBase Conference Papers
Publish Date
2007

Development of a pre-clinical Fourier domain low coherence interferometry system

Authors
Graf, RN; Wax, A
MLA Citation
Graf, RN, and Wax, A. "Development of a pre-clinical Fourier domain low coherence interferometry system." 2007.
Source
wos-lite
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
6446
Publish Date
2007
DOI
10.1117/.12.699373

Application of Mie theory to determine the structure of spheroidal scatterers in biological materials

We present here the results of a numerical study on light scattering from nonspherical particles with relevance to detecting precancerous states in epithelial tissues. In previous studies of epithelial cell nuclei, the experimental light scattering data have been analyzed by comparison with Mie theory. However, given the spheroidal shape of many cell nuclei, the validity of this assumption demands a thorough investigation. We investigate this assumption by using the T-matrix method to model light scattered from spheroids with parameters relevant to epithelial cell nuclei. In our previous studies, we have developed a data analysis procedure that extracts the oscillatory component of the angular-scattering distribution for an ensemble of epithelial cell nuclei for comparison with Mie theory. We demonstrate that application of our analysis procedure to the predictions of the T-matrix method for spheroids, oriented such that their axis of symmetry is aligned with the incident light propagation direction, generally yields the spheroid dimension that is transverse to the incident light propagation direction with subwavelength accuracy. © 2007 Optical Society of America.

Authors
Keener, JD; Chalut, KJ; Pyhtila, JW; Wax, A
MLA Citation
Keener, JD, Chalut, KJ, Pyhtila, JW, and Wax, A. "Application of Mie theory to determine the structure of spheroidal scatterers in biological materials." Optics Letters 32.10 (2007): 1326-1328.
PMID
17440576
Source
scival
Published In
Optics Letters
Volume
32
Issue
10
Publish Date
2007
Start Page
1326
End Page
1328
DOI
10.1364/OL.32.001326

In situ detection of nuclear atypia in Barrett's esophagus by using angle-resolved low-coherence interferometry

Background: Monitoring of patients with Barrett's esophagus (BE) for dysplasia, currently done by systematic biopsy, can be improved through increasing the proportion of at-risk tissue examined. Objective: Optical biopsy techniques, which do not remove the tissue but interrogate the tissue with light, offer a potential method to improve the monitoring of BE. Frequency-domain angle resolved low-coherence interferometry (fa/LCI) is an optical spectroscopic technique applied through an endoscopic fiber bundle and measures the depth-resolved nuclear morphology of tissue, a key biomarker for identifying dysplasia. The aim of the study was to assess the diagnostic capability of fa/LCI for differentiating healthy and dysplastic tissue in patients with BE. Methods: Depth-resolved angular scattering data are acquired by using fa/LCI from tissue excised from 3 patients who had esophagogastrectomy. The data are processed to determine the average nuclear size and density as a function of depth beneath the tissue surface. These data are compared with the pathologic classification of the tissue. Main Outcome Measurements: Average of depth-resolved nuclear diameter and nuclear density measurements in tissue samples. Results: Upon comparison to pathologic diagnosis, the fa/LCI data results report the nuclear atypia characteristic of dysplasia in the epithelial tissue. Examination of the average nuclear morphology over the superficial 150 μm results in complete separation between healthy columnar and BE dysplastic tissues. Limitations: Lack of in vivo data; lack of nondysplastic BE data because of limited sample size. Conclusions: In complicated tissue structures, such as BE, depth-resolved nuclear morphology measurements provided an excellent means to identify dysplasia. The preliminary results demonstrate the great potential for the in vivo application of fa/LCI as a targeting mechanism for physical biopsy in patients with BE. © 2007 American Society for Gastrointestinal Endoscopy.

Authors
Pyhtila, JW; Chalut, KJ; Boyer, JD; Keener, J; D'Amico, T; Gottfried, M; Gress, F; Wax, A
MLA Citation
Pyhtila, JW, Chalut, KJ, Boyer, JD, Keener, J, D'Amico, T, Gottfried, M, Gress, F, and Wax, A. "In situ detection of nuclear atypia in Barrett's esophagus by using angle-resolved low-coherence interferometry." Gastrointestinal Endoscopy 65.3 (2007): 487-491.
PMID
17321252
Source
scival
Published In
Gastrointestinal Endoscopy
Volume
65
Issue
3
Publish Date
2007
Start Page
487
End Page
491
DOI
10.1016/j.gie.2006.10.016

Temporal coherence and time-frequency distributions in spectroscopic optical coherence tomography

Traditional analysis of spectroscopic optical coherence tomography (SOCT) signals is limited by an uncertainty relationship between time (depth) and frequency (wavelength). The use of a bilinear time-frequency distribution for analysis, such as those that compose Cohen's class of functions, may provide a way to avoid this limitation. Here we present the relationship between traditional SOCT analysis and the relevant Cohen class functions: the Wigner and Choi-Williams distributions. While cross terms that arise in these bilinear time-frequency distributions have been viewed as an artifact, here we identify these terms with temporal coherence, which contains significant information about the signal through phase relationships. The utility of time-frequency distributions is illustrated through analysis of calculated signals. © 2007 Optical Society of America.

Authors
Graf, RN; Wax, A
MLA Citation
Graf, RN, and Wax, A. "Temporal coherence and time-frequency distributions in spectroscopic optical coherence tomography." Journal of the Optical Society of America A: Optics and Image Science, and Vision 24.8 (2007): 2186-2195.
PMID
17621322
Source
scival
Published In
Journal of the Optical Society of America A
Volume
24
Issue
8
Publish Date
2007
Start Page
2186
End Page
2195
DOI
10.1364/JOSAA.24.002186

In situ assessment of intraepithelial neoplasia in hamster trachea epithelium using angle-resolved low-coherence interferometry

Optical spectroscopy was used to evaluate the transformation of nuclear morphology associated with intraepithelial neoplasia in an animal model of carcinogenesis. In this pilot study, we have assessed the capability of angle-resolved low-coherence interferometry (a/LCI) to monitor in situ the neoplastic progression of hamster trachea epithelial tissue. By using the depth resolution made possible by coherence gating, the a/LCI system has been adapted to the unique geometry of the hamster trachea to allow us to extract useful nuclear morphometric information from cells in the epithelial layer without the need for exogenous staining or tissue fixation. Analysis of a/LCI nuclear morphology measurements has identified two important biomarkers of neoplastic transformation in hamster trachea epithelium, the size and the refractive index of epithelial cell nuclei. By comparing the a/LCI measurements of these two biomarkers to pathologic classification, we distinguished nuclear morphology changes for normal tissue, low-grade dysplasia, and high-grade dysplasia. Given its previous usefulness for tracking neoplastic change through nuclear morphometry measurements, the a/LCI technique may prove to be a useful tool in evaluating chemopreventive agents in future studies of hamster trachea epithelium. Copyright © 2007 American Association for Cancer Research.

Authors
Chalut, KJ; Kresty, LA; Pyhtila, JW; Nines, R; Baird, M; Steele, VE; Wax, A
MLA Citation
Chalut, KJ, Kresty, LA, Pyhtila, JW, Nines, R, Baird, M, Steele, VE, and Wax, A. "In situ assessment of intraepithelial neoplasia in hamster trachea epithelium using angle-resolved low-coherence interferometry." Cancer Epidemiology Biomarkers and Prevention 16.2 (2007): 223-227.
PMID
17301253
Source
scival
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
16
Issue
2
Publish Date
2007
Start Page
223
End Page
227
DOI
10.1158/1055-9965.EPI-06-0418

Polarization effects on scatterer sizing accuracy analyzed with frequency-domain angle-resolved low-coherence interferometry

Angle-resolved low-coherence interferometry (a/LCI) enables us to make depth-resolved measurements of scattered light that can be used to recover subsurface structural information such as the size of cell nuclei. Endoscopic frequency-domain a/LCI (fa/LCI) acquires data by using a novel fiber probe in a fraction of a second, making it a clinically practical system. However, birefringent effects in fiber-based systems can alter the polarization state of the incident light and potentially skew the collected data. We analyze the effect the polarization state of the incident light has on scattering data collected from polystyrene microsphere tissue phantoms and in vitro cell samples and examine the subsequent accuracy of the determined sizes. It is shown that the endoscopic fa/LCI system accurately determines the size of polystyrene microspheres without the need to control the polarization of the incident beam, but that epithelial cell nuclear sizes are accurately determined only when the polarization state of the incident light is well characterized. © 2007 Optical Society of America.

Authors
Pyhtila, JW; Wax, A
MLA Citation
Pyhtila, JW, and Wax, A. "Polarization effects on scatterer sizing accuracy analyzed with frequency-domain angle-resolved low-coherence interferometry." Applied Optics 46.10 (2007): 1735-1741.
PMID
17356616
Source
scival
Published In
Applied Optics
Volume
46
Issue
10
Publish Date
2007
Start Page
1735
End Page
1741
DOI
10.1364/AO.46.001735

Quantitative phase microscopy with asynchronous digital holography

We demonstrate a new method of measuring quantitative phase in imaging of biological materials. This method, asynchronous digital holography, employs knowledge of a moving fringe created by acousto-optic modulators to execute phase-shifting interferometry using two near-simultaneous interferograms. The method can be used to obtain quantitative phase images of dynamic biological samples on millisecond time scales. We present results on a standard sample, and on live cell samples. © 2007 Optical Society of America.

Authors
Chalut, KJ; Brown, WJ; Wax, A
MLA Citation
Chalut, KJ, Brown, WJ, and Wax, A. "Quantitative phase microscopy with asynchronous digital holography." Optics Express 15.6 (2007): 3047-3052.
PMID
19532543
Source
scival
Published In
Optics express
Volume
15
Issue
6
Publish Date
2007
Start Page
3047
End Page
3052
DOI
10.1364/OE.15.003047

Workshop on imaging science development for cancer prevention and preemption.

The concept of intraepithelial neoplasm (IEN) as a near-obligate precursor of cancers has generated opportunities to examine drug or device intervention strategies that may reverse or retard the sometimes lengthy process of carcinogenesis. Chemopreventive agents with high therapeutic indices, well-monitored for efficacy and safety, are greatly needed, as is development of less invasive or minimally disruptive visualization and assessment methods to safely screen nominally healthy but at-risk patients, often for extended periods of time and at repeated intervals. Imaging devices, alone or in combination with anticancer drugs, may also provide novel interventions to treat or prevent precancer.

Authors
Kelloff, GJ; Sullivan, DC; Baker, H; Clarke, LP; Nordstrom, R; Tatum, JL; Dorfman, GS; Jacobs, P; Berg, CD; Pomper, MG; Birrer, MJ; Tempero, M; Higley, HR; Petty, BG; Sigman, CC; Maley, C; Sharma, P; Wax, A; Ginsberg, GG; Dannenberg, AJ; Hawk, ET; Messing, EM; Grossman, HB; Harisinghani, M; Bigio, IJ; Griebel, D; Henson, DE; Fabian, CJ; Ferrara, K; Fantini, S; Schnall, MD; Zujewski, JA; Hayes, W; Klein, EA; DeMarzo, A; Ocak, I; Ketterling, JA; Tempany, C; Shtern, F; Parnes, HL; Gomez, J et al.
MLA Citation
Kelloff, GJ, Sullivan, DC, Baker, H, Clarke, LP, Nordstrom, R, Tatum, JL, Dorfman, GS, Jacobs, P, Berg, CD, Pomper, MG, Birrer, MJ, Tempero, M, Higley, HR, Petty, BG, Sigman, CC, Maley, C, Sharma, P, Wax, A, Ginsberg, GG, Dannenberg, AJ, Hawk, ET, Messing, EM, Grossman, HB, Harisinghani, M, Bigio, IJ, Griebel, D, Henson, DE, Fabian, CJ, Ferrara, K, Fantini, S, Schnall, MD, Zujewski, JA, Hayes, W, Klein, EA, DeMarzo, A, Ocak, I, Ketterling, JA, Tempany, C, Shtern, F, Parnes, HL, and Gomez, J et al. "Workshop on imaging science development for cancer prevention and preemption." Cancer Biomark 3.1 (2007): 1-33.
PMID
17655039
Source
pubmed
Published In
Cancer biomarkers : section A of Disease markers
Volume
3
Issue
1
Publish Date
2007
Start Page
1
End Page
33

Quantitative phase microscopy with asynchronous digital holography system

We demonstrate a new method of measuring quantitative phase in biological materials. The method utilizes asynchronous digital holography, which uses a moving fringe created by acousto-optic modulators. Results are demonstrated on live cell samples. © OSA.

Authors
Chalut, K; Brown, W; Terry, N; Wax, A
MLA Citation
Chalut, K, Brown, W, Terry, N, and Wax, A. "Quantitative phase microscopy with asynchronous digital holography system." Conference on Lasers and Electro-Optics, 2007, CLEO 2007 (2007).
Source
scival
Published In
Conference on Lasers and Electro-Optics, 2007, CLEO 2007
Publish Date
2007
DOI
10.1109/CLEO.2007.4453094

Molecular imaging of EGFR expression in live cancer cells using immunotargeted nanoparticles

Using molecular imaging of immunolabeled plasmonic nanoparticles bound by cell surface receptors, we compare epidermal growth factor receptor expression, an indicator of cancerous activity, of both human epithelial carcinoma and brain tumor cell lines. ©OSA 1-55752-834-9.

Authors
Crow, M; Curry, A; Wax, A
MLA Citation
Crow, M, Curry, A, and Wax, A. "Molecular imaging of EGFR expression in live cancer cells using immunotargeted nanoparticles." Conference on Lasers and Electro-Optics, 2007, CLEO 2007 (2007).
Source
scival
Published In
Conference on Lasers and Electro-Optics, 2007, CLEO 2007
Publish Date
2007
DOI
10.1109/CLEO.2007.4452483

Development of a pre-clinical Fourier domain low coherence interferometry system

Fourier domain low coherence interferometry (fLCI) is an optical technique which combines the depth resolution of low coherence interferometry with the sensitivity of light scattering spectroscopy. The fLCI system uses a white light source in a modified Michelson interferometer with a spectrograph for detection of the mixed signal and reference fields. Depth-resolved structural information is recovered by performing a short-time Fourier transform on the detected spectrum, similar to spectroscopic optical coherence tomography, and analyzing the wavelength dependent variations in scattered light as a function of depth. fLCI has been demonstrated as an excellent technique for probing the nuclear morphology of a monolayer of in vitro cancer cells. We have built a new fLCI optical system which implements an imaging spectrograph for detection and a 4F interferometer which uses a 4-F imaging system to re-image light scattered from the experimental sample onto the slit of the imaging spectrograph. The new system has allowed us to measure light scattered from the deepest layers of thick scattering samples, such as tissue phantoms and thick animal tissues, for the first time. We now take the first steps to quantitatively determine the diameter of scatterers within a thick experimental sample using the new fLCI system along with the fLCI data processing technique.

Authors
Graf, RN; Wax, A
MLA Citation
Graf, RN, and Wax, A. "Development of a pre-clinical Fourier domain low coherence interferometry system." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6446 (2007).
Source
scival
Published In
Proceedings of SPIE
Volume
6446
Publish Date
2007
DOI
10.1117/12.699373

Development of a portable frequency-domain angle-resolved low coherence interferometry system

Improved methods for detecting dysplasia, or pre-cancerous growth, are a current clinical need. Random biopsy and subsequent diagnosis through histological analysis is the current gold standard in endoscopic surveillance for dysplasia. However, this approach only allows limited examination of the at-risk tissue and has the drawback of a long delay in time-to-diagnosis. In contrast, optical scattering spectroscopy methods offer the potential to assess cellular structure and organization in vivo, thus allowing for instantaneous diagnosis and increased coverage of the at-risk tissue. Angle-resolved low coherence interferometry (a/LCI), a novel scattering spectroscopy technique, combines the ability of low-coherence interferometry to isolate scattered light from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales, specifically by analyzing the angular distribution of the backscattered light. In application to examining tissue. a/LCI enables depth-resolved quantitative measurements of changes in the size and texture of cell nuclei, which are characteristic biomarkers of dysplasia. The capabilities of a/LCI were demonstrated initially by detecting pre-cancerous changes in epithelial cells within intact, unprocessed, animal tissues. Recently, we have developed a new frequency-domain a/LCI system, with sub-second acquisition time and a novel fiber optic probe. Preliminary results using the fa/LCI system to examine human esophageal tissue in Barrett's esophagus patients demonstrate the clinical viability of the approach. In this paper, we present a new portable system which improves upon the design of the fa/LCI system to allow for higher quality data to be collected in the clinic. Accurate sizing of polystyrene microspheres and cell nuclei from ex vivo human esophageal tissue is presented. These results demonstrate the promise of a/LCI as a clinically viable diagnostic tool.

Authors
Pyhtila, JW; Wax, A
MLA Citation
Pyhtila, JW, and Wax, A. "Development of a portable frequency-domain angle-resolved low coherence interferometry system." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6446 (2007).
Source
scival
Published In
Proceedings of SPIE
Volume
6446
Publish Date
2007
DOI
10.1117/12.699143

Progress in Biomedical Optics and Imaging - Proceedings of SPIE: Introduction

Authors
Wax, A; Backman, V
MLA Citation
Wax, A, and Backman, V. "Progress in Biomedical Optics and Imaging - Proceedings of SPIE: Introduction." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6446 (2007): ix-.
Source
scival
Published In
Proceedings of SPIE
Volume
6446
Publish Date
2007
Start Page
ix

Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry.

Angle-resolved low coherence interferometry (a/LCI) enables depth-resolved measurements of scattered light that can be used to recover subsurface structural information, such as the size of cell nuclei. Measurements of nuclear morphology, however, can be complicated by coherent scattering between adjacent cell nuclei. Previous studies have eliminated this component by applying a window filter to Fourier transformed angular data, based on the justification that the coherent scattering must necessarily occur over length scales greater than the cell size. To fully study this effect, results of experiments designed to test the validity of this approach are now presented. The a/LCI technique is used to examine light scattered by regular cell arrays, created using stamped adhesive micropatterned substrates. By varying the array spacing, it is demonstrated that cell-to-cell correlations have a predictable effect on light scattering distributions. These results are compared to image analysis of fluorescence micrographs of the cell array samples. The a/LCI results show that the impact of coherent scattering on nuclear morphology measurements can be eliminated through data filtering.

Authors
Pyhtila, JW; Ma, H; Simnick, AJ; Chilkoti, A; Wax, A
MLA Citation
Pyhtila, JW, Ma, H, Simnick, AJ, Chilkoti, A, and Wax, A. "Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry." J Biomed Opt 11.3 (May 2006): 34022-.
PMID
16822071
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
11
Issue
3
Publish Date
2006
Start Page
34022
DOI
10.1117/1.2209561

Measurement system for the high-throughput characterization of metal nanoparticles for biosensors

We present a system for the rapid characterization of nanoparticles for biosensors, providing concurrent atomic force microscopy and scattering spectra of individual nanoparticles and simultaneous spectra from various nanostructures created by electron beam lithography © 2005 Optical Society of America.

Authors
Curry, A; Nusz, G; Chilkoti, A; Wax, A
MLA Citation
Curry, A, Nusz, G, Chilkoti, A, and Wax, A. "Measurement system for the high-throughput characterization of metal nanoparticles for biosensors." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Optical scattering of confocal laser scanning reflectance microscopy in turbid media

We present quantitative analysis of optical scattering in confocal reflectance microscopy as a function of numerical aperture and scattering coefficient. Data is collected from samples of intralipid of varying concentration with objectives up to 1.4NA. © 2005 Optical Society of America.

Authors
Chou, DR; Wax, AP
MLA Citation
Chou, DR, and Wax, AP. "Optical scattering of confocal laser scanning reflectance microscopy in turbid media." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Endoscopic fourier-domain angle-resolved low coherence interferometry for assessing nuclear morphology in human epithelial tissues

Endoscopic Fourier-domain angle-resolved low coherence interferometry has been developed for depth resolved light scattering spectroscopy. System capabilities are demonstrated by determining the nuclei size in tissue phantoms, cell cultures and ex vivo human esophageal epithelium. © 2005 Optical Society of America.

Authors
Pyhtila, JW; Boyer, JD; Chalut, KJ; Wax, A
MLA Citation
Pyhtila, JW, Boyer, JD, Chalut, KJ, and Wax, A. "Endoscopic fourier-domain angle-resolved low coherence interferometry for assessing nuclear morphology in human epithelial tissues." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Epi-illumination darkfield through a microscope objective for imaging and spectral analysis of nanoparticle interaction with cells in culture

Existing darkfield illumination schemes are incompatible with many types of samples and/or procedures. We present a darkfield scheme which addresses these incompatibilities. We then apply the scheme to evaluate nanoparticles binding cancer cells in culture. © 2005 Optical Society of America.

Authors
Curry, A; Wax, A
MLA Citation
Curry, A, and Wax, A. "Epi-illumination darkfield through a microscope objective for imaging and spectral analysis of nanoparticle interaction with cells in culture." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Improved design of a heterodyne angle-resolved low coherence interferometry system used for new chemoprevention and carcinogenesis studies

Improvements have been made in existing angle-resolved interferometry system to enable greater accuracy and angular range for use in new chemopreventive/carcinogenic studies. © 2005 Optical Society of America.

Authors
Chalut, KJ; Pyhtila, JW; Wax, A
MLA Citation
Chalut, KJ, Pyhtila, JW, and Wax, A. "Improved design of a heterodyne angle-resolved low coherence interferometry system used for new chemoprevention and carcinogenesis studies." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Improved simulations for measuring microbicidal gel thickness using low-coherence interferometry

Spectral-domain low coherence interferometry is used to measure the thickness of microbicidal gels as applied to realistic tissue phantoms. Reflections originating between the gel and phantom are analyzed to give thickness measurements. © 2005 Optical Society of America.

Authors
Braun, KE; Wax, A
MLA Citation
Braun, KE, and Wax, A. "Improved simulations for measuring microbicidal gel thickness using low-coherence interferometry." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Multi-layer scattering tissue phantom for assessing angle-resolved low coherence interferometryprecancer diagnostic technique

Scattering tissue phantoms are developed for assessment of promising optical precancer diagnostic technique. The tissue phantoms provide a valuable evaluation method for the low-coherence interferometry technique. Size determination results and phantom relevance are examined. © 2005 Optical Society of America.

Authors
Boyer, JD; Pyhtila, JW; Wax, A
MLA Citation
Boyer, JD, Pyhtila, JW, and Wax, A. "Multi-layer scattering tissue phantom for assessing angle-resolved low coherence interferometryprecancer diagnostic technique." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Quantitative characterization of spectrograph entrance slit width on roll-off of fourier domain optical coherence tomography signals

The effect of spectrograph slit width on the depth sensitivity of Fourier domain optical coherence tomography is investigated. A relationship between the two is derived mathematically and supported experimentally. © 2005 Optical Society of America.

Authors
Braun, KE; Pyhtila, JW; Wax, A
MLA Citation
Braun, KE, Pyhtila, JW, and Wax, A. "Quantitative characterization of spectrograph entrance slit width on roll-off of fourier domain optical coherence tomography signals." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Sensitivity analysis of detecting plasmon resonance spectral shifts for nanoparticle based biosensors

Shifts in the plasmon resonance of single nanoparticles are being investigated for biosensing applications. A systematic analysis of the factors which influence uncertainties in the spectral data and a method for optimizing acquisition are presented. © 2005 Optical Society of America.

Authors
Curry, AC; Wax, A
MLA Citation
Curry, AC, and Wax, A. "Sensitivity analysis of detecting plasmon resonance spectral shifts for nanoparticle based biosensors." Optics InfoBase Conference Papers (January 1, 2006).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2006

Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection

Light scattered from biological tissues can exhibit an inverse power law spectral component. We develop a model based on the Born approximation and von Karman (self-affine) spatial correlation of submicron tissue refractive index to account for this. The model is applied to light scattering spectra obtained from excised esophagi of normal and carcinogen-treated rats. Power law exponents used to fit dysplastic tissue site spectra are significantly smaller than those from normal sites, indicating that changes in tissue self-affinity can serve as a potential biomarker for precancer. © 2006 The American Physical Society.

Authors
Hunter, M; Backman, V; Popescu, G; Kalashnikov, M; Boone, CW; Wax, A; Gopal, V; Badizadegan, K; Stoner, GD; Feld, MS
MLA Citation
Hunter, M, Backman, V, Popescu, G, Kalashnikov, M, Boone, CW, Wax, A, Gopal, V, Badizadegan, K, Stoner, GD, and Feld, MS. "Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection." Physical Review Letters 97.13 (2006).
PMID
17026078
Source
scival
Published In
Physical Review Letters
Volume
97
Issue
13
Publish Date
2006
DOI
10.1103/PhysRevLett.97.138102

Epi-illumination through the microscope objective applied to darkfield imaging and microspectroscopy of nanoparticle interaction with cells in culture

Existing darkfield illumination schemes are incompatible with many types of samples and/or procedures. We present a darkfield epiillumination scheme which addresses these incompatibilities by providing illumination through the imaging objective. We validate the system performance using silver nanospheres in varying refractive index environments, characterize the intensity distribution of the darkfield illumination, and demonstrate system capabilities through a preliminary study of functionalized gold nanosphere interactions with cancer cells in culture. We observe a broadened scattering spectrum from unconjugated nanoparticles, as compared with anti-EGFR conjugated nanoparticles, upon incubation with cancer cells, and discuss the implications of this observation. © 2006 Optical Society of America.

Authors
Curry, A; Hwang, WL; Wax, A
MLA Citation
Curry, A, Hwang, WL, and Wax, A. "Epi-illumination through the microscope objective applied to darkfield imaging and microspectroscopy of nanoparticle interaction with cells in culture." Optics Express 14.14 (2006): 6535-6542.
PMID
19516830
Source
scival
Published In
Optics express
Volume
14
Issue
14
Publish Date
2006
Start Page
6535
End Page
6542
DOI
10.1364/OE.14.006535

Label-free measurement of microbicidal gel thickness using lowcoherence interferometry

Spectral-domain low-coherence interferometry (LCI) was used to measure the thickness of microbicidal gels applied to a cylindrical calibration test socket. Microbicides are topical formulations containing active ingredients targeted to inhibit specific pathogens that are currently under development for application to the epithelial lining of the lower female reproductive tract to combat sexually transmitted infections such as HIV. Understanding the deployment and drug delivery of these formulations is vital to maximizing their effectiveness. Previously, in vivo measurements of microbicidal formulation thickness were assessed using fluorescence measurements of fluorescein-labeled gels via an optical endoscope-based device. Here we present an LCI-based device that measures the thickness of a formulation without the use of any exogenous agents by analyzing the interference pattern generated between the reflections from the front and back surface of the sample. Results are presented that validate the effectiveness and performance of the LCI measurement in a clinically relevant system as compared to an existing fluorescence-based method. The impact of the new LCI-based design on in vivo measurements is discussed. © 2006 Society of Photo-Optical Instrumentation Engineers.

Authors
Braun, KE; Boyer, JD; Henderson, MH; Katz, DF; Wax, A
MLA Citation
Braun, KE, Boyer, JD, Henderson, MH, Katz, DF, and Wax, A. "Label-free measurement of microbicidal gel thickness using lowcoherence interferometry." Journal of Biomedical Optics 11.2 (2006).
PMID
16674175
Source
scival
Published In
Journal of Biomedical Optics
Volume
11
Issue
2
Publish Date
2006
DOI
10.1117/1.2192767

Fourier-domain angle-resolved low coherence interferometry through an endoscopic fiber bundle for light-scattering spectroscopy

We present a novel endoscopic fiber bundle probe incorporated in a Fourier-domain angle-resolved low coherence interferometry system for the measurement of depth-resolved angular scattering distributions to permit the determination of scatterer size via elastic scattering properties. Depth resolution is achieved with a superluminescent diode via a Mach-Zehnder interferometer. The sample is illuminated with a collimated beam, and a Fourier plane image of the backscattered light is collected by a coherent fiber bundle. The angular scattering distribution relayed by the fiber bundle is mixed with the reference field and made to coincide with the input slit of an imaging spectrograph. The data collected are processed in real time, producing a depth-resolved angular scattering distribution in 0.37 s. The data are used to determine the sizes of polystyrene microspheres with subwavelength precision and accuracy. © 2006 Optical Society of America.

Authors
Pyhtila, JW; Boyer, JD; Chalut, KJ; Wax, A
MLA Citation
Pyhtila, JW, Boyer, JD, Chalut, KJ, and Wax, A. "Fourier-domain angle-resolved low coherence interferometry through an endoscopic fiber bundle for light-scattering spectroscopy." Optics Letters 31.6 (2006): 772-774.
PMID
16544619
Source
scival
Published In
Optics Letters
Volume
31
Issue
6
Publish Date
2006
Start Page
772
End Page
774
DOI
10.1364/OL.31.000772

Substrate effect on refractive index dependence of plasmon resonance for individual silver nanoparticles observed using darkfield microspectroscopy.

We use optical darkfield micro-spectroscopy to characterize the plasmon resonance of individual silver nanoparticles in the presence of a substrate. The optical system permits multiple individual nanoparticles to be identified visually for simultaneous spectroscopic study. For silver particles bound to a silanated glass substrate, we observe changes in the Plasmon resonance due to induced variations in the local refractive index. The shifts in the plasmon resonance are investigated using a simple analytical theory in which the contributions from the substrate and environment are weighted with distance from the nanoparticle. The theory is compared with experimental results to determine a weighting factor which facilitates modeling of environmental refractive index changes using standard Mie code. Use of the optical system for characterizing nanoparticles attached to substrates for biosensing applications is discussed.

Authors
Curry, A; Nusz, G; Chilkoti, A; Wax, A
MLA Citation
Curry, A, Nusz, G, Chilkoti, A, and Wax, A. "Substrate effect on refractive index dependence of plasmon resonance for individual silver nanoparticles observed using darkfield microspectroscopy." Opt Express 13.7 (April 4, 2005): 2668-2677.
PMID
19495158
Source
pubmed
Published In
Optics express
Volume
13
Issue
7
Publish Date
2005
Start Page
2668
End Page
2677

Measurement system for the high-throughput characterization of metal nanoparticles for biosensors

We present a system for the rapid characterization of nanoparticles for biosensors, providing concurrent atomic force microscopy and scattering spectra of individual nanoparticles and simultaneous spectra from various nanostructures created by electron beam lithography © 2005 Optical Society of America.

Authors
Curry, A; Nusz, G; Chilkoti, A; Wax, A
MLA Citation
Curry, A, Nusz, G, Chilkoti, A, and Wax, A. "Measurement system for the high-throughput characterization of metal nanoparticles for biosensors." Optics InfoBase Conference Papers (January 1, 2005).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2005

Optical scattering of confocal laser scanning reflectance microscopy in turbid media

We present quantitative analysis of optical scattering in confocal reflectance microscopy as a function of numerical aperture and scattering coefficient. Data is collected from samples of intralipid of varying concentration with objectives up to 1.4NA. © 2005 Optical Society of America.

Authors
Chou, DR; Wax, AP
MLA Citation
Chou, DR, and Wax, AP. "Optical scattering of confocal laser scanning reflectance microscopy in turbid media." Optics InfoBase Conference Papers (January 1, 2005).
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2005

Nuclear morphology measurements using Fourier domain low coherence interferometry

We have developed Fourier domain low coherence interferometry (fLCI), a novel optical interferometry method for obtaining depth-resolved spectral information, specifically for the purpose of determining the size of scatterers by measuring their elastic scattering properties. The optical system achieves depth resolution by using coherence gating, enabled by the use of a white light source in a Michelson interferometer and detection of the mixed signal and reference fields with a spectrograph. The measured spectrum is Fourier transformed to obtain the axial spatial cross-correlation between the signal and reference fields providing depth-resolution. The spectral dependence of scattering by the sample is determined by windowing the spectrum to measure the scattering amplitude as a function of wavenumber (k = 2 Pi / λ, where λ is the wavelength). We present a new common path confgiuration fLCI optical system and demonstrate its capabilities by presenting results which determine the size of cell nuclei in a monolayer of T84 epithelial cells.

Authors
Graf, RN; Wax, A
MLA Citation
Graf, RN, and Wax, A. "Nuclear morphology measurements using Fourier domain low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5690 (2005): 460-467.
Source
scival
Published In
Proceedings of SPIE
Volume
5690
Publish Date
2005
Start Page
460
End Page
467
DOI
10.1117/12.592227

Rapid angle-resolved low coherence interferometry measurements

We have developed a novel angle-resolved low coherence interferometry scheme for rapid measurement of depth-resolved angular scattering distributions. These measurements enable the determination of scatterer size via elastic scattering properties. The scheme uses spectral domain measurements where the mixed signal and reference fields are dispersed by an imaging spectrograph to achieve depth-resolved measurements upon Fourier transform of the spectral data. Angle-resolved measurements are obtained by locating the spectrograph slit in a Fourier transform plane of the scattering sample. We discuss the theoretical basis for the measurements and demonstrate the capabilities of the new technique by recording the distribution of light scattered by polystyrene microspheres. The important features of the system include the ability to detect sub-surface scattering distributions and rapid data acquisition with the entire scattering distribution recorded in 40 milliseconds. The data are used to determine the microsphere size with good accuracy. Potential application of the technique to measuring cell nuclei size in living epithelial tissues is discussed.

Authors
Pyhtila, JW; Wax, A
MLA Citation
Pyhtila, JW, and Wax, A. "Rapid angle-resolved low coherence interferometry measurements." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5690 (2005): 468-474.
Source
scival
Published In
Proceedings of SPIE
Volume
5690
Publish Date
2005
Start Page
468
End Page
474
DOI
10.1117/12.592012

Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry

Angle-resolved low-coherence interferometry (a/LCI) is used to obtain quantitative, depth-resolved nuclear morphology measurements. We compare the average diameter and texture of cell nuclei in rat esophagus epithelial tissue to grading criteria established in a previous a/LCI study to prospectively grade neoplastic progression. We exploit the depth resolution of a/LCI to exclusively examine the basal layer of the epithelium, approximately 50 to 100 μm beneath the tissue surface, without the need for exogenous contrast agents, tissue sectioning, or fixation. The results of two studies are presented that compare the performance of two a/LCI modalities. Overall, the combined studies show 91% sensitivity and 97% specificity for detecting dysplasia, using histopathology as the standard. In addition, the studies enable the effects of dietary chemopreventive agents, difluoromethylornithine (DFMO) and curcumin, to be assessed by observing modulation in the incidence of neoplastic change. We demonstrate that a/LCI is highly effective for monitoring neoplastic change and can be applied to assessing the efficacy of chemopreventive agents in the rat esophagus. © 2005 Society of Photo-Optical Instrumentation Engineers.

Authors
Wax, A; Pyhtila, JW; Graf, RN; Nines, R; Boone, CW; Dasari, RR; Feld, MS; Steele, VE; Stoner, GD
MLA Citation
Wax, A, Pyhtila, JW, Graf, RN, Nines, R, Boone, CW, Dasari, RR, Feld, MS, Steele, VE, and Stoner, GD. "Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry." Journal of Biomedical Optics 10.5 (2005).
PMID
16292952
Source
scival
Published In
Journal of Biomedical Optics
Volume
10
Issue
5
Publish Date
2005
DOI
10.1117/1.2102767

Nuclear morphology measurements using Fourier domain low coherence interferometry

We present a new common path configuration Fourier domain low coherence interferometry (fLCI) optical system and demonstrate its capabilities by presenting results which determine the size of cell nuclei in a monolayer of T84 epithelial cells. The optical system uses a white light source in a modified Michelson interferometer and a spectrograph for detection of the mixed signal and reference fields. Depth resolution is obtained from the Fourier transform of the measured spectrum which provides the axial spatial cross-correlation between the signal and reference fields. The spectral dependence of scattering by the samples is determined by windowing the spectrum to measure the scattering amplitude as a function of wavenumber. We present evidence that fLCI accurately measures the longitudinal profile of cell nuclei rather than the transverse profile. © 2005 Optical Society of America.

Authors
Graf, RN; Wax, A
MLA Citation
Graf, RN, and Wax, A. "Nuclear morphology measurements using Fourier domain low coherence interferometry." Optics Express 13.12 (2005): 4693-4698.
PMID
16429608
Source
scival
Published In
Optics express
Volume
13
Issue
12
Publish Date
2005
Start Page
4693
End Page
4698
DOI
10.1364/OPEX.13.004693

Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer

Harmonic phase-dispersion microscopy (PDM) is a new imaging technique in which contrast is provided by differences in refractive index at two harmonically related wavelengths. We report a new configuration of the harmonic phase-dispersion microscope in a Mach-Zehnder geometry as an instrument for imaging biological samples. Several improvements on the earlier design are demonstrated, including a single-pass configuration and acousto-optic modulators for generating the heterodyne signals without mechanical arm scanning. We demonstrate quantitative phase-dispersion images of test structures and biological samples. © 2005 Optical Society of America.

Authors
Ahn, A; Yang, C; Wax, A; Popescu, G; Fang-Yen, C; Badizadegan, K; Dasari, RR; Feld, MS
MLA Citation
Ahn, A, Yang, C, Wax, A, Popescu, G, Fang-Yen, C, Badizadegan, K, Dasari, RR, and Feld, MS. "Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer." Applied Optics 44.7 (2005): 1188-1190.
PMID
15765698
Source
scival
Published In
Applied Optics
Volume
44
Issue
7
Publish Date
2005
Start Page
1188
End Page
1190
DOI
10.1364/AO.44.001188

Low-cost, scalable laser scanning module for real-time reflectance and fluorescence confocal microscopy

We present a low-cost, high-speed, retrofitted laser scanning module for microscopy. The cage-mounted system, with various available fiber-coupled sources, offers a real-time imaging alternative to costly commercial systems with capabilities for conventional or confocal reflectance and fluorescence applications as well as advanced laser scanning microscopy implementations. Reflectance images of a resolution target and confocal images of fluorescent polystyrene beads are presented for system characterization. Confocal fluorescence image stacks of T84 epithelial cancer cells are presented to demonstrate application to biological studies. This laser scanning module is a flexible, scalable, high-speed alternative to commercial laser scanning systems suitable for applications requiring a simple imaging tool and for teaching laboratories. © 2005 Optical Society of America.

Authors
Chou, DR; Bower, BA; Wax, A
MLA Citation
Chou, DR, Bower, BA, and Wax, A. "Low-cost, scalable laser scanning module for real-time reflectance and fluorescence confocal microscopy." Applied Optics 44.11 (2005): 2013-2018.
PMID
15835349
Source
scival
Published In
Applied Optics
Volume
44
Issue
11
Publish Date
2005
Start Page
2013
End Page
2018
DOI
10.1364/AO.44.002013

Coherent light scattering by in vitro cell arrays observed with angle-resolved low coherence interferometry

Angle-resolved low coherence interferometry enables depth-resolved measurements of scattered light. The scattered light measurements can be used to recover structural information from sub-surface layers, such as the size of cell nuclei. Measurements of nuclear morphology, however, can be complicated by coherent scattering between adjacent cell nuclei. Previous studies have eliminated this component by applying a window filter to Fourier transformed data based upon the justification that the coherent scattering must necessarily occur over length scales greater than the cell nucleus size. To fully study this effect, we now present results of experiments designed to test the validity of this approach. We examine light scattered by regular cell arrays, created using stamped adhesive micro-patterned substrates. By varying the array spacing, the influence of cell-to-cell correlations on light scattering distributions is determined. The impact on nuclear morphology measurements within intact tissue samples is discussed.

Authors
Pyhtila, JW; Wax, A
MLA Citation
Pyhtila, JW, and Wax, A. "Coherent light scattering by in vitro cell arrays observed with angle-resolved low coherence interferometry." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5690 (2005): 334-341.
Source
scival
Published In
Proceedings of SPIE
Volume
5690
Publish Date
2005
Start Page
334
End Page
341
DOI
10.1117/12.592230

Low-coherence light-scattering calculations for polydisperse size distributions

The calculation of angular light-scattering distributions is considered for low-coherence light incident on a polydisperse particle size distribution of scatterers. As low-coherence light is now commonly used in interferometry schemes when applied to biomedical imaging, the difference between detecting scattered intensity and interferometrically detecting the scattered field is examined. An expression is derived that allows the presence of multiple wavelengths λ and particle sizes d to be described by a single distribution in the size parameter x = πd/λ, which simplifies numerical calculations. The applicability of this expression is examined numerically. © 2005 Optical Society of America.

Authors
Wax, A
MLA Citation
Wax, A. "Low-coherence light-scattering calculations for polydisperse size distributions." Journal of the Optical Society of America A: Optics and Image Science, and Vision 22.2 (2005): 256-261.
PMID
15717554
Source
scival
Published In
Journal of the Optical Society of America A
Volume
22
Issue
2
Publish Date
2005
Start Page
256
End Page
261
DOI
10.1364/JOSAA.22.000256

Improved interferometric detection of scattered light with a 4f imaging system

We analyze the performance of three imaging systems to detect near-forward scattered light interfero-metrically by using a Mach-Zehnder geometry. The alignment of each system is demonstrated by measurement of the heterodyne efficiency and correlation of the angular width and field 1/e radius measurements of the sample beam. Measurements of angular-scattering data demonstrate the range of angles over which each system is effective. Of the three systems analyzed, the 4f imaging system is determined to be most effective, because it accurately reproduces both the phase and the amplitude of the scattered field at the detector. © 2005 Optical Society of America.

Authors
Pyhtila, JW; Wax, A
MLA Citation
Pyhtila, JW, and Wax, A. "Improved interferometric detection of scattered light with a 4f imaging system." Applied Optics 44.10 (2005): 1785-1791.
PMID
15813513
Source
scival
Published In
Applied Optics
Volume
44
Issue
10
Publish Date
2005
Start Page
1785
End Page
1791
DOI
10.1364/AO.44.001785

Optical scattering of confocal laser scanning reflectance microscopy in turbid media

We present quantitative analysis of optical scattering in confocal reflectance microscopy as a function of numerical aperture and scattering coefficient. Data is collected from samples of intralipid of varying concentration with objectives up to 1.4NA. © 2005 Optical Society of America.

Authors
Chov, DR; Wax, AP
MLA Citation
Chov, DR, and Wax, AP. "Optical scattering of confocal laser scanning reflectance microscopy in turbid media." 2005 Conference on Lasers and Electro-Optics, CLEO 3 (2005): 1578-1580.
Source
scival
Published In
2005 Conference on Lasers and Electro-Optics, CLEO
Volume
3
Publish Date
2005
Start Page
1578
End Page
1580

Measurement system for the high-throughput characterization of metal nanoparticles for biosensors

We present a system for the rapid characterization of nanoparticles for biosensors, providing concurrent atomic force microscopy and scattering spectra of individual nanoparticles and simultaneous spectra from various nanostructures created by electron beam lithography. © 2005 Optical Society of America.

Authors
Curry, A; Nusz, G; Chilkoti, A; Wax, A
MLA Citation
Curry, A, Nusz, G, Chilkoti, A, and Wax, A. "Measurement system for the high-throughput characterization of metal nanoparticles for biosensors." 2005 Conference on Lasers and Electro-Optics, CLEO 3 (2005): 2160-2162.
Source
scival
Published In
2005 Conference on Lasers and Electro-Optics, CLEO
Volume
3
Publish Date
2005
Start Page
2160
End Page
2162

Quantitative phase imaging using actively stabilized phase-shifting low-coherence interferometry

We describe a quantitative phase-imaging interferometer in which phase shifting and noise cancellation are performed by an active feedback loop using a reference laser. Depth gating via low-coherence light allows phase measurement from weakly reflecting biological samples. We demonstrate phase images from a test structure and living cells. © 2004 Optical Society of America.

Authors
Iwai, H; Fang-Yen, C; Popescu, G; Wax, A; Badizadegan, K; Dasari, RR; Feld, MS
MLA Citation
Iwai, H, Fang-Yen, C, Popescu, G, Wax, A, Badizadegan, K, Dasari, RR, and Feld, MS. "Quantitative phase imaging using actively stabilized phase-shifting low-coherence interferometry." Optics Letters 29.20 (2004): 2399-2401.
PMID
15532280
Source
scival
Published In
Optics Letters
Volume
29
Issue
20
Publish Date
2004
Start Page
2399
End Page
2401
DOI
10.1364/OL.29.002399

Rapid, depth-resolved light scattering measurements using Fourier domain, angle-resolved low coherence interferometry

We present a novel angle-resolved low coherence interferometry scheme for rapid measurement of depth-resolved angular scattering distributions to enable determination of scatterer size via elastic scattering properties. Depth resolution is achieved using a superluminescent diode in a modified Mach-Zehnder interferometer with the mixed signal and reference fields dispersed by an imaging spectrograph. The spectrograph slit is located in a Fouriertransform plane of the scattering sample, enabling angle-resolved measurements over a 0.21 radian range. The capabilities of the new technique are demonstrated by recording the distribution of light scattered by a sub-surface layer of polystyrene microspheres in 40 milliseconds. The data are used to determine the microsphere size with good accuracy. Future clinical application to measuring the size of cell nuclei in living epithelial tissues using backscattered light is discussed. ©2004 Optical Society of America.

Authors
Pyhtila, JW; Wax, A
MLA Citation
Pyhtila, JW, and Wax, A. "Rapid, depth-resolved light scattering measurements using Fourier domain, angle-resolved low coherence interferometry." Optics Express 12.25 (2004): 6178-6183.
PMID
17195864
Source
scival
Published In
Optics express
Volume
12
Issue
25
Publish Date
2004
Start Page
6178
End Page
6183
DOI
10.1364/OPEX.12.006178

Fourier-domain low-coherence interferometry for light-scattering spectroscopy.

We present a novel method for obtaining depth-resolved spectra for determining scatterer size through elastic-scattering properties. Depth resolution is achieved with a white-light source in a Michelson interferometer with the mixed signal and reference fields dispersed by a spectrograph. The spectrum is Fourier transformed to yield the axial spatial cross correlation between the signal and reference fields with near 1-microm depth resolution. Spectral information is obtained by windowing to yield the scattering amplitude as a function of wave number. The technique is demonstrated by determination of the size of polystyrene microspheres in a subsurface layer with subwavelength accuracy. Application of the technique to probing the size of cell nuclei in living epithelial tissues is discussed.

Authors
Wax, A; Yang, C; Izatt, JA
MLA Citation
Wax, A, Yang, C, and Izatt, JA. "Fourier-domain low-coherence interferometry for light-scattering spectroscopy." Opt Lett 28.14 (July 15, 2003): 1230-1232.
PMID
12885030
Source
pubmed
Published In
Optics Letters
Volume
28
Issue
14
Publish Date
2003
Start Page
1230
End Page
1232

In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry.

We present a quantitative study of the nuclear morphometry of epithelial cells in an animal model of esophageal carcinogenesis. Changes in the size and texture of cell nuclei as a result of neoplastic transformation and chemopreventive action are observed in situ using a new optical technique, angle-resolved low-coherence interferometry (a/LCI). The capabilities of a/LCI are demonstrated via quantitative in situ measurements of the nuclear morphometry of basal epithelial cells, approximately 50-100 microm beneath the tissue surface without the need for exogenous contrast agents or tissue fixation. The measurements quantify changes in nuclear size, characterized by average diameter, and nuclear texture, characterized by fractal dimension of the subcellular structures. Using this technique, we observed changes in the morphometry of rat esophageal epithelial cells in response to treatment with the carcinogen N-nitrosomethylbenzylamine. In addition, morphometric changes were observed in the esophagi of rats treated with N-nitrosomethylbenzylamine and two chemopreventive agents, difluoromethylornithine and perillyl alcohol. These agents induced either apoptosis in the basal epithelium (difluoromethylornithine) or both apoptosis and vacuolation of basal epithelial cells (perillyl alcohol). Vacuolation was associated with cellular toxicity. The light-scattering measurements were compared with histological images of the same tissues. The potential of a/LCI as a noninvasive means to investigate the development of epithelial neoplasia and for tracking the efficacy of chemopreventive agents appears high. This technique also may provide a new screening tool for intraepithelial neoplasia.

Authors
Wax, A; Yang, C; Müller, MG; Nines, R; Boone, CW; Steele, VE; Stoner, GD; Dasari, RR; Feld, MS
MLA Citation
Wax, A, Yang, C, Müller, MG, Nines, R, Boone, CW, Steele, VE, Stoner, GD, Dasari, RR, and Feld, MS. "In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry." Cancer Res 63.13 (July 1, 2003): 3556-3559.
PMID
12839941
Source
pubmed
Published In
Cancer Research
Volume
63
Issue
13
Publish Date
2003
Start Page
3556
End Page
3559

Determining nuclear morphology using an improved angle-resolved low coherence interferometry system

We outline the process for determining the morphology of sub-surface epithelial cell nuclei using depth-resolved light scattering measurements. The measurements are accomplished using a second generation angle-resolved low coherence interferometry system. The new system greatly improves data acquisition and analysis times compared to the initial prototype system. The calibration of the new system is demonstrated in scattering studies to determine the size distribution of polystyrene microspheres in a turbid sample. The process for determining the size of cell nuclei is discussed by analyzing measurements of basal cells in a sub-surface layer of intact, unstained epithelial tissue. © 2003 Optical Society of America.

Authors
Pyhtila, JW; Graf, RN; Wax, A
MLA Citation
Pyhtila, JW, Graf, RN, and Wax, A. "Determining nuclear morphology using an improved angle-resolved low coherence interferometry system." Optics Express 11.25 (2003): 3473-3484.
PMID
19471481
Source
scival
Published In
Optics express
Volume
11
Issue
25
Publish Date
2003
Start Page
3473
End Page
3484

Instrumentation for Multi-modal Spectroscopic Diagnosis of Epithelial Dysplasia

Reflectance and fluorescence spectroscopies have shown great promise for early detection of epithelial dysplasia. We have developed a clinical reflectance spectrofluorimeter for multimodal spectroscopic diagnosis of epithelial dysplasia. This clinical instrument, the FastEEM, collects white light reflectance and fluorescence excitation-emission matrices (EEM's) within a fraction of a second. In this paper we describe the FastEEM instrumentation, designed for collection of multi-modal spectroscopic data. We illustrate its performance using tissue phantoms with well defined optical properties and biochemicals of known fluorescence properties. In addition, we discuss our plans to develop a system that combines a multi-spectral imaging device for wide area surveillance with this contact probe device.

Authors
Tunnell, JW; Desjardins, AE; Galindo, L; Georgakoudi, I; McGee, SA; Mirkovic, J; Mueller, MG; Nazemi, J; Nguyen, FT; Wax, A; Zhang, Q; Dasari, RR; Feld, MS
MLA Citation
Tunnell, JW, Desjardins, AE, Galindo, L, Georgakoudi, I, McGee, SA, Mirkovic, J, Mueller, MG, Nazemi, J, Nguyen, FT, Wax, A, Zhang, Q, Dasari, RR, and Feld, MS. "Instrumentation for Multi-modal Spectroscopic Diagnosis of Epithelial Dysplasia." Technology in Cancer Research and Treatment 2.6 (2003): 505-514.
PMID
14640762
Source
scival
Published In
Technology in Cancer Research and Treatment
Volume
2
Issue
6
Publish Date
2003
Start Page
505
End Page
514

A reflectance spectrofluorimeter for real-time spectral diagnosis of disease

Authors
Müller, MG; Wax, A; Georgakoudi, I; Dasari, RR; Feld, MS
MLA Citation
Müller, MG, Wax, A, Georgakoudi, I, Dasari, RR, and Feld, MS. "A reflectance spectrofluorimeter for real-time spectral diagnosis of disease." Review of Scientific Instruments 73.11 (2002): 3933--.
Source
scival
Published In
Review of Scientific Instruments
Volume
73
Issue
11
Publish Date
2002
Start Page
3933-
DOI
10.1063/1.1511795

Determination of particle size by using the angular distribution of backscattered light as measured with low-coherence interferometry

We employ a novel interferometer to measure the angular distribution of light backscattered by a turbid medium. Through comparison of the measured data with the predictions of Mie theory, we are able to determine the size of the scatterers comprising the medium with subwavelength precision. As the technique is based on low-coherence interferometry, we are able to examine the evolution of the angular distribution of scattered light as it propagates into the medium. The effects of multiple scattering as a function of penetration depth in the medium are analyzed. We also present various considerations for extending this technique to determining structural information in biological tissues, such as the effects of a distribution of particle sizes and the need to average out speckle contributions. © 2002 Optical Society of America.

Authors
Wax, A; Yang, C; Backman, V; Kalashnikov, M; Dasari, RR; Feld, MS
MLA Citation
Wax, A, Yang, C, Backman, V, Kalashnikov, M, Dasari, RR, and Feld, MS. "Determination of particle size by using the angular distribution of backscattered light as measured with low-coherence interferometry." Journal of the Optical Society of America A: Optics and Image Science, and Vision 19.4 (2002): 737-744.
PMID
11934166
Source
scival
Published In
Journal of the Optical Society of America A
Volume
19
Issue
4
Publish Date
2002
Start Page
737
End Page
744

2π ambiguity-free optical distance measurement with subnanometer precision with a novel phase-crossing low-coherence interferometer

We report a highly accurate phase-based technique for measuring arbitrarily long optical distance with subnanometer precision. The method employs a Michelson interferometer with a pair of harmonically related light sources, one cw and the other low coherence. By slightly detuning (~2 nm) the center wavelength of the low-coherence source between scans of the target sample, we can use the phase relationship between the heterodyne signals of the cw and the low-coherence light to measure the separation between reflecting interfaces with subnanometer precision. As this technique is completely free of 2π ambiguity, an issue that plagues most phase-based techniques, it can be used to measure arbitrarily long optical distances without loss of precision. We demonstrate one application of this technique, the high-precision determination of the differential refractive index

Authors
Yang, C; Wax, A; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Dasari, RR, and Feld, MS. "2π ambiguity-free optical distance measurement with subnanometer precision with a novel phase-crossing low-coherence interferometer." Opt. Lett. (USA) 27.2 (2002): 77-79. (Academic Article)
Source
manual
Published In
Opt. Lett. (USA)
Volume
27
Issue
2
Publish Date
2002
Start Page
77
End Page
79

The study of cell dynamics with a novel phase referenced low coherence interferometer with sub-wavelength and sub-hertz sensitivity

We report the use of a highly sensitive phase based motion measurement technique to study the correlation of cellular metabolic rate with cellular motions. The technique is based on a modified Michelson interferometer with a composite laser beam of 1550 nm low coherence light and 775 nm CW light. In this system, motional artifacts from vibrations in the interferometer are completely eliminated. We demonstrate that the system is sensitive to motions as small as 3.6 nm and velocities as small as 1 nm/s. Using the system, we show that the cellular motions are strongly dependent on the ambient temperature. We observe that the dependency does not conform to Brownian motion predictions but instead appears to correlate with the optical ambient temperature that the cells have evolved to operate in.

Authors
Yang, C; Wax, A; Badizadegan, K; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Badizadegan, K, Dasari, RR, and Feld, MS. "The study of cell dynamics with a novel phase referenced low coherence interferometer with sub-wavelength and sub-hertz sensitivity." Proceedings of SPIE - The International Society for Optical Engineering 4619 (2002): 202-209.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
4619
Publish Date
2002
Start Page
202
End Page
209
DOI
10.1117/12.470484

Cellular organization and substructure measured using angle-resolved low-coherence interferometry

We measure the organization and substructure of HT29 epithelial cells in a monolayer using angle-resolved low-coherence interferometry. This new technique probes cellular structure by measuring scattered light, as in flow cytometry, but offers an advantage in that the structure can be examined in situ, avoiding the need to disrupt the cell monolayer. We determine the size distribution of the cell nuclei by fitting measured light-scattering spectra to the predictions of Mie theory. In addition, we obtain information about the cellular organization and substructure by examining the spatial correlations within the monolayer. A remarkable finding is that the spatial correlations over small length scales take the form of an inverse power law, indicating the fractal nature of the packing of the subcellular structures. We also identify spatial correlations on a scale large compared with the size of a cell, indicating an overlying order within the monolayer.

Authors
Wax, A; Yang, C; Backman, V; Badizadegan, K; Boone, CW; Dasari, RR; Feld, MS
MLA Citation
Wax, A, Yang, C, Backman, V, Badizadegan, K, Boone, CW, Dasari, RR, and Feld, MS. "Cellular organization and substructure measured using angle-resolved low-coherence interferometry." Biophysical Journal 82.4 (2002): 2256-2264.
PMID
11916880
Source
scival
Published In
Biophysical Journal
Volume
82
Issue
4
Publish Date
2002
Start Page
2256
End Page
2264
DOI
10.1016/S0006-3495(02)75571-9

2π ambiguity-free optical distance measurement with subnanometer precision with a novel phase-crossing low-coherence interferometer

We report a highly accurate phase-based technique for measuring arbitrarily long optical distance with sub-nanometer precision. The method employs a Michelson interferometer with a pair of harmonically related light sources, one cw and the other low coherence. By slightly detuning (∼2 nm) the center wavelength of the low-coherence source between scans of the target sample, we can use the phase relationship between the heterodyne signals of the cw and the low-coherence light to measure the separation between reflecting interfaces with subnanometer precision. As this technique is completely free of 2π ambiguity, an issue that plagues most phase-based techniques, it can be used to measure arbitrarily long optical distances without loss of precision. We demonstrate one application of this technique, the high-precision determination of the differential refractive index. © 2002 Optical Society of America.

Authors
Yang, C; Wax, A; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Dasari, RR, and Feld, MS. "2π ambiguity-free optical distance measurement with subnanometer precision with a novel phase-crossing low-coherence interferometer." Optics Letters 27.2 (2002): 77-79.
Source
scival
Published In
Optics Letters
Volume
27
Issue
2
Publish Date
2002
Start Page
77
End Page
79

Imaging and measurement of cell structure and organization with submicron accuracy using light scattering spectroscopy

Light scattering spectroscopy (LSS) is a promising optical technique developed for quantitative characterization of tissue morphology as well as in vivo detection and diagnosis of disease such as early cancer. LSS employs a wavelength dependent component of light scattered by epithelial cells and other tissues to obtain information about subcellular structure. We present two novel modalities of LSS, LSS imaging and scattering angle sensitive LSS (a/LSS). LSS imaging provides quantitative information about the epithelial cell nuclei, such as nuclear size, degree of pleomorphism, hyperchromasia, and amount of chromatin. It allows mapping these histological properties over wide areas of epithelial lining. We show that LSS imaging can be used to detect precancerous lesions in optically accessible organs. Using a/LSS, which enables characterization of tissue components with sizes smaller than the wavelength of light, we show that the number of subcellular components with the sizes between 30 nm and few microns scales with the size according to an inverse power-law. We show that the size distribution exponent is an important parameter characterizing tissue organization, for example the balance between stochasticity and order, and has a potential to be applicable for early cancer diagnosis and characterization.

Authors
Backman, V; Gurjar, R; Perelman, LT; Gopal, V; Kalashnikov, M; Badizadegan, K; Wax, A; Georgakoudi, I; Mueller, M; Boone, CW; Itzkan, I; Dasari, RR; Feld, MS
MLA Citation
Backman, V, Gurjar, R, Perelman, LT, Gopal, V, Kalashnikov, M, Badizadegan, K, Wax, A, Georgakoudi, I, Mueller, M, Boone, CW, Itzkan, I, Dasari, RR, and Feld, MS. "Imaging and measurement of cell structure and organization with submicron accuracy using light scattering spectroscopy." Proceedings of SPIE - The International Society for Optical Engineering 4613 (2002): 101-110.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
4613
Publish Date
2002
Start Page
101
End Page
110
DOI
10.1117/12.465234

Path-length-resolved dynamic light scattering: Modeling the transition from single to diffusive scattering

Dynamic light-scattering spectroscopy is used to study Brownian motion within highly scattering samples. The fluctuations of the light field that is backscattered by a suspension of polystyrene microspheres are measured as power spectra by use of low-coherence interferometry to obtain path-length resolution. The data are modeled as the sum of contributions to the detected light weighted by a Poisson probability for the number of events that each component has experienced. By analyzing the broadening of the power spectra as a function of the path length for various sizes of particles, we determine the contribution of multiple scattering to the detected signal as a function of scattering anisotropy. © 2001 Optical Society of America.

Authors
Wax, A; Yang, C; Dasari, RR; Feld, MS
MLA Citation
Wax, A, Yang, C, Dasari, RR, and Feld, MS. "Path-length-resolved dynamic light scattering: Modeling the transition from single to diffusive scattering." Applied Optics 40.24 (2001): 4222-4227.
Source
scival
Published In
Applied Optics
Volume
40
Issue
24
Publish Date
2001
Start Page
4222
End Page
4227

Interferometric phase-based dual wavelength tomography

We describe our phase-sensitive interferometry technique implemented as phase dispersion microscopy (PDM)/optical tomography (PDOT). The technique is based on measuring the phase difference between fundamental and second harmonic low coherence light in a novel interferometer. We attain high sensitivity to subtle refractive index differences due to dispersion with a differential optical path sensitivity of 5 nm. Using PDM, we show that ballistic light in a turbid medium undergoes a phase velocity change that is dependent on scatterer size. We demonstrate that the microscopy technique performs better than a conventional phase contrast microscope in imaging dispersive and weakly scattering samples. The tomographic implementation of the technique (PDOT) can complement Optical Coherence Tomography (OCT) by providing phase information about the scanned object.

Authors
Yang, C; Wax, A; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Dasari, RR, and Feld, MS. "Interferometric phase-based dual wavelength tomography." Proceedings of SPIE - The International Society for Optical Engineering 4251 (2001): 63-70.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
4251
Publish Date
2001
Start Page
63
End Page
70
DOI
10.1117/12.427872

Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics

We report a highly sensitive means of measuring cellular dynamics with a novel interferometer that can measure motional phase changes. The system is based on a modified Michelson interferometer with a composite laser beam of 1550-nm low-coherence light and 775-nm CW light. The sample is prepared on a coverslip that is highly reflective at 775 nm. By referencing the heterodyne phase of the 1550-nm light reflected from the sample to that of the 775-nm light reflected from the coverslip, small motions in the sample are detected, and motional artifacts from vibrations in the interferometer are completely eliminated. We demonstrate that the system is sensitive to motions as small as 3.6 nm and velocities as small as 1 nm/s. Using the instrument, we study transient volume changes of a few (approximately three) cells in a monolayer immersed in weakly hypotonie and hypertonic solutions. © 2001 Optical Society of America.

Authors
Yang, C; Wax, A; Hahn, MS; Badizadegan, K; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Hahn, MS, Badizadegan, K, Dasari, RR, and Feld, MS. "Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics." Optics Letters 26.16 (2001): 1271-1273.
Source
scival
Published In
Optics Letters
Volume
26
Issue
16
Publish Date
2001
Start Page
1271
End Page
1273

Angular light scattering studies using low-coherence interferometry

A modified Michelson interferometer is used to measure path-length resolved angular distributions of light backscattered by turbid media. The path length resolution is obtained by exploiting the coherence properties of a broadband source. The angular distribution is mapped out using a simple optical system to scan the angle at which the reference field intersects the detector plane. Angular scattering distributions can be compared to Mie theory to determine the size and refractive index of spherical scatterers. Initial studies utilizing this system demonstrate the potential of low coherence interferometry for obtaining structural information using angular distributions.

Authors
Wax, A; Yang, C; Dasari, RR; Feld, MS
MLA Citation
Wax, A, Yang, C, Dasari, RR, and Feld, MS. "Angular light scattering studies using low-coherence interferometry." Proceedings of SPIE - The International Society for Optical Engineering 4251 (2001): 32-42.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
4251
Publish Date
2001
Start Page
32
End Page
42
DOI
10.1117/12.427903

Measurement of the anomalous phase velocity of ballistic light in a random medium by use of a novel interferometer

Ballistic light, i.e., radiation that propagates undeflected through a turbid medium, undergoes a small change in phase velocity and exhibits unusual dispersion because of its wave nature. We use a novel highly sensitive differential phase optical interferometer to study these previously unmeasurable phenomena. We find that ballistic propagation can be classified into three regimes based on the wavelength-to-size ratio. In the regime in which the scatterer size is comparable with the wavelength, there is an anomalous phase-velocity increase as a result of adding scatterers of higher refractive index. We also observe an anomaly in the relative phase velocity, where red light is slowed more than blue light even though the added scatterers are made of material with normal dispersion. © 2001 Optical Society of America.

Authors
Yang, C; Wax, A; Feld, MS
MLA Citation
Yang, C, Wax, A, and Feld, MS. "Measurement of the anomalous phase velocity of ballistic light in a random medium by use of a novel interferometer." Optics Letters 26.4 (2001): 235-237.
Source
scival
Published In
Optics Letters
Volume
26
Issue
4
Publish Date
2001
Start Page
235
End Page
237

Phase-referenced interferometer with subwavelength and subhertz sensitivity

A low coherence phase-referenced interferometer (PRI) that can be used to measure slow and small movements with the objective of studying subcellular dynamics was presented. The use of low coherence light in the interferometer provides depth resolution and can be used for tomographic imaging. A motional PRI achieved complete insensitivity to interferometer mechanical jitter by the simultaneous use of a cw 775-nm laser and a low coherence light source at 1550nm.

Authors
Yang, C; Wax, A; Badizadegan, K; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Badizadegan, K, Dasari, RR, and Feld, MS. "Phase-referenced interferometer with subwavelength and subhertz sensitivity." Optics and Photonics News 12.12 (2001): 36--.
Source
scival
Published In
Optics & Photonics News
Volume
12
Issue
12
Publish Date
2001
Start Page
36-

Phase-dispersion optical tomography

We report on phase-dispersion optical tomography, a new imaging technique based on phase measurements using low-coherence interferometry. The technique simultaneously probes the target with fundamental and second-harmonic light and interferometrically measures the relative phase shift of the backscattered light fields. This phase change can arise either from reflection at an interface within a sample or from bulk refraction. We show that this highly sensitive (∼5°) phase technique can complement optical coherence tomography, which measures electric field amplitude, by revealing otherwise undetectable dispersive variations in the sample. © 2001 Optical Society of America.

Authors
Yang, C; Wax, A; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Dasari, RR, and Feld, MS. "Phase-dispersion optical tomography." Optics Letters 26.10 (2001): 686-688.
Source
scival
Published In
Optics Letters
Volume
26
Issue
10
Publish Date
2001
Start Page
686
End Page
688

Multiexcitation fluorescence and reflectance spectroscopy as a real time guide to biopsy in vivo

A compact excitation-emission spectrofluorimeter system used to acquire tissue fluorescence and reflectance with fiber optic light delivery and collection is presented. Ten dye cells are pumped by a XeCl excimer laser, creating laser excitation from 308 nm to 505 nm, which is used to excite tissue fluorescence. A xenon-flash lamp is employed to obtain the reflectance spectrum of the corresponding tissue spot. Eleven fluorescence spectra and one white light diffuse reflectance spectrum are collected in vivo in 0.2 seconds and can be potentially analyzed in real time to obtain diagnostic information. The instrument can be used for early cancer detection. The measured fluorescence and reflectance spectra are used to model the intrinsic fluorescence of the tissue, which gives important insight into its biochemical composition (tryptophan, collagen, elastin, NADH, etc.) and metabolic state. Diffuse reflectance provides information about tissue morphology, in terms of the scattering and absorption coefficient. By subtracting the diffusely reflected component from the measured reflectance, light scattering spectroscopic (LSS) information due to single backscattering from epithelial cell nuclei can be obtained. LSS provides information about the size distribution of cell nuclei. The parameters give diagnostic information, which can be used to guide the physician in real time while taking biopsies of invisible tissue abnormalities.

Authors
Müller, MG; Georgakoudi, I; Wax, A; Dasari, R; Jost, C; Wallace, M; Feld, MS
MLA Citation
Müller, MG, Georgakoudi, I, Wax, A, Dasari, R, Jost, C, Wallace, M, and Feld, MS. "Multiexcitation fluorescence and reflectance spectroscopy as a real time guide to biopsy in vivo." Proceedings of SPIE - The International Society for Optical Engineering 4261 (2001): 114-121.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
4261
Publish Date
2001
Start Page
114
End Page
121
DOI
10.1117/12.424525

Measurement of angular distributions by use of low-coherence interferometry for light-scattering spectroscopy

We present a novel interferometer for measuring angular distributions of backscattered light. The new system exploits a low-coherence source in a modified Michelson interferometer to provide depth resolution, as in optical coherence tomography, but includes an imaging system that permits the angle of the reference field to be varied in the detector plane by simple translation of an optical element. We employ this system to examine the angular distribution of light scattered by polystyrene microspheres. The measured data indicate that size information can be recovered from angular-scattering distributions and that the coherence length of the source influences the applicability of Mie theory. © 2001 Optical Society of America.

Authors
Wax, A; Yang, C; Dasari, RR; Feld, MS
MLA Citation
Wax, A, Yang, C, Dasari, RR, and Feld, MS. "Measurement of angular distributions by use of low-coherence interferometry for light-scattering spectroscopy." Optics Letters 26.6 (2001): 322-324.
Source
scival
Published In
Optics Letters
Volume
26
Issue
6
Publish Date
2001
Start Page
322
End Page
324

Measuring cellular structure at submicrometer scale with light scattering spectroscopy

We present a novel instrument for imaging the angular distributions of light backscattered by biological cells and tissues. The intensities in different regions of the image are due to scatterers of different sizes. We exploit this to study scattering from particles smaller than the wavelength of light used, even when they are mixed with larger particles. We show that the scattering from subcellular structure in both normal and cancerous human cells is best fitted to inverse power-law distributions for the sizes of the scattering objects, and propose that the distribution of scattering objects may be different in normal versus cancerous cells.

Authors
Backman, V; Gopal, V; Kalashnikov, M; Badizadegan, K; Gurjar, R; Wax, A; Georgakoudi, I; Mueller, M; Boone, CW; Dasari, RR; Feld, MS
MLA Citation
Backman, V, Gopal, V, Kalashnikov, M, Badizadegan, K, Gurjar, R, Wax, A, Georgakoudi, I, Mueller, M, Boone, CW, Dasari, RR, and Feld, MS. "Measuring cellular structure at submicrometer scale with light scattering spectroscopy." IEEE Journal on Selected Topics in Quantum Electronics 7.6 (2001): 887-893.
Source
scival
Published In
IEEE Journal of Selected Topics in Quantum Electronics
Volume
7
Issue
6
Publish Date
2001
Start Page
887
End Page
893
DOI
10.1109/2944.983289

Phase dispersion optical tomography applied to study sub-cellular motions

Phase dispersion optical tomography (PDOT) technique that eliminates interferometer jitter noise was analyzed. The input light was a pair of overlapped beams of laser light at wavelength λ and 2λ. The Gelatin and water layer sandwiched between two cover slips induced an optical path change to indicate noticeable phase shifts in reflection from the bottom cover slip. The technique was applied to study onion slice and it was shown that the PDOT can be exploited for analysis of sub-cellular dynamics in biological tissues.

Authors
Yang, C; Wax, A; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Dasari, RR, and Feld, MS. "Phase dispersion optical tomography applied to study sub-cellular motions." Conference on Lasers and Electro-Optics Europe - Technical Digest (2001): 326-327.
Source
scival
Published In
Conference on Lasers and Electro-Optics Europe - Technical Digest
Publish Date
2001
Start Page
326
End Page
327

Time-resolved phase-space distributions for light backscattered from a disordered medium.

We demonstrate time-resolved measurement of optical phase-space distributions as a new probe for investigating the propagation of light in disordered media. Phase-space techniques measure the joint transverse position and momentum distribution of the scattered light, and are sensitive to the spatially varying phase and amplitude of the field. Using this method we investigate light backscattered from a random medium. The measurements indicate that the weakly localized component is a phase conjugate of the incident light field. A new model of backscatter, based on Wigner phase-space distributions, elucidates the spatial and angular behavior of the localized and unlocalized components.

Authors
Wax, A; Bali, S; Thomas, JE
MLA Citation
Wax, A, Bali, S, and Thomas, JE. "Time-resolved phase-space distributions for light backscattered from a disordered medium." Phys Rev Lett 85.1 (July 3, 2000): 66-69.
PMID
10991160
Source
pubmed
Published In
Physical Review Letters
Volume
85
Issue
1
Publish Date
2000
Start Page
66
End Page
69
DOI
10.1103/PhysRevLett.85.66

Feasibility of field-based light scattering spectroscopy

Light scattering spectroscopy (LSS) is a new technique capable of accurately measuring the features of nuclei and other cellular organelles in situ. We present the considerations required to implement and interpret field-based detection in LSS, where the scattered electric field is detected interferometrically, and demonstrate that the technique is experimentally feasible. A theoretical formalism for modeling field-based LSS signals based on Mie scattering is presented. Phase-front uniformity is shown to play an important and novel role. Results of heterodyne experiments with polystyrene microspheres that localize LSS signals to a region about 30 μm in axial extent are reported. In addition, differences between field-based LSS and the earlier intensity-based LSS are discussed.

Authors
Yang, C; Perelman, LT; Wax, A; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Perelman, LT, Wax, A, Dasari, RR, and Feld, MS. "Feasibility of field-based light scattering spectroscopy." Journal of Biomedical Optics 5.2 (2000): 138-143.
PMID
10938777
Source
scival
Published In
Journal of Biomedical Optics
Volume
5
Issue
2
Publish Date
2000
Start Page
138
End Page
143
DOI
10.1117/1.429980

Interferometric phase-dispersion microscopy

We describe a new scanning microscopy technique, phase-dispersion microscopy (PDM). The technique is based on measuring the phase difference between the fundamental and the second-harmonic light in a novel interferometer. PDM is highly sensitive to subtle refractive-index differences that are due to dispersion (differential optical path sensitivity, 5 nm). We apply PDM to measure minute amounts of DNA in solution and to study biological tissue sections. We demonstrate that PDM performs better than conventional phase-contrast microscopy in imaging dispersive and weakly scattering samples. © 2000 Optical Society of America.

Authors
Yang, C; Wax, A; Georgakoudi, I; Hanlon, EB; Badizadegan, K; Dasari, RR; Feld, MS
MLA Citation
Yang, C, Wax, A, Georgakoudi, I, Hanlon, EB, Badizadegan, K, Dasari, RR, and Feld, MS. "Interferometric phase-dispersion microscopy." Optics Letters 25.20 (2000): 1526-1528.
Source
scival
Published In
Optics Letters
Volume
25
Issue
20
Publish Date
2000
Start Page
1526
End Page
1528

Wigner phase space distributions and coherence tomography

Authors
Thomas, JE; Reil, F; Lee, KF; Wax, A; Bali, S
MLA Citation
Thomas, JE, Reil, F, Lee, KF, Wax, A, and Bali, S. "Wigner phase space distributions and coherence tomography." OPTICAL PULSE AND BEAM PROPAGATION II 3927 (2000): 147-155.
Source
wos-lite
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
3927
Publish Date
2000
Start Page
147
End Page
155
DOI
10.1117/12.382047

Time-resolved optical phase space distributions for coherent backscatter

We explore enhanced backscatter from a random medium using time-resolved optical phase space measurement, i.e. measurement of joint position and momentum (x, p) distributions of the light field as a function of propagation time in the medium. Enhanced backscatter is a coherent effect and is not predicted by radiative transport theories. By using a low-coherence source in a heterodyne detection scheme, we observe enhanced backscattering resolved by path length in the random medium, effectively providing timing resolution. Such time-resolved studies are important for exploring the evolution of optical coherence as a function of penetration depth in the random medium. Optical phase space methods provide a visual as well as quantitative method of characterizing the spatial coherence properties and wavefront curvature of the input and scattered fields. These techniques may provide new venues for using optical coherence in medical imaging.

Authors
Wax, A; Reil, F; Lee, KF; Bali, S; Thomas, JE
MLA Citation
Wax, A, Reil, F, Lee, KF, Bali, S, and Thomas, JE. "Time-resolved optical phase space distributions for coherent backscatter." Proceedings of SPIE - The International Society for Optical Engineering 4001 (2000): 130-134.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
4001
Publish Date
2000
Start Page
130
End Page
134

Wigner phase space distributions and coherence tomography

We demonstrate the measurement of path-length-resolved optical phase space distributions as a new framework for exploring the evolution of optical coherence in a turbid medium. This method measures joint transverse position and momentum (i.e., angle) distributions of the optical field, resolved by optical path length in the medium. The measured distributions are related to the Wigner phase space distribution function of the optical field, and can provide complete characterization of the optical coherence in multiple scattering media. Optical phase space distributions are obtained as contour plots which enable a visual as well as quantitative method of characterizing the spatial coherence properties and wavefront curvature of the input and scattered fields. By using a broad-band source in a heterodyne detection scheme, we observe transmission and backscatter resolved by path length in the random medium, effectively providing time resolution. New two-window heterodyne detection methods permit independent control of position and momentum resolution with a variance product that surpasses the uncertainty limit associated with Fourier transform pairs. Hence, high position and angular resolution can be simultaneously achieved. These techniques may provide new venues for using optical coherence in medical imaging.

Authors
Thomas, JE; Reil, F; Lee, KF; Wax, A; Bali, S
MLA Citation
Thomas, JE, Reil, F, Lee, KF, Wax, A, and Bali, S. "Wigner phase space distributions and coherence tomography." Proceedings of SPIE - The International Society for Optical Engineering 3914 (2000): 363-371.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
3914
Publish Date
2000
Start Page
363
End Page
371

Optical phase-space distributions for low-coherence light

Using a novel heterodyne technique, we measure optical phase-space distributions in momentum and position for low-coherence light. Quantitative information is obtained simultaneously about the longitudinal and the transverse coherence properties as well as the wave-front curvature of the light field. This method can be used to monitor these optical parameters directly for signal fields scattered from samples of interest, for tomographic imaging. © 1999 Optical Society of America.

Authors
Wax, A; Bali, S; Thomas, JE
MLA Citation
Wax, A, Bali, S, and Thomas, JE. "Optical phase-space distributions for low-coherence light." Optics Letters 24.17 (1999): 1188-1190.
PMID
18073979
Source
scival
Published In
Optics Letters
Volume
24
Issue
17
Publish Date
1999
Start Page
1188
End Page
1190

Heterodyne measurement of Wigner distributions for classical optical fields

We demonstrate a two-window heterodyne method for measuring the x-p cross correlation, 〈E*(x)E(p)〉, of an optical field E for transverse position x and transverse momentum p. This scheme permits independent control of the x and p resolution. A simple linear transform of the x-p correlation function yields the Wigner phase-space distribution. This technique is useful for both coherent and low-coherence light sources and may permit new biological imaging techniques based on transverse coherence measurement with time gating. We point out an interesting analogy between x-p correlation measurements for classical-wave and quantum fields. © 1999 Optical Society of America.

Authors
Lee, KF; Reil, F; Bali, S; Wax, A; Thomas, JE
MLA Citation
Lee, KF, Reil, F, Bali, S, Wax, A, and Thomas, JE. "Heterodyne measurement of Wigner distributions for classical optical fields." Optics Letters 24.19 (1999): 1370-1372.
PMID
18079807
Source
scival
Published In
Optics Letters
Volume
24
Issue
19
Publish Date
1999
Start Page
1370
End Page
1372

Measurement of smoothed Wigner phase space distributions for coherence tomography

We use heterodyne detection to characterize the Wigner phase space distribution W (x, p) of an optical field in position x and momentum p. This method yields smoothed Wigner phase space distributions directly as contour plots and can be applied with either coherent or low coherence light sources. The measured phase space distributions are used to characterize the light sources and to study light propagation in multiple scattering media. These techniques may find important applications in understanding and enhancing images obtained in coherence tomography.

Authors
Wax, A; Thomas, JE
MLA Citation
Wax, A, and Thomas, JE. "Measurement of smoothed Wigner phase space distributions for coherence tomography." Proceedings of SPIE - The International Society for Optical Engineering 3726 (1999): 494-501.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
3726
Publish Date
1999
Start Page
494
End Page
501

Characterizing the coherence of broadband sources using optical phase space contours

Advances in optical coherence tomography (OCT) rely on the availability of broadband light that is spatially coherent. We present a technique to characterize coherence properties of broadband light using optical phase-space contours in transverse momentum and position. We demonstrate that these contour plots can be directly measured by a simple heterodyne imaging scheme possessing high dynamic range (130 dB) and 0.1 fW sensitivity (for mW input beams). These phase space distributions are shown to yield quantitative information on the longitudinal and transverse coherence and the wavefront curvature of the light beam. We apply this technique to characterize the light emitted by a novel high-power extended-bandwidth superluminescent diode (SLD) recently developed at the David Sarnoff Research Center. Its performance is compared to that of standard commercially available SLDs.

Authors
Wax, A; Bali, S; Alphonse, GA; Thomas, JE
MLA Citation
Wax, A, Bali, S, Alphonse, GA, and Thomas, JE. "Characterizing the coherence of broadband sources using optical phase space contours." Journal of Biomedical Optics 4.4 (1999): 482-489.
PMID
23014622
Source
scival
Published In
Journal of Biomedical Optics
Volume
4
Issue
4
Publish Date
1999
Start Page
482
End Page
489
DOI
10.1117/1.429961

Measurement of smoothed Wigner phase space distributions for coherence tomography

We use heterodyne detection to characterize the Wigner phase space distribution W(x, p) of an optical field in position x and momentum p. This method yields smoothed Wigner phase space distributions directly as contour plots and can be applied with either coherent or low coherence light sources. The measured phase space distributions are used to characterize the light sources and to study light propagation in multiple scattering media. These techniques may find important applications in understanding and enhancing images obtained in coherence tomography.

Authors
Wax, A; Thomas, JE
MLA Citation
Wax, A, and Thomas, JE. "Measurement of smoothed Wigner phase space distributions for coherence tomography." Proceedings of SPIE - The International Society for Optical Engineering 3598 (1999): 2-9.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
3598
Publish Date
1999
Start Page
2
End Page
9

Measurement of smoothed Wigner phase-space distributions for small-angle scattering in a turbid medium.

We study Wigner phase-space distributions W (x, p) in position (x) and momentum (p) for light undergoing multiple small-angle scattering in a turbid medium. Smoothed Wigner phase-space distributions are measured by using a heterodyne technique that achieves position and momentum resolution determined by the width and the diffraction angle of the local oscillator beam. The sample consists of 5.7-micron-radius polystyrene spheres suspended in a water-glycerol mixture. The momentum distribution of the transmitted light is found to contain a ballistic peak, a narrow diffractive pedestal, and a broad background. The narrow diffractive pedestal is found to decay more slowly than the ballistic peak as the concentration of scatterers is increased. The data are in excellent agreement with a simple theoretical model that explains the behavior of the narrow pedestal by including multiple diffractive scattering and treating large-angle scattering as a loss.

Authors
Wax, A; Thomas, JE
MLA Citation
Wax, A, and Thomas, JE. "Measurement of smoothed Wigner phase-space distributions for small-angle scattering in a turbid medium." J Opt Soc Am A Opt Image Sci Vis 15.7 (July 1998): 1896-1908.
PMID
9656479
Source
pubmed
Published In
Journal of the Optical Society of America A
Volume
15
Issue
7
Publish Date
1998
Start Page
1896
End Page
1908

Wigner phase space distributions and optical coherence in turbid media

Smoothed Wigner phase space contours can be directly measured using a simple heterodyne detection-based optical system employing a He-Ne laser beam split into a 1 mW local oscillator and a 1 mW signal beam, and a spectrum analyzer for real time mean square beat amplitude measurement. Measured Wigner phase space distribution for 10 micron spheres in a water-glycerol mixture reveals a narrow diffraction component and a broad classical scattering with approximately equal cross sections. The momentum distribution of the scattered light agrees well with the Mie solution at low concentrations, but shows a narrow pedestal near the ballistic peak as well as a broader diffuse scattering contribution which disappears to the background as concentration increases.

Authors
Wax, A; Thomas, JE
MLA Citation
Wax, A, and Thomas, JE. "Wigner phase space distributions and optical coherence in turbid media." Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS 11 (1997): 41--.
Source
scival
Published In
Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS
Volume
11
Publish Date
1997
Start Page
41-

Optical heterodyne imaging and Wigner phase space distributions

We demonstrate that optical heterodyne imaging directly measures smoothed Wigner phase space distributions. This method may be broadly applicable to fundamental studies of light propagation and tomographic imaging. Basic physical properties of Wigner distributions are illustrated by experimental measurements. © 1996 Optical Society of America.

Authors
Wax, A; Thomas, JE
MLA Citation
Wax, A, and Thomas, JE. "Optical heterodyne imaging and Wigner phase space distributions." Optics Letters 21.18 (1996): 1427-1429.
PMID
19881680
Source
scival
Published In
Optics Letters
Volume
21
Issue
18
Publish Date
1996
Start Page
1427
End Page
1429
Show More

Research Areas:

  • Anemia, Sickle Cell
  • Biomechanics
  • Biomedical Engineering
  • Biophysics
  • Biopsy
  • Biosensing Techniques
  • Burns
  • Carcinogens
  • Cartilage, Articular
  • Cell Differentiation
  • Cell Nucleus
  • Cell Nucleus Size
  • Cell Size
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Chromatin
  • Computer Simulation
  • Diagnostic Imaging
  • Disease Models, Animal
  • Early Detection of Cancer
  • Emulsions
  • Epithelial Cells
  • Equipment Design
  • Erythrocytes
  • Erythrocytes, Abnormal
  • Esophageal Neoplasms
  • Esophagus
  • Fiber Optic Technology
  • Fourier Analysis
  • Fractals
  • Gels
  • Image Interpretation, Computer-Assisted
  • Interferometry
  • Intestines
  • Light
  • Metal Nanoparticles
  • Mice
  • Microscopy
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Microscopy, Interference
  • Microspheres
  • Molecular Imaging
  • Mucous Membrane
  • Muscle, Skeletal
  • Nanoparticles
  • Nanotechnology
  • Neoplasms, Experimental
  • Nonlinear Dynamics
  • Optical Imaging
  • Optical Phenomena
  • Optical coherence tomography
  • Particle Size
  • Phantoms, Imaging
  • Phospholipids
  • Photons
  • Polymers
  • Precancerous Conditions
  • Receptor, Epidermal Growth Factor
  • Receptors, Cell Surface
  • Refractometry
  • Scattering, Radiation
  • Signal Processing, Computer-Assisted
  • Skin
  • Spectrum Analysis
  • Staining and Labeling
  • Stem Cells
  • Surface Plasmon Resonance
  • Surface Properties
  • Tissue Culture Techniques
  • Tomography, Optical Coherence
  • Tumor Cells, Cultured
  • Vaginal Creams, Foams, and Jellies