You are here

Yao, Junjie

Overview:

Our mission at PI-Lab is to develop state-of-the-art photoacoustic tomography (PAT) technologies and translate PAT advances into diagnostic and therapeutic applications, especially in functional brain imaging and early cancer theranostics. PAT is the most sensitive modality for imaging rich optical absorption contrast over a wide range of spatial scales at high speed, and is one of the fastest growing biomedical imaging technologies. Using numerous endogenous and exogenous contrasts, PAT can provide high-resolution images at scales covering organelles, cells, tissues, organs, small-animal organisms, up to humans, and can reveal tissue’s anatomical, functional, metabolic, and even histologic properties, with molecular and neuronal specificity.


At PI-Lab, we develop PAT technologies with novel and advanced imaging performance, in terms of spatial resolutions, imaging speed, penetration depth, detection sensitivity, and functionality. We are interested with all aspects of PAT technology innovations, including efficient light illumination, high-sensitivity ultrasonic detection, super-resolution PAT, high-speed imaging acquisition, novel PA genetic contrast, and precise image reconstruction. On top of the technological advancements, we are devoted to serve the broad life science and medical communities with matching PAT systems for various research and clinical needs. With its unique contrast mechanism, high scalability, and inherent functional and molecular imaging capabilities, PAT is well suited for a variety of pre-clinical applications, especially for studying tumor angiogenesis, cancer hypoxia, and brain disorders; it is also a promising tool for clinical applications in procedures such as cancer screening, melanoma staging, and endoscopic examination.

Positions:

Assistant Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2012

Ph.D. — Washington University

News:

Awards:

OSA/Quantel Bright Idea Competition (Finalist). Optical Society of America.

Type
International
Awarded By
Optical Society of America
Date
May 01, 2017

Seno Medical Best Paper Award. SPIE conference Photons Plus Ultrasound 2016: Imaging and Sensing.

Type
International
Awarded By
SPIE conference Photons Plus Ultrasound 2016: Imaging and Sensing
Date
February 01, 2016

Thousand Talents Program for Distinguished Chinese Young Scholar. Central Coordination Committee of China .

Type
National
Awarded By
Central Coordination Committee of China
Date
January 01, 2016

Seno Medical Best Paper Award. SPIE conference Photons Plus Ultrasound 2015: Imaging and Sensing .

Type
International
Awarded By
SPIE conference Photons Plus Ultrasound 2015: Imaging and Sensing
Date
February 01, 2015

Seno Medical Best Paper Award. SPIE conference Photons Plus Ultrasound 2013: Imaging and Sensing .

Type
International
Awarded By
SPIE conference Photons Plus Ultrasound 2013: Imaging and Sensing
Date
February 01, 2013

Chinese Government Award for Outstanding Self-financed Students Aboard. The Education Ministry of China.

Type
National
Awarded By
The Education Ministry of China
Date
December 01, 2012

Best Master Dissertation Award. Tsinghua University.

Type
School
Awarded By
Tsinghua University
Date
July 01, 2008

Comprehensive Student Fellowship. Tsinghua University.

Type
School
Awarded By
Tsinghua University
Date
January 01, 2008

KangShien Outstanding Graduate Fellowship. Tsinghua University.

Type
University
Awarded By
Tsinghua University
Date
July 01, 2006

CyrusTang Fellowship (2002-2006). Tsinghua University.

Type
University
Awarded By
Tsinghua University
Date
September 01, 2002

Publications:

Correcting the limited view in optical-resolution photoacoustic microscopy.

Optical-resolution photoacoustic microscopy (OR-PAM) has proven useful for anatomical and functional imaging with high spatial resolutions. However, the coherent signal generation and the desired reflection-mode detection in OR-PAM can result in a limited detectability of features aligned with the acoustic axis (i.e., vertical structures). Here, we investigated the limited-view phenomenon in OR-PAM by simulating the generation and propagation of the acoustic pressure waves and determined the key optical parameters affecting the visibility of vertical structures. Proof-of-concept numerical experiments were performed with different illumination angles, optical foci, and numerical apertures (NA) of the objective lens. The results collectively show that an NA of 0.3 can readily improve the visibility of vertical structures in a typical reflection-mode OR-PAM system. This conclusion was confirmed by numerical simulations on the cortical blood vessels in a mouse brain, and by experiments in a suture-cross phantom and in a mouse brain in vivo.

Authors
Liu, W; Zhou, Y; Wang, M; Li, L; Vienneau, E; Chen, R; Luo, J; Xu, C; Zhou, Q; Wang, LV; Yao, J
MLA Citation
Liu, W, Zhou, Y, Wang, M, Li, L, Vienneau, E, Chen, R, Luo, J, Xu, C, Zhou, Q, Wang, LV, and Yao, J. "Correcting the limited view in optical-resolution photoacoustic microscopy." Journal of biophotonics (October 3, 2017).
PMID
28971578
Source
epmc
Published In
Journal of biophotonics
Publish Date
2017
DOI
10.1002/jbio.201700196

Photoacoustic thermal flowmetry with a single light source.

We report a photoacoustic thermal flowmetry based on optical-resolution photoacoustic microscopy (OR-PAM) using a single laser source for both thermal tagging and photoacoustic excitation. When an optically absorbing medium is flowing across the optical focal zone of OR-PAM, a small volume of the medium within the optical focus is repeatedly illuminated and heated by a train of laser pulses with a high repetition rate. The average temperature of the heated volume at each laser pulse is indicated by the photoacoustic signal excited by the same laser pulse due to the well-established linear relationship between the Grueneisen coefficient and the local temperature. The thermal dynamics of the heated medium volume, which are closely related to the flow speed, can therefore be measured from the time course of the detected photoacoustic signals. Here, we have developed a lumped mathematical model to describe the time course of the photoacoustic signals as a function of the medium's flow speed. We conclude that the rising time constant of the photoacoustic signals is linearly dependent on the flow speed. Thus, the flow speed can be quantified by fitting the measured photoacoustic signals using the derived mathematical model. We first performed proof-of-concept experiments using defibrinated bovine blood flowing in a plastic tube. The experiment results have demonstrated that the proposed method has high accuracy (∼±6%) and a wide range of measurable flow speeds. We further validated the method by measuring the blood flow speeds of the microvasculature in a mouse ear in vivo.

Authors
Liu, W; Lan, B; Hu, L; Chen, R; Zhou, Q; Yao, J
MLA Citation
Liu, W, Lan, B, Hu, L, Chen, R, Zhou, Q, and Yao, J. "Photoacoustic thermal flowmetry with a single light source." Journal of biomedical optics 22.9 (September 2017): 1-6.
PMID
28875623
Source
epmc
Published In
Journal of Biomedical Optics
Volume
22
Issue
9
Publish Date
2017
Start Page
1
End Page
6
DOI
10.1117/1.jbo.22.9.096001

Photoacoustic imaging using genetically encoded reporters: a review.

Genetically encoded contrast in photoacoustic imaging (PAI) is complementary to the intrinsic contrast provided by endogenous absorbing chromophores such as hemoglobin. The use of reporter genes expressing absorbing proteins opens the possibility of visualizing dynamic cellular and molecular processes. This is an enticing prospect but brings with it challenges and limitations associated with generating and detecting different types of reporters. The purpose of this review is to compare existing PAI reporters and signal detection strategies, thereby offering a practical guide, particularly for the nonbiologist, to choosing the most appropriate reporter for maximum sensitivity in the biological and technological system of interest.

Authors
Brunker, J; Yao, J; Laufer, J; Bohndiek, SE
MLA Citation
Brunker, J, Yao, J, Laufer, J, and Bohndiek, SE. "Photoacoustic imaging using genetically encoded reporters: a review." Journal of biomedical optics 22.7 (July 2017).
PMID
28717818
Source
epmc
Published In
Journal of Biomedical Optics
Volume
22
Issue
7
Publish Date
2017
DOI
10.1117/1.jbo.22.7.070901

When pressure meets light: detecting the photoacoustic effect at the origin

Authors
Yao, J
MLA Citation
Yao, J. "When pressure meets light: detecting the photoacoustic effect at the origin." Light: Science & Applications 6.6 (June 2, 2017): e17062-e17062.
Source
crossref
Published In
Light: Science and Applications
Volume
6
Issue
6
Publish Date
2017
Start Page
e17062
End Page
e17062
DOI
10.1038/lsa.2017.62

High-speed photoacoustic microscopy of mouse cortical microhemodynamics.

We applied high-speed photoacoustic microscopy (PAM) for both cortical microenvironment studies and dynamic brain studies, with micrometer-level optical resolution and a millisecond-level cross-sectional imaging speed over a millimeter-level field of view. We monitored blood flow redistribution in mini-stroke mouse models and cerebral autoregulation induced by a vasoactive agent. Our results collectively suggest that high-speed PAM is a promising tool for understanding dynamic neurophysiological phenomena, complementing conventional imaging modalities.

Authors
Lin, L; Yao, J; Zhang, R; Chen, C-C; Huang, C-H; Li, Y; Wang, L; Chapman, W; Zou, J; Wang, LV
MLA Citation
Lin, L, Yao, J, Zhang, R, Chen, C-C, Huang, C-H, Li, Y, Wang, L, Chapman, W, Zou, J, and Wang, LV. "High-speed photoacoustic microscopy of mouse cortical microhemodynamics." Journal of biophotonics 10.6-7 (June 2017): 792-798.
PMID
28009098
Source
epmc
Published In
Journal of biophotonics
Volume
10
Issue
6-7
Publish Date
2017
Start Page
792
End Page
798
DOI
10.1002/jbio.201600236

Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution

Authors
Li, L; Zhu, L; Ma, C; Lin, L; Yao, J; Wang, L; Maslov, K; Zhang, R; Chen, W; Shi, J; Wang, LV
MLA Citation
Li, L, Zhu, L, Ma, C, Lin, L, Yao, J, Wang, L, Maslov, K, Zhang, R, Chen, W, Shi, J, and Wang, LV. "Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution." Nature Biomedical Engineering 1.5 (May 10, 2017): 0071-0071.
Source
crossref
Volume
1
Issue
5
Publish Date
2017
Start Page
0071
End Page
0071
DOI
10.1038/s41551-017-0071

Handheld optical-resolution photoacoustic microscopy.

Optical-resolution photoacoustic microscopy (OR-PAM) offers label-free

Authors
Lin, L; Zhang, P; Xu, S; Shi, J; Li, L; Yao, J; Wang, L; Zou, J; Wang, LV
MLA Citation
Lin, L, Zhang, P, Xu, S, Shi, J, Li, L, Yao, J, Wang, L, Zou, J, and Wang, LV. "Handheld optical-resolution photoacoustic microscopy." Journal of biomedical optics 22.4 (April 2017): 41002-.
PMID
27775746
Source
epmc
Published In
Journal of Biomedical Optics
Volume
22
Issue
4
Publish Date
2017
Start Page
41002
DOI
10.1117/1.jbo.22.4.041002

Direct measurement of hypoxia in a xenograft multiple myeloma model by optical-resolution photoacoustic microscopy.

Using photoacoustic microscopy (PAM), we evaluated non-invasively oxygenation and vascularization in vivo due to multiple myeloma (MM) progression. Mice injected with MM.1S-GFP were monitored with a fluorescence microscope for tumor progression. In vivo PAM of the cerebral bone marrow quantified the total oxygen saturation (sO2). At 28 days after the MM cell injection, the total sO2 had decreased by half in the developing tumor regions, while in the non-tumor regions it had decreased by 20% compared with the value at one day post MM injection. The blood vessel density was reduced by 35% in the developing tumor regions, while in the non-tumor regions it was reduced by 8% compared with the value at one day post MM injection. Hence, PAM corroborated the development of hypoxia due to MM progression and demonstrated decreased vascularization surrounding the tumor areas.

Authors
Imai, T; Muz, B; Yeh, C-H; Yao, J; Zhang, R; Azab, AK; Wang, L
MLA Citation
Imai, T, Muz, B, Yeh, C-H, Yao, J, Zhang, R, Azab, AK, and Wang, L. "Direct measurement of hypoxia in a xenograft multiple myeloma model by optical-resolution photoacoustic microscopy." Cancer biology & therapy 18.2 (February 2017): 101-105.
PMID
28045569
Source
epmc
Published In
Cancer Biology and Therapy
Volume
18
Issue
2
Publish Date
2017
Start Page
101
End Page
105
DOI
10.1080/15384047.2016.1276137

Real-time photoacoustic flow cytography and photothermolysis of single circulating melanoma cells in vivo

© 2017 SPIE. Metastasis is responsible for as many as 90% of cancer-related deaths, and the deadliest skin cancer, melanoma, has a high propensity for metastasis. Since hematogenous spread of circulating tumor cells (CTCs) is cancer's main route of metastasis, detecting and destroying CTCs can impede metastasis and improve patients' prognoses. Extensive studies employing exogenous agents to detect tumor-specific biomarkers and guide therapeutics to CTCs have achieved promising results, but biosafety remains a critical concern. Taking another approach, physical detection and destruction of CTCs is a safer way to evaluate and reduce metastasis risks. Melanoma cells strongly express melanosomes, providing a striking absorption contrast with the blood background in the red to near-infrared spectrum. Exploiting this intrinsic optical absorption contrast of circulating melanoma cells, we coupled dual-wavelength photoacoustic flow cytography with a nanosecond-pulsed laser killing mechanism that specifically targets melanoma CTCs. We have successfully achieved in vivo label-free imaging of rare single CTCs and CTC clusters in mice. Further, the photoacoustic signal from a CTC immediately hardware-triggers a lethal pinpoint laser irradiation that lyses it on the spot in a thermally confined manner. Our technology can facilitate early inhibition of metastasis by clearing circulating tumor cells from vasculature.

Authors
He, Y; Wang, L; Shi, J; Yao, J; Li, L; Zhang, R; Huang, CH; Zou, J; Wang, LV
MLA Citation
He, Y, Wang, L, Shi, J, Yao, J, Li, L, Zhang, R, Huang, CH, Zou, J, and Wang, LV. "Real-time photoacoustic flow cytography and photothermolysis of single circulating melanoma cells in vivo." January 1, 2017.
Source
scopus
Published In
Proceedings of SPIE
Volume
10064
Publish Date
2017
DOI
10.1117/12.2255068

Imaging small animal whole-body dynamics by single-impulse panoramic photoacoustic computed tomography

© 2017 SPIE. Small animal whole-body imaging, providing physiological, pathological, and phenotypical insights into biological processes, is indispensable in preclinical research. With high spatiotemporal resolution and functional contrast, small animal imaging can visualize biological dynamics in vivo at whole-body scale, which can advance both fundamental biology and translational medicine. However, current non-optical imaging techniques lack either spatiotemporal resolution or functional contrasts, and pure optical imaging suffers from either shallow penetration (up to ∼1 mm) or a poor resolution-to-depth ratio (∼1/3). Here, we present a standalone system, termed single-impulse panoramic photoacoustic computed tomography (SIP-PACT), which overcomes all the above limitations. Our technology, with unprecedented performance, is envisioned to complement existing modalities for imaging entire small animals. As an optical imaging modality, SIP-PACT captures the high molecular contrast of endogenous substances such as hemoglobin, melanin, and lipid, as well as exogenous biomarkers, at the whole animal scale with full-view fidelity. Unlike other optical imaging methods, SIP-PACT sees through ∼5 cm of tissue in vivo, and acquires cross-sectional images with an in-plane resolution of ∼100 μm. Such capabilities allow us to image, for the first time, mouse wholebody dynamics in real time with clear sub-organ anatomical and functional details and without motion artifacts. SIPPACT can capture transients of whole-body oxygen saturation and pulse wave propagation in vivo without labeling. In sum, we expect widespread applications of SIP-PACT as a whole-body imaging tool for small animals in fundamental biology, pharmacology, pathology, oncology, and other areas.

Authors
Li, L; Zhu, L; Ma, C; Lin, L; Yao, J; Wang, L; Maslov, K; Zhang, R; Chen, W; Shi, J; Wang, LV
MLA Citation
Li, L, Zhu, L, Ma, C, Lin, L, Yao, J, Wang, L, Maslov, K, Zhang, R, Chen, W, Shi, J, and Wang, LV. "Imaging small animal whole-body dynamics by single-impulse panoramic photoacoustic computed tomography." January 1, 2017.
Source
scopus
Published In
Proceedings of SPIE
Volume
10064
Publish Date
2017
DOI
10.1117/12.2251593

Wide-field fast-scanning photoacoustic microscopy of brain functions in action

© 2017 OSA. We have developed fast functional photoacoustic microscopy for 3D highresolution high-speed imaging of the mouse brain. In particular, a novel single-wavelength pulsewidth- based method can image blood oxygenation with capillary-level resolution at 100 kHz frame rate.

Authors
Yao, J; Zou, J; Wang, LV
MLA Citation
Yao, J, Zou, J, and Wang, LV. "Wide-field fast-scanning photoacoustic microscopy of brain functions in action." January 1, 2017.
Source
scopus
Published In
Optics InfoBase Conference Papers
Volume
Part F43-CLEO_AT 2017
Publish Date
2017
DOI
10.1364/CLEO_AT.2017.ATu1B.5

In vivo label-free photoacoustic flow cytography and on-the-spot laser killing of single circulating melanoma cells.

Metastasis causes as many as 90% of cancer-related deaths, especially for the deadliest skin cancer, melanoma. Since hematogenous dissemination of circulating tumor cells is the major route of metastasis, detection and destruction of circulating tumor cells are vital for impeding metastasis and improving patient prognosis. Exploiting the exquisite intrinsic optical absorption contrast of circulating melanoma cells, we developed dual-wavelength photoacoustic flow cytography coupled with a nanosecond-pulsed melanoma-specific laser therapy mechanism. We have successfully achieved in vivo label-free imaging of rare single circulating melanoma cells in both arteries and veins of mice. Further, the photoacoustic signal from a circulating melanoma cell immediately hardware-triggers a lethal pinpoint laser irradiation to kill it on the spot in a thermally confined manner without causing collateral damage. A pseudo-therapy study including both in vivo and in vitro experiments demonstrated the performance and the potential clinical value of our method, which can facilitate early treatment of metastasis by clearing circulating tumor cells from vasculature.

Authors
He, Y; Wang, L; Shi, J; Yao, J; Li, L; Zhang, R; Huang, C-H; Zou, J; Wang, LV
MLA Citation
He, Y, Wang, L, Shi, J, Yao, J, Li, L, Zhang, R, Huang, C-H, Zou, J, and Wang, LV. "In vivo label-free photoacoustic flow cytography and on-the-spot laser killing of single circulating melanoma cells." Scientific reports 6 (December 21, 2016): 39616-.
PMID
28000788
Source
epmc
Published In
Scientific Reports
Volume
6
Publish Date
2016
Start Page
39616
DOI
10.1038/srep39616

A practical guide to photoacoustic tomography in the life sciences.

The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs.

Authors
Wang, LV; Yao, J
MLA Citation
Wang, LV, and Yao, J. "A practical guide to photoacoustic tomography in the life sciences." Nature methods 13.8 (July 2016): 627-638. (Review)
Website
http://hdl.handle.net/10161/12770
PMID
27467726
Source
epmc
Published In
Nature Methods
Volume
13
Issue
8
Publish Date
2016
Start Page
627
End Page
638
DOI
10.1038/nmeth.3925

Tutorial on photoacoustic tomography.

Photoacoustic tomography (PAT) has become one of the fastest growing fields in biomedical optics. Unlike pure optical imaging, such as confocal microscopy and two-photon microscopy, PAT employs acoustic detection to image optical absorption contrast with high-resolution deep into scattering tissue. So far, PAT has been widely used for multiscale anatomical, functional, and molecular imaging of biological tissues. We focus on PAT’s basic principles, major implementations, imaging contrasts, and recent applications.

Authors
Zhou, Y; Yao, J; Wang, LV
MLA Citation
Zhou, Y, Yao, J, and Wang, LV. "Tutorial on photoacoustic tomography." Journal of biomedical optics 21.6 (June 2016): 61007-. (Review)
PMID
27086868
Source
epmc
Published In
Journal of Biomedical Optics
Volume
21
Issue
6
Publish Date
2016
Start Page
61007
DOI
10.1117/1.jbo.21.6.061007

In vivo photoacoustic tomography of myoglobin oxygen saturation.

Myoglobin is an essential oxygen-binding hemoprotein in skeletal and cardiac muscles that buffers intracellular oxygen (O2) concentration in response to hypoxia or elevated muscle activities. We present a method that uses photoacoustic computed tomography to measure the distribution of myoglobin in tissue and the oxygen saturation of myoglobin (sO2-Mb ). From photoacoustic measurements of mice in different oxygenation states, we performed calibration-free quantification of the sO2-Mb change in the backbone muscle in vivo.

Authors
Lin, L; Yao, J; Li, L; Wang, LV
MLA Citation
Lin, L, Yao, J, Li, L, and Wang, LV. "In vivo photoacoustic tomography of myoglobin oxygen saturation." Journal of Biomedical Optics 21.6 (June 2016): 61002-.
PMID
26719943
Source
epmc
Published In
Journal of Biomedical Optics
Volume
21
Issue
6
Publish Date
2016
Start Page
61002
DOI
10.1117/1.jbo.21.6.061002

Photoacoustic elastography.

Elastography can noninvasively map the elasticity distribution in biological tissue, which can potentially be used to reveal disease conditions. In this Letter, we have demonstrated photoacoustic elastography by using a linear-array photoacoustic computed tomography system. The feasibility of photoacoustic elastography was first demonstrated by imaging the strains of single-layer and bilayer gelatin phantoms with various stiffness values. The measured strains agreed well with theoretical values, with an average error of less than 5.2%. Next, in vivo photoacoustic elastography was demonstrated on a mouse leg, where the fat and muscle distribution was mapped based on the elasticity contrast. We confirmed the photoacoustic elastography results by ultrasound elastography performed simultaneously.

Authors
Hai, P; Yao, J; Li, G; Li, C; Wang, LV
MLA Citation
Hai, P, Yao, J, Li, G, Li, C, and Wang, LV. "Photoacoustic elastography." Optics letters 41.4 (February 2016): 725-728.
PMID
26872173
Source
epmc
Published In
Optics Letters
Volume
41
Issue
4
Publish Date
2016
Start Page
725
End Page
728
DOI
10.1364/ol.41.000725

Reversibly switchable photoacoustic tomography using a genetically encoded near-infrared phytochrome

© 2016 SPIE. Optical imaging of genetically encoded probes has revolutionized biomedical studies by providing valuable information about targeted biological processes. Here, we report a novel imaging technique, termed reversibly switchable photoacoustic tomography (RS-PAT), which exhibits large penetration depth, high detection sensitivity, and super-resolution. RS-PAT combines advanced photoacoustic imaging techniques with, for the first time, a nonfluorescent photoswitchable bacterial phytochrome. This bacterial phytochrome is the most near-infrared shifted genetically encoded probe reported so far. Moreover, this bacterial phytochrome is reversibly photoconvertible between its far-red and near-infrared light absorption states. Taking maximum advantage of the powerful imaging capability of PAT and the unique photochemical properties of the phytochrome, RS-PAT has broken through both the optical diffusion limit for deep-tissue imaging and the optical diffraction limit for super-resolution photoacoustic microscopy. Specifically, with RS-PAT we have achieved an unprecedented detection sensitivity of ∼2 μM, or as few as ∼20 tumor cells, at a centimeter depth. Such high sensitivity is fully demonstrated in our study by monitoring tumor growth and metastasis at whole-body level with ∼100 μm resolution. Moreover, our microscopic implementation of RS-PAT is capable of imaging mammalian cells with a sub-diffraction lateral resolution of ∼140 nm and axial resolution of ∼400 nm, which are respectively ∼2-fold and ∼75-fold finer than those of our conventional photoacoustic microscopy. Overall, RS-PAT is a new and promising imaging technology for studying biological processes at different length scales.

Authors
Yao, J; Kaberniuk, AA; Li, L; Shcherbakova, DM; Zhang, R; Wang, L; Li, G; Verkhusha, VV; Wanga, LV
MLA Citation
Yao, J, Kaberniuk, AA, Li, L, Shcherbakova, DM, Zhang, R, Wang, L, Li, G, Verkhusha, VV, and Wanga, LV. "Reversibly switchable photoacoustic tomography using a genetically encoded near-infrared phytochrome." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9708
Publish Date
2016
DOI
10.1117/12.2229156

Nanoparticles for photoacoustic imaging of vasculature

© Springer International Publishing Switzerland 2017. Photoacoustic imaging (PAI) is a multi-scale, multi-contrast biomedical imaging modality that can provide anatomical, functional, metabolic, and molecular information about tissue. PAI offers up to submicron resolution and several centimeters penetration depth, employing various endogenous or exogenous contrasts. In particular, because nanoparticles strongly absorb near infrared light, they enable high-contrast PAI with improved detection sensitivity at depths. In this chapter, we review the use of nanoparticles to enhance the performance of PAI in a wide range of biomedical applications, in particular in imaging vasculature. By using engineered nanoparticles with different structures and functions, PAI can target specific molecules in disease associated endothelial cells. By manipulating nanoparticles with light or ultrasound, PAI can also guide therapy. Overall, nanoparticle-enhanced PAI shows promising potential for high-sensitivity, deep-tissue imaging, especially for vasculature imaging.

Authors
Zhou, M; Li, L; Yao, J; Bouchard, RR; Wang, LV; Li, C
MLA Citation
Zhou, M, Li, L, Yao, J, Bouchard, RR, Wang, LV, and Li, C. "Nanoparticles for photoacoustic imaging of vasculature." Design and Applications of Nanoparticles in Biomedical Imaging. January 1, 2016. 337-356.
Source
scopus
Publish Date
2016
Start Page
337
End Page
356
DOI
10.1007/978-3-319-42169-8_16

Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe.

Photoacoustic tomography (PAT) of genetically encoded probes allows for imaging of targeted biological processes deep in tissues with high spatial resolution; however, high background signals from blood can limit the achievable detection sensitivity. Here we describe a reversibly switchable nonfluorescent bacterial phytochrome for use in multiscale photoacoustic imaging, BphP1, with the most red-shifted absorption among genetically encoded probes. BphP1 binds a heme-derived biliverdin chromophore and is reversibly photoconvertible between red and near-infrared light-absorption states. We combined single-wavelength PAT with efficient BphP1 photoswitching, which enabled differential imaging with substantially decreased background signals, enhanced detection sensitivity, increased penetration depth and improved spatial resolution. We monitored tumor growth and metastasis with ∼ 100-μm resolution at depths approaching 10 mm using photoacoustic computed tomography, and we imaged individual cancer cells with a suboptical-diffraction resolution of ∼ 140 nm using photoacoustic microscopy. This technology is promising for biomedical studies at several scales.

Authors
Yao, J; Kaberniuk, AA; Li, L; Shcherbakova, DM; Zhang, R; Wang, L; Li, G; Verkhusha, VV; Wang, LV
MLA Citation
Yao, J, Kaberniuk, AA, Li, L, Shcherbakova, DM, Zhang, R, Wang, L, Li, G, Verkhusha, VV, and Wang, LV. "Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe." Nature methods 13.1 (January 2016): 67-73.
Website
http://hdl.handle.net/10161/12772
PMID
26550774
Source
epmc
Published In
Nature Methods
Volume
13
Issue
1
Publish Date
2016
Start Page
67
End Page
73
DOI
10.1038/nmeth.3656

High-speed label-free functional photoacoustic microscopy of mouse brain in action.

We present fast functional photoacoustic microscopy (PAM) for three-dimensional high-resolution, high-speed imaging of the mouse brain, complementary to other imaging modalities. We implemented a single-wavelength pulse-width-based method with a one-dimensional imaging rate of 100 kHz to image blood oxygenation with capillary-level resolution. We applied PAM to image the vascular morphology, blood oxygenation, blood flow and oxygen metabolism in both resting and stimulated states in the mouse brain.

Authors
Yao, J; Wang, L; Yang, J-M; Maslov, KI; Wong, TTW; Li, L; Huang, C-H; Zou, J; Wang, LV
MLA Citation
Yao, J, Wang, L, Yang, J-M, Maslov, KI, Wong, TTW, Li, L, Huang, C-H, Zou, J, and Wang, LV. "High-speed label-free functional photoacoustic microscopy of mouse brain in action." Nature methods 12.5 (May 2015): 407-410.
Website
http://hdl.handle.net/10161/12773
PMID
25822799
Source
epmc
Published In
Nature Methods
Volume
12
Issue
5
Publish Date
2015
Start Page
407
End Page
410
DOI
10.1038/nmeth.3336

Photoacoustic microscopy: superdepth, superresolution, and superb contrast.

Since its invention in the 17th century, optical microscopy has revolutionized biomedical studies by scrutinizing the biological realm on cellular levels, taking advantage of its excellent light-focusing capability. However, most biological tissues scatter light highly. As light travels in tissue, cumulative scattering events cause the photons to lose their original propagation direction and, thus, their ability to be focused, which has largely limited the penetration depth of optical microscopy. Conventional planar optical microscopy can provide penetration of only ~100 ?m before photons begin to be scattered. The penetration of modern optical microcopy, such as confocal microscopy and multiphoton microscopy, is still limited to approximately the optical diffusion limit (~1 mm in the skin as approximated by one optical transport mean free path), where scattered photons retain a strong memory of the original propagation direction. So far, it still remains a challenge for pure optical methods to achieve high-resolution in vivo imaging beyond the diffusion limit (i.e., superdepth imaging).

Authors
Yao, J; Song, L; Wang, LV
MLA Citation
Yao, J, Song, L, and Wang, LV. "Photoacoustic microscopy: superdepth, superresolution, and superb contrast." IEEE pulse 6.3 (May 2015): 34-37.
PMID
25974913
Source
epmc
Published In
IEEE Pulse
Volume
6
Issue
3
Publish Date
2015
Start Page
34
End Page
37
DOI
10.1109/mpul.2015.2409100

Fast functional photoacoustic microscopy of mouse brain

© OSA 2015. We have developed fast functional photoacoustic microscopy (ffPAM). which can be utilized for three-dimensional morphological, functional, flow dynamic and metabolic mouse brain imaging through an intact skull with endogenous contrast only.

Authors
Yao, J; Yang, JM; Waiig, L; Zou, J; Waug, LY
MLA Citation
Yao, J, Yang, JM, Waiig, L, Zou, J, and Waug, LY. "Fast functional photoacoustic microscopy of mouse brain." January 1, 2015.
Source
scopus
Published In
Optics and the Brain, BRAIN 2015
Publish Date
2015

Photoacoustic imaging of single circulating melanoma cells in vivo

© 2015 SPIE. Melanoma, one of the most common types of skin cancer, has a high mortality rate, mainly due to a high propensity for tumor metastasis. The presence of circulating tumor cells (CTCs) is a potential predictor for metastasis. Label-free imaging of single circulating melanoma cells in vivo provides rich information on tumor progress. Here we present photoacoustic microscopy of single melanoma cells in living animals. We used a fast-scanning optical-resolution photoacoustic microscope to image the microvasculature in mouse ears. The imaging system has sub-cellular spatial resolution and works in reflection mode. A fast-scanning mirror allows the system to acquire fast volumetric images over a large field of view. A 500-kHz pulsed laser was used to image blood and CTCs. Single circulating melanoma cells were imaged in both capillaries and trunk vessels in living animals. These high-resolution images may be used in early detection of CTCs with potentially high sensitivity. In addition, this technique enables in vivo study of tumor cell extravasation from a primary tumor, which addresses an urgent pre-clinical need.

Authors
Wang, L; Yao, J; Zhang, R; Xu, S; Li, G; Zou, J; Wang, LV
MLA Citation
Wang, L, Yao, J, Zhang, R, Xu, S, Li, G, Zou, J, and Wang, LV. "Photoacoustic imaging of single circulating melanoma cells in vivo." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9323
Publish Date
2015
DOI
10.1117/12.2076987

Photo-imprint super-resolution photoacoustic microscopy

© 2015 SPIE. Combining the absorption-based photoacoustic effect and intensity-dependent photobleaching effect, we demonstrate a simple method for super-resolution photoacoustic imaging of both fluorescent and non-fluorescent samples. Our method is based on a double-excitation process, where the first excitation pulse partially and inhomogeneously bleaches the molecules in the diffraction-limited excitation volume, thus biasing the signal contributions from a second excitation pulse striking the same region. By scanning the excitation beam, we performed three-dimensional sub-diffraction imaging of varied fluorescent and non-fluorescent species. A lateral resolution of 80 nm and an axial resolution of 370 nm have been demonstrated. This technique has the potential to enable label-free super-resolution imaging, and can be transferred to other optical imaging modalities or combined with other super-resolution methods.

Authors
Yao, J; Wang, L; Li, C; Zhang, C; Wang, LV
MLA Citation
Yao, J, Wang, L, Li, C, Zhang, C, and Wang, LV. "Photo-imprint super-resolution photoacoustic microscopy." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9323
Publish Date
2015
DOI
10.1117/12.2077350

Label-free optical-resolution photoacoustic endomicroscopy in vivo

© 2015 SPIE. Intravital microscopy techniques have become increasingly important in biomedical research because they can provide unique microscopic views of various biological or disease developmental processes in situ. Here we present an optical-resolution photoacoustic endomicroscopy (OR-PAEM) system that visualizes internal organs with a much finer resolution than conventional acoustic-resolution photoacoustic endoscopy systems. By combining gradient index (GRIN) lens-based optical focusing and ultrasonic ring transducer-based acoustic focusing, we achieved a transverse resolution as fine as ∼10 μm at an optical working distance of 6.5 mm. The OR-PAEM system's high-resolution intravital imaging capability is demonstrated through animal experiments.

Authors
Yang, JM; Li, C; Chen, R; Rao, B; Yao, J; Yeh, CH; Danielli, A; Maslov, K; Zhou, Q; Shung, KK; Wang, LV
MLA Citation
Yang, JM, Li, C, Chen, R, Rao, B, Yao, J, Yeh, CH, Danielli, A, Maslov, K, Zhou, Q, Shung, KK, and Wang, LV. "Label-free optical-resolution photoacoustic endomicroscopy in vivo." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9323
Publish Date
2015
DOI
10.1117/12.2080224

Three-dimensional photoacoustic and ultrasonic endoscopic imaging of two rabbit esophagi

© 2015 SPIE. The addition of photoacoustic endoscopy to conventional endoscopic ultrasound offers imaging capabilities that may improve diagnosis and clinical care of gastrointestinal tract diseases. In this study, using a 3.8-mm diameter dual-mode photoacoustic and ultrasonic endoscopic probe, we investigated photoacoustic and ultrasonic image features of rabbit esophagi. Specifically, we performed ex vivo imaging of intact rabbit esophagi and correlated the acquired images with histology. Without motion artifact-based limitations, we were able to utilize the full resolving power of the endoscopic device and acquire the first three-dimensional vasculature map of the esophagus and mediastinum, along with coregistered tissue density information. Here, we present the experimental results and discuss potential clinical applications of the technique.

Authors
Yang, JM; Favazza, C; Yao, J; Chen, R; Zhou, Q; Shung, KK; Wang, LV
MLA Citation
Yang, JM, Favazza, C, Yao, J, Chen, R, Zhou, Q, Shung, KK, and Wang, LV. "Three-dimensional photoacoustic and ultrasonic endoscopic imaging of two rabbit esophagi." January 1, 2015.
Source
scopus
Published In
Proceedings of SPIE
Volume
9323
Publish Date
2015
DOI
10.1117/12.2080294

Photoacoustic correlation spectroscopy for calibration-free absolute quantification of particle concentration

Currently, laser fluence calibration is typically required for quantitative measurement of particle concentration in photoacoustic microscopy. In this paper, we present another quantitative approach to measure absolute absorber concentrations by photoacoustic correlation spectroscopy. The proposed method is based on the fact that the Brownian motion induces particle count fluctuation in the detection volume. We first derived a theoretical model for photoacoustic signals and then applied our method to quantitative measurement of different concentrations of various particles. The experimental results agreed well with the predictions from the theoretical model, suggesting that our method can be used for absolute particle concentrations measurement. © 2014 SPIE.

Authors
Zhou, Y; Yao, J; Maslov, KI; Wang, LV
MLA Citation
Zhou, Y, Yao, J, Maslov, KI, and Wang, LV. "Photoacoustic correlation spectroscopy for calibration-free absolute quantification of particle concentration." January 1, 2014.
Source
scopus
Published In
Proceedings of SPIE
Volume
8943
Publish Date
2014
DOI
10.1117/12.2036635

Photoacoustic Doppler axial flow measurement of homogenous media using structured illumination

We propose time and frequency domain methods for homogenous flow measurement based on the photoacoustic Doppler effect. Excited by spatially modulated laser pulses, the flowing medium induces a Doppler frequency shift in the received photoacoustic signals. The frequency shift is proportional to the component of the flow speed projected onto the acoustic beam axis. These methods do not rely on particle heterogeneity in the medium. A red-ink phantom flowing in a tube immersed in water was used to validate the methods in both frequency and time domains. © 2014 SPIE.

Authors
Zhang, R; Yao, J; Maslov, KI; Wang, LV
MLA Citation
Zhang, R, Yao, J, Maslov, KI, and Wang, LV. "Photoacoustic Doppler axial flow measurement of homogenous media using structured illumination." January 1, 2014.
Source
scopus
Published In
Proceedings of SPIE
Volume
8943
Publish Date
2014
DOI
10.1117/12.2038356

Photoacoustic microscopy with enhanced resolution and imaging depth aided by optical clearing

Both the spatial resolution and maximum penetration depth of optical-resolution photoacoustic microscopy (ORPAM) deteriorate sharply with depth due to strong light scattering in tissue. To reduce tissue scattering, we propose to use glycerol as an optical clearing agent in OR-PAM. Our results show that the imaging performance of OR-PAM can be greatly enhanced by optical clearing both in vitro and in vivo. © 2014 SPIE.

Authors
Zhou, Y; Yao, J; Wang, LV
MLA Citation
Zhou, Y, Yao, J, and Wang, LV. "Photoacoustic microscopy with enhanced resolution and imaging depth aided by optical clearing." January 1, 2014.
Source
scopus
Published In
Proceedings of SPIE
Volume
8943
Publish Date
2014
DOI
10.1117/12.2036636

Photoacoustic tomography: principles and advances.

Photoacoustic tomography (PAT) is an emerging imaging modality that shows great potential for preclinical research and clinical practice. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous chromophores, such as oxy-hemoglobin and deoxy-hemoglobin, or exogenous contrast agents, such as organic dyes and nanoparticles. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Over the past decade, the photoacoustic technique has been evolving rapidly, leading to a variety of exciting discoveries and applications. This review covers the basic principles of PAT and its different implementations. Strengths of PAT are highlighted, along with the most recent imaging results.

Authors
Xia, J; Yao, J; Wang, LV
MLA Citation
Xia, J, Yao, J, and Wang, LV. "Photoacoustic tomography: principles and advances." Electromagnetic waves (Cambridge, Mass.) 147 (January 2014): 1-22.
Website
http://hdl.handle.net/10161/12771
PMID
25642127
Source
epmc
Published In
Progress in Electromagnetics Research
Volume
147
Publish Date
2014
Start Page
1
End Page
22

Multi-parametric quantitative microvascular imaging with optical-resolution photoacoustic microscopy in vivo.

Many diseases involve either the formation of new blood vessels (e.g., tumor angiogenesis) or the damage of existing ones (e.g., diabetic retinopathy) at the microcirculation level. Optical-resolution photoacoustic microscopy (OR-PAM), capable of imaging microvessels in 3D in vivo down to individual capillaries using endogenous contrast, has the potential to reveal microvascular information critical to the diagnosis and staging of microcirculation-related diseases. In this study, we have developed a dedicated microvascular quantification (MQ) algorithm for OR-PAM to automatically quantify multiple microvascular morphological parameters in parallel, including the vessel diameter distribution, the microvessel density, the vascular tortuosity, and the fractal dimension. The algorithm has been tested on in vivo OR-PAM images of a healthy mouse, demonstrating high accuracy for microvascular segmentation and quantification. The developed MQ algorithm for OR-PAM may greatly facilitate quantitative imaging of tumor angiogenesis and many other microcirculation related diseases in vivo.

Authors
Yang, Z; Chen, J; Yao, J; Lin, R; Meng, J; Liu, C; Yang, J; Li, X; Wang, L; Song, L
MLA Citation
Yang, Z, Chen, J, Yao, J, Lin, R, Meng, J, Liu, C, Yang, J, Li, X, Wang, L, and Song, L. "Multi-parametric quantitative microvascular imaging with optical-resolution photoacoustic microscopy in vivo." January 2014.
PMID
24515157
Source
epmc
Published In
Optics express
Volume
22
Issue
2
Publish Date
2014
Start Page
1500
End Page
1511
DOI
10.1364/oe.22.001500

Ultrasound-heated photoacoustic flowmetry.

We report the development of photoacoustic flowmetry assisted by high-intensity focused ultrasound (HIFU). This novel method employs HIFU to generate a heating impulse in the flow medium, followed by photoacoustic monitoring of the thermal decay process. Photoacoustic flowmetry in a continuous medium remains a challenge in the optical diffusive regime. Here, both the HIFU heating and photoacoustic detection can focus at depths beyond the optical diffusion limit (~1 mm in soft tissue). This method can be applied to a continuous medium, i.e., a medium without discrete scatterers or absorbers resolvable by photoacoustic imaging. Flow speeds up to 41 mm·s-1 have been experimentally measured in a blood phantom covered by 1.5-mm-thick tissue.

Authors
Wang, L; Yao, J; Maslov, KI; Xing, W; Wang, LV
MLA Citation
Wang, L, Yao, J, Maslov, KI, Xing, W, and Wang, LV. "Ultrasound-heated photoacoustic flowmetry." Journal of Biomedical Optics 18.11 (November 2013): 117003-.
PMID
24194064
Source
epmc
Published In
Journal of Biomedical Optics
Volume
18
Issue
11
Publish Date
2013
Start Page
117003
DOI
10.1117/1.jbo.18.11.117003

Photoacoustic Microscopy.

Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (~1 mm in soft tissue). With its excellent scalability, PAM can provide high-resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering-based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence-based methods, such as wide-field, confocal, and multi-photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state-of-the-art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.

Authors
Yao, J; Wang, LV
MLA Citation
Yao, J, and Wang, LV. "Photoacoustic Microscopy." Laser & photonics reviews 7.5 (September 2013).
PMID
24416085
Source
epmc
Published In
Laser & Photonics Reviews
Volume
7
Issue
5
Publish Date
2013
DOI
10.1002/lpor.201200060

Structured-illumination photoacoustic Doppler flowmetry of axial flow in homogeneous scattering media.

We propose a method for photoacoustic flow measurement based on the Doppler effect from a flowing homogeneous medium. Excited by spatially modulated laser pulses, the flowing medium induces a Doppler frequency shift in the received photoacoustic signals. The frequency shift is proportional to the component of the flow speed projected onto the acoustic beam axis, and the sign of the shift reflects the flow direction. Unlike conventional flowmetry, this method does not rely on particle heterogeneity in the medium; thus, it can tolerate extremely high particle density. A red-ink phantom flowing in a tube immersed in water was used to validate the method in both the frequency and time domains. The phantom flow immersed in an intralipid solution was also measured.

Authors
Zhang, R; Yao, J; Maslov, KI; Wang, LV
MLA Citation
Zhang, R, Yao, J, Maslov, KI, and Wang, LV. "Structured-illumination photoacoustic Doppler flowmetry of axial flow in homogeneous scattering media." Applied physics letters 103.9 (August 28, 2013): 94101-.
PMID
24065864
Source
epmc
Published In
Applied Physics Letters
Volume
103
Issue
9
Publish Date
2013
Start Page
94101
DOI
10.1063/1.4819735

Optical clearing-aided photoacoustic microscopy with enhanced resolution and imaging depth.

Due to strong light scattering in tissue, both the spatial resolution and maximum penetration depth of optical-resolution photoacoustic microscopy (OR-PAM) deteriorate sharply with depth. To reduce tissue scattering, we propose to use glycerol as an optical clearing agent in OR-PAM. Our results show that the imaging performance of OR-PAM can be greatly enhanced by optical clearing both in vitro and in vivo.

Authors
Zhou, Y; Yao, J; Wang, LV
MLA Citation
Zhou, Y, Yao, J, and Wang, LV. "Optical clearing-aided photoacoustic microscopy with enhanced resolution and imaging depth." Optics letters 38.14 (July 2013): 2592-2595.
PMID
23939121
Source
epmc
Published In
Optics Letters
Volume
38
Issue
14
Publish Date
2013
Start Page
2592
End Page
2595
DOI
10.1364/ol.38.002592

A water-immersible 2-Axis scanning mirror microsystem for ultrasound and photoacoustic microscopic imaging applications

For both ultrasound and photoacoustic microscopic imaging, a fast scanning ability is required, whereas the liquid environment for acoustic propagation limits the usage of traditional MEMS scanning mirrors. In this paper, a new waterimmersible scanning mirror microsystem has been designed, fabricated and tested. To achieve reliable underwater scanning, flexible polymer torsion hinges fabricated by laser micromachining were used to support the reflective silicon mirror plate. Two efficient electromagnetic microactuators consisting of compact RF choke inductors and high-strength neodymium magnet disc were constructed to drive the silicon mirror plate around a fast axis and a slow axis, respectively. The performance of the water-immersible scanning mirror microsystem in both air and water were tested using the laser tracing method. For the fast axis, the resonance frequency reached 224 Hz in air and 164 Hz in water, respectively. The scanning angles in air and water under ±10 V AC driving (at the resonance frequencies) were ±13.6° and ±10°. The scanning angles in both air and water under ±16 V DC driving were ±12°. For the slow axis, the resonance frequency reached 55 Hz in air and 38 Hz in water, respectively. The scanning angles in air and water under ±10 V AC driving (at the resonance frequencies) were ±8.5° and ±6°. The scanning angles in both air and water under ±10 V DC driving were ± 6.5°. The feasibility of using such a water-immersible scanning mirror microsystem for scanning ultrasound microscopic (SAM) imaging has been demonstrated with a 25-MHz ultrasound pulse/echo system and a target consisting of three optical fibers. © 2013 SPIE.

Authors
Huang, CH; Yao, J; Wang, LV; Zou, J
MLA Citation
Huang, CH, Yao, J, Wang, LV, and Zou, J. "A water-immersible 2-Axis scanning mirror microsystem for ultrasound and photoacoustic microscopic imaging applications." June 12, 2013.
Source
scopus
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
8616
Publish Date
2013
DOI
10.1117/12.2003087

Up-regulation of hypoxia-inducible factor 1 alpha and hemodynamic responses following massive small bowel resection.

Massive small bowel resection (SBR) results in an adaptive response within the remnant bowel. We have previously shown an immediate reduction in intestinal blood flow and oxygen saturation (sO2) after SBR. We therefore sought to determine the duration of resection-induced intestinal hypoxia and expression of hypoxia-inducible factors (HIFs) following SBR.C57B6 mice were subjected to 50% proximal SBR or a sham procedure. Photoacoustic microscopy (PAM) was used to measure blood flow and sO2 on postoperative days (PODs) 1, 3, and 7. Ileal tissue was harvested 6h postoperatively and on PODs 1 and 2, and HIF1α, HIF2α, and VEGF mRNA expression were assessed via RT-PCR. A p value of less than 0.05 was considered significant.Following SBR, reduction in intestinal blood flow persists for 24h and is followed with hyperemia by POD 3. The immediate reduction in venous sO2 and increased tissue oxygen utilization continued through POD 7. Enhanced expression of HIF1α was demonstrated 6h following SBR.Massive SBR results in an immediate relative hypoxic state within the remnant bowel with early enhanced expression of HIF1α. On POD 7, increased tissue oxygen extraction and elevated blood flow persist in the adapting intestine.

Authors
Rowland, KJ; Yao, J; Wang, L; Erwin, CR; Maslov, KI; Wang, LV; Warner, BW
MLA Citation
Rowland, KJ, Yao, J, Wang, L, Erwin, CR, Maslov, KI, Wang, LV, and Warner, BW. "Up-regulation of hypoxia-inducible factor 1 alpha and hemodynamic responses following massive small bowel resection." Journal of pediatric surgery 48.6 (June 2013): 1330-1339.
PMID
23845627
Source
epmc
Published In
Journal of Pediatric Surgery
Volume
48
Issue
6
Publish Date
2013
Start Page
1330
End Page
1339
DOI
10.1016/j.jpedsurg.2013.03.031

Photoacoustic microscopy with 7.6-μm axial resolution

The axial resolution of photoacoustic microscopy (PAM) is much lower than its lateral resolution, which resolves down to the submicron level. Here we achieved so far the highest axial resolution of 7.6 μm by using a commercial 125 MHz ultrasonic transducer for signal detection, followed by the Wiener deconvolution for signal processing. The axial resolution was validated by imaging two layers of red ink in a wedge shape. Melanoma cells were imaged ex vivo with high axial resolution. Compared with a PAM system with a 50 MHz ultrasonic transducer, our high-axial-resolution PAM system resolved the blood vessels in mouse ears in vivo much more clearly in the depth direction. © 2013 Copyright SPIE.

Authors
Zhang, C; Maslov, K; Yao, J; Wang, LV
MLA Citation
Zhang, C, Maslov, K, Yao, J, and Wang, LV. "Photoacoustic microscopy with 7.6-μm axial resolution." May 28, 2013.
Source
scopus
Published In
Proceedings of SPIE
Volume
8581
Publish Date
2013
DOI
10.1117/12.2003248

Photoacoustic endoscopic imaging of the rabbit mediastinum

Like ultrasound endoscopy, photoacoustic endoscopy (PAE) could become a valuable addition to clinical practice due to its deep imaging capability. Results from our recent in vivo transesophageal endoscopic imaging study on rabbits demonstrate the technique's capability to image major organs in the mediastinal region, such as the lung, trachea, and cardiovascular systems. Here, we present various features from photoacoustic images from the mediastinal region of several rabbits and discuss possible clinical contributions of this technique and directions of future technology development. © 2013 Copyright SPIE.

Authors
Yang, JM; Favazza, C; Chen, R; Yao, J; Cai, X; Li, C; Maslov, K; Zhou, Q; Shung, KK; Wang, LV
MLA Citation
Yang, JM, Favazza, C, Chen, R, Yao, J, Cai, X, Li, C, Maslov, K, Zhou, Q, Shung, KK, and Wang, LV. "Photoacoustic endoscopic imaging of the rabbit mediastinum." May 28, 2013.
Source
scopus
Published In
Proceedings of SPIE
Volume
8581
Publish Date
2013
DOI
10.1117/12.2004980

Photoacoustic microscopy of neovascularization in three-dimensional porous scaffolds

It is a challenge to non-invasively visualize in vivo the neovascularization in a three-dimensional (3D) scaffold with high spatial resolution and deep penetration depth. Here we used photoacoustic microscopy (PAM) to chronically monitor neovascularization in an inverse opal scaffold implanted in a mouse model for up to six weeks. The neovasculature was observed to develop gradually in the same mouse. These blood vessels not only grew on top of the implanted scaffold but also penetrated into the scaffold. The PAM system offered a lateral resolution of ∼45 μm and a penetration depth of ∼3 mm into the scaffold/tissue construct. By using the 3D PAM data, we further quantified the vessel area as a function of time. © 2013 Copyright SPIE.

Authors
Cai, X; Zhang, Y; Li, L; Choi, SW; MacEwan, MR; Yao, J; Kim, C; Xia, Y; Wang, LV
MLA Citation
Cai, X, Zhang, Y, Li, L, Choi, SW, MacEwan, MR, Yao, J, Kim, C, Xia, Y, and Wang, LV. "Photoacoustic microscopy of neovascularization in three-dimensional porous scaffolds." May 28, 2013.
Source
scopus
Published In
Proceedings of SPIE
Volume
8581
Publish Date
2013
DOI
10.1117/12.2005236

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism. © 2013 Copyright SPIE.

Authors
Yao, J; Xia, J; Maslov, K; Avanaki, MRN; Tsytsarev, V; Demchenko, AV; Wang, LV
MLA Citation
Yao, J, Xia, J, Maslov, K, Avanaki, MRN, Tsytsarev, V, Demchenko, AV, and Wang, LV. "Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo." May 28, 2013.
Source
scopus
Published In
Proceedings of SPIE
Volume
8581
Publish Date
2013
DOI
10.1117/12.2005645

Water-Immersible MEMS scanning mirror designed for wide-field fast-scanning photoacoustic microscopy

By offering images with high spatial resolution and unique optical absorption contrast, optical-resolution photoacoustic microscopy (OR-PAM) has gained increasing attention in biomedical research. Recent developments in OR-PAM have improved its imaging speed, but have sacrificed either the detection sensitivity or field of view or both. We have developed a wide-field fast-scanning OR-PAM by using a water-immersible MEMS scanning mirror (MEMS-ORPAM). Made of silicon with a gold coating, the MEMS mirror plate can reflect both optical and acoustic beams. Because it uses an electromagnetic driving force, the whole MEMS scanning system can be submerged in water. In MEMS-ORPAM, the optical and acoustic beams are confocally configured and simultaneously steered, which ensures uniform detection sensitivity. A B-scan imaging speed as high as 400 Hz can be achieved over a 3 mm scanning range. A diffraction-limited lateral resolution of 2.4 μm in water and a maximum imaging depth of 1.1 mm in soft tissue have been experimentally determined. Using the system, we imaged the flow dynamics of both red blood cells and carbon particles in a mouse ear in vivo. By using Evans blue dye as the contrast agent, we also imaged the flow dynamics of lymphatic vessels in a mouse tail in vivo. The results show that MEMS-OR-PAM could be a powerful tool for studying highly dynamic and time-sensitive biological phenomena. © 2013 Copyright SPIE.

Authors
Yao, J; Huang, CH; Martel, C; Maslov, KI; Wang, L; Yang, JM; Gao, L; Randolph, G; Zou, J; Wang, LV
MLA Citation
Yao, J, Huang, CH, Martel, C, Maslov, KI, Wang, L, Yang, JM, Gao, L, Randolph, G, Zou, J, and Wang, LV. "Water-Immersible MEMS scanning mirror designed for wide-field fast-scanning photoacoustic microscopy." May 28, 2013.
Source
scopus
Published In
Proceedings of SPIE
Volume
8581
Publish Date
2013
DOI
10.1117/12.2005669

A water-immersible 2-axis scanning mirror microsystem for ultrasound andha photoacoustic microscopic imaging applications

Authors
Huang, C-H; Yao, J; Wang, LV; Zou, J
MLA Citation
Huang, C-H, Yao, J, Wang, LV, and Zou, J. "A water-immersible 2-axis scanning mirror microsystem for ultrasound andha photoacoustic microscopic imaging applications." Microsystem Technologies 19.4 (April 2013): 577-582.
Source
crossref
Published In
Microsystem Technologies
Volume
19
Issue
4
Publish Date
2013
Start Page
577
End Page
582
DOI
10.1007/s00542-012-1660-4

Investigation of neovascularization in three-dimensional porous scaffolds in vivo by a combination of multiscale photoacoustic microscopy and optical coherence tomography.

It is a grand challenge to visualize and assess in vivo neovascularization in a three-dimensional (3D) scaffold noninvasively, together with high spatial resolution and deep penetration depth. Here we used multiscale photoacoustic microscopy (PAM), including acoustic-resolution PAM (AR-PAM) and optical-resolution PAM (OR-PAM), to chronically monitor neovascularization in an inverse opal scaffold implanted in a mouse model up to 6 weeks by taking advantage of the optical absorption contrast intrinsic to hemoglobin molecules in red blood cells. By combining with optical coherence tomography (OCT) based on optical scattering contrast, we also demonstrated the capability to simultaneously image and analyze the vasculature and the scaffold in the same mouse. The hybrid system containing OR-PAM and OCT offered a fine lateral resolution of ∼5 μm and a penetration depth of ∼1 mm into the scaffold/tissue construct. AR-PAM further extended the penetration depth up to ∼3 mm at a lateral resolution of ∼45 μm. By quantifying the 3D PAM data, we further examined the effect of pore size (200 vs. 80 μm) of a scaffold on neovascularization. The data collected from PAM were consistent with those obtained from traditional invasive, labor-intensive histologic analyses.

Authors
Cai, X; Zhang, Y; Li, L; Choi, S-W; MacEwan, MR; Yao, J; Kim, C; Xia, Y; Wang, LV
MLA Citation
Cai, X, Zhang, Y, Li, L, Choi, S-W, MacEwan, MR, Yao, J, Kim, C, Xia, Y, and Wang, LV. "Investigation of neovascularization in three-dimensional porous scaffolds in vivo by a combination of multiscale photoacoustic microscopy and optical coherence tomography." Tissue engineering. Part C, Methods 19.3 (March 2013): 196-204.
PMID
22838500
Source
epmc
Published In
Tissue Engineering, Part C, Methods
Volume
19
Issue
3
Publish Date
2013
Start Page
196
End Page
204
DOI
10.1089/ten.tec.2012.0326

Multi-scale Multi-contrast Photoacoustic Microscopy

Photoacoustic microscopy (PAM) is a hybrid imaging technique that acoustically detects optical contrast via the photoacoustic effect. With its excellent scalability, PAM can simultaneously image anatomical, functional, molecular, flow dynamic, and metabolic contrasts in vivo. © OSA 2013.

Authors
Yao, J; Wang, LV
MLA Citation
Yao, J, and Wang, LV. "Multi-scale Multi-contrast Photoacoustic Microscopy." January 1, 2013.
Source
scopus
Published In
Optics InfoBase Conference Papers
Publish Date
2013

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo.

We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively decoupled by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area had a clear vascular pattern and spread wider than the somatosensory region. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

Authors
Yao, J; Xia, J; Maslov, KI; Nasiriavanaki, M; Tsytsarev, V; Demchenko, AV; Wang, LV
MLA Citation
Yao, J, Xia, J, Maslov, KI, Nasiriavanaki, M, Tsytsarev, V, Demchenko, AV, and Wang, LV. "Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo." NeuroImage 64 (January 2013): 257-266.
PMID
22940116
Source
epmc
Published In
NeuroImage
Volume
64
Publish Date
2013
Start Page
257
End Page
266
DOI
10.1016/j.neuroimage.2012.08.054

Water-Immersible MEMS scanning mirror enhanced optical-resolution photoacoustic microscopy

A fast scanning optical-resolution photoacoustic microscopy has been developed using a water-immersible MEMS mirror. A B-scan rate of 400 Hz over a 3 mm scanning range has been demonstrated in phantom studies. © OSA 2012.

Authors
Yao, J; Huang, CH; Maslov, KI; Wang, L; Gao, L; Zou, J; Wang, LV
MLA Citation
Yao, J, Huang, CH, Maslov, KI, Wang, L, Gao, L, Zou, J, and Wang, LV. "Water-Immersible MEMS scanning mirror enhanced optical-resolution photoacoustic microscopy." December 1, 2012.
Source
scopus
Published In
Biomedical Optics, BIOMED 2012
Publish Date
2012

Volumetric photoacoustic endoscopy

Photoacoustic endoscopy provides unique functional information through its broad spectroscopic imaging capability. The imaging results presented here suggest its potential for use as a comprehensive endoscopic tool in various medical applications. © 2012 Optical Society of America.

Authors
Yang, JM; Favazza, C; Chen, R; Yao, J; Cai, X; Maslov, K; Zhou, Q; Kirk Shung, K; Wang, LV
MLA Citation
Yang, JM, Favazza, C, Chen, R, Yao, J, Cai, X, Maslov, K, Zhou, Q, Kirk Shung, K, and Wang, LV. "Volumetric photoacoustic endoscopy." December 1, 2012.
Source
scopus
Published In
Biomedical Optics, BIOMED 2012
Publish Date
2012

In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer.

Photoacoustic microscopy has achieved submicron lateral resolution, but its axial resolution is much lower. Here an axial resolution of 7.6 μm, the highest axial resolution validated by experimental data, has been achieved by using a commercial 125 MHz ultrasonic transducer for signal detection followed by the Wiener deconvolution for signal processing. Limited by the working distance, the high-frequency ultrasonic transducer can penetrate 1.2 mm into biological tissue from the ultrasound detection side. At this depth, the signal-to-noise ratio decreases by 11 dB, and the axial resolution degrades by 36%. The new system was demonstrated in imaging melanoma cells ex vivo and mouse ears in vivo.

Authors
Zhang, C; Maslov, K; Yao, J; Wang, LV
MLA Citation
Zhang, C, Maslov, K, Yao, J, and Wang, LV. "In vivo photoacoustic microscopy with 7.6-µm axial resolution using a commercial 125-MHz ultrasonic transducer." Journal of biomedical optics 17.11 (November 2012): 116016-.
PMID
23123975
Source
epmc
Published In
Journal of Biomedical Optics
Volume
17
Issue
11
Publish Date
2012
Start Page
116016
DOI
10.1117/1.jbo.17.11.116016

A 2.5-mm diameter probe for photoacoustic and ultrasonic endoscopy.

We have created a 2.5-mm outer diameter integrated photo-acoustic and ultrasonic mini-probe which can be inserted into a standard video endoscope's instrument channel. A small-diameter focused ultrasonic transducer made of PMN-PT provides adequate signal sensitivity, and enables miniaturization of the probe. Additionally, this new endoscopic probe utilizes the same scanning mirror and micromotor-based built-in actuator described in our previous reports; however, the length of the rigid distal section of the new probe has been further reduced to ~35 mm. This paper describes the technical details of the mini-probe and presents experimental results that both quantify the imaging performance and demonstrate its in vivo imaging capability, which suggests that it could work as a mini-probe for certain clinical applications.

Authors
Yang, J-M; Chen, R; Favazza, C; Yao, J; Li, C; Hu, Z; Zhou, Q; Shung, KK; Wang, LV
MLA Citation
Yang, J-M, Chen, R, Favazza, C, Yao, J, Li, C, Hu, Z, Zhou, Q, Shung, KK, and Wang, LV. "A 2.5-mm diameter probe for photoacoustic and ultrasonic endoscopy." Optics express 20.21 (October 2012): 23944-23953.
PMID
23188360
Source
epmc
Published In
Optics express
Volume
20
Issue
21
Publish Date
2012
Start Page
23944
End Page
23953
DOI
10.1364/oe.20.023944

Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror.

By offering images with high spatial resolution and unique optical absorption contrast, optical-resolution photoacoustic microscopy (OR-PAM) has gained increasing attention in biomedical research. Recent developments in OR-PAM have improved its imaging speed, but have to sacrifice either the detection sensitivity or field of view or both. We have developed a wide-field fast-scanning OR-PAM by using a water-immersible microelectromechanical systems (MEMS) scanning mirror (MEMS-OR-PAM). In MEMS-OR-PAM, the optical and acoustic beams are confocally configured and simultaneously steered, which ensures the uniform detection sensitivity. A B-scan imaging speed as high as 400 Hz can be achieved over a 3 mm scanning range. Using the system, we imaged the flow dynamics of both red blood cells and carbon particles in a mouse ear in vivo. Presented results show that MEMS-OR-PAM could be a powerful tool for studying highly dynamic and time-sensitive biological phenomena.

Authors
Yao, J; Huang, C-H; Wang, L; Yang, J-M; Gao, L; Maslov, KI; Zou, J; Wang, LV
MLA Citation
Yao, J, Huang, C-H, Wang, L, Yang, J-M, Gao, L, Maslov, KI, Zou, J, and Wang, LV. "Wide-field fast-scanning photoacoustic microscopy based on a water-immersible MEMS scanning mirror." Journal of Biomedical Optics 17.8 (August 2012): 080505-080501.
PMID
23224156
Source
epmc
Published In
Journal of Biomedical Optics
Volume
17
Issue
8
Publish Date
2012
Start Page
080505
End Page
080501
DOI
10.1117/1.jbo.17.8.080505

Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo.

At present, clinicians routinely apply ultrasound endoscopy in a variety of interventional procedures that provide treatment solutions for diseased organs. Ultrasound endoscopy not only produces high-resolution images, but also is safe for clinical use and broadly applicable. However, for soft tissue imaging, its mechanical wave-based image contrast fundamentally limits its ability to provide physiologically specific functional information. By contrast, photoacoustic endoscopy possesses a unique combination of functional optical contrast and high spatial resolution at clinically relevant depths, ideal for imaging soft tissues. With these attributes, photoacoustic endoscopy can overcome the current limitations of ultrasound endoscopy. Moreover, the benefits of photoacoustic imaging do not come at the expense of existing ultrasound functions; photoacoustic endoscopy systems are inherently compatible with ultrasound imaging, thereby enabling multimodality imaging with complementary contrast. Here we present simultaneous photoacoustic and ultrasonic dual-mode endoscopy and show its ability to image internal organs in vivo, thus illustrating its potential clinical application.

Authors
Yang, J-M; Favazza, C; Chen, R; Yao, J; Cai, X; Maslov, K; Zhou, Q; Shung, KK; Wang, LV
MLA Citation
Yang, J-M, Favazza, C, Chen, R, Yao, J, Cai, X, Maslov, K, Zhou, Q, Shung, KK, and Wang, LV. "Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo." Nature medicine 18.8 (August 2012): 1297-1302.
PMID
22797808
Source
epmc
Published In
Nature Medicine
Volume
18
Issue
8
Publish Date
2012
Start Page
1297
End Page
1302
DOI
10.1038/nm.2823

In vivo photoacoustic tomography of total blood flow and potential imaging of cancer angiogenesis and hypermetabolism.

Blood flow is a key parameter in studying cancer angiogenesis and hypermetabolism. Current photoacoustic blood flow estimation methods focus on either the axial or transverse component of the flow vector. However, the Doppler angle (beam-to-flow angle) is needed to calculate the total flow speed, and it cannot always be estimated accurately in practice, especially when the system's axial and lateral resolutions are different. To overcome this problem, we propose a method to compute the total flow speed and Doppler angle by combining the axial and transverse flow measurements. The method has been verified by flowing bovine blood in a plastic tube at various speeds and Doppler angles. The error was experimentally determined to be less than 0.3 mm/s for total flow speed, and less than 158 for the Doppler angle. In addition, the method was tested in vivo on a mouse ear. We believe that the proposed method has the potential to be used for cancer angiogenesis and hypermetabolism imaging.

Authors
Yao, J; Maslov, KI; Wang, LV
MLA Citation
Yao, J, Maslov, KI, and Wang, LV. "In vivo photoacoustic tomography of total blood flow and potential imaging of cancer angiogenesis and hypermetabolism." Technology in cancer research & treatment 11.4 (August 2012): 301-307.
PMID
22417060
Source
epmc
Published In
Technology in cancer research & treatment
Volume
11
Issue
4
Publish Date
2012
Start Page
301
End Page
307
DOI
10.7785/tcrt.2012.500278

Immediate alterations in intestinal oxygen saturation and blood flow after massive small bowel resection as measured by photoacoustic microscopy.

Massive small bowel resection (SBR) results in villus angiogenesis and a critical adaptation response within the remnant bowel. Previous ex vivo studies of intestinal blood flow after SBR are conflicting. We sought to determine the effect of SBR on intestinal hemodynamics using photoacoustic microscopy, a noninvasive, label-free, high-resolution in vivo hybrid imaging modality.Photoacoustic microscopy was used to image the intestine microvascular system and measure blood flow and oxygen saturation (So(2)) of the terminal mesenteric arteriole and accompanying vein in C57BL6 mice (n = 7) before and immediately after a 50% proximal SBR. A P value of less than .05 was considered significant.Before SBR, arterial and venous So(2) were similar. Immediately after SBR, the venous So(2) decreased with an increase in the oxygen extraction fraction. In addition, the arterial and venous blood flow significantly decreased.Massive SBR results in an immediate reduction in intestinal blood flow and increase in tissue oxygen utilization. These physiologic changes are observed throughout the remnant small intestine. The contribution of these early hemodynamic alterations may contribute to the induction of villus angiogenesis and the pathogenesis of normal intestinal adaptation responses.

Authors
Rowland, KJ; Yao, J; Wang, L; Erwin, CR; Maslov, KI; Wang, LV; Warner, BW
MLA Citation
Rowland, KJ, Yao, J, Wang, L, Erwin, CR, Maslov, KI, Wang, LV, and Warner, BW. "Immediate alterations in intestinal oxygen saturation and blood flow after massive small bowel resection as measured by photoacoustic microscopy." Journal of pediatric surgery 47.6 (June 2012): 1143-1149.
PMID
22703784
Source
epmc
Published In
Journal of Pediatric Surgery
Volume
47
Issue
6
Publish Date
2012
Start Page
1143
End Page
1149
DOI
10.1016/j.jpedsurg.2012.03.020

Functional photoacoustic microscopy of diabetic vasculature.

We used functional photoacoustic microscopy to image diabetes-induced damage to the microvasculature. To produce an animal model for Type 1 diabetes, we used streptozotocin (STZ), which is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. A set number of ND4 Swiss Webster mice received intraperitoneal injections of STZ for five consecutive days at 50 mg/kg. Most mice developed a significant rise in blood glucose level (≈ 400 mg/dL) within three weeks of the first injection. Changes in vasculature and hemodynamics were monitored for six weeks. The mouse ear was imaged with an optical-resolution photoacoustic microscope at a main blood vessel branch from the root of the ear. There are noticeable and measurable changes associated with the disease, including decreased vessel diameter and possible occlusion due to vessel damage and polyurea. We also observed an increase in the blood flow speed in the vein and a decrease in the artery, which could be due to compensation for the dehydration and vessel diameter changes. Functional and metabolic parameters such as hemoglobin oxygen saturation, oxygen extraction fraction, and oxygen consumption rate were also measured, but showed no significant change.

Authors
Krumholz, A; Wang, L; Yao, J; Wang, LV
MLA Citation
Krumholz, A, Wang, L, Yao, J, and Wang, LV. "Functional photoacoustic microscopy of diabetic vasculature." Journal of biomedical optics 17.6 (June 2012): 060502-. (Letter)
PMID
22734725
Source
epmc
Published In
Journal of Biomedical Optics
Volume
17
Issue
6
Publish Date
2012
Start Page
060502
DOI
10.1117/1.jbo.17.6.060502

Double-illumination photoacoustic microscopy of intestinal hemodynamics following massive small bowel resection

Massive small bowel resection (SBR) results in villus angiogenesis and intestinal adaptation. The exact mechanism that causes intestinal villus angiogenesis remains unknown. We hypothesize that hemodynamic changes within the remnant bowel after SBR will trigger intestinal angiogenesis. To validate this, we used photoacoustic microscopy (PAM) to image the microvascular system of the intestine in C57B6 mice and to measure blood flow and oxygen saturation (sO 2 ) of a supplying artery and vein. Baseline measurements were made 6 cm proximal to the ileal-cecal junction (ICJ) prior to resection. A 50% proximal bowel resection was then performed, and measurements were again recorded at the same location immediately, 1, 3 and 7 days following resection. The results show that arterial and venous sO 2 were similar prior to SBR. Immediately following SBR, the arterial and venous sO 2 decreased by 14.3 ± 2.7% and 32.7 ± 6.6%, respectively, while the arterial and venous flow speed decreased by 62.9 ± 17.3% and 60.0 ± 20.1%, respectively. Such significant decreases in sO 2 and blood flow indicate a hypoxic state after SBR. Within one week after SBR, both sO 2 and blood flow speed had gradually recovered. By 7 days after SBR, arterial and venous sO 2 had increased to 101.0 ± 2.9% and 82.7 ± 7.3% of the baseline values, respectively, while arterial and venous flow speed had increased to 106.0 ± 21.4% and 150.0 ± 29.6% of the baseline values, respectively. Such increases in sO 2 and blood flow may result from angiogenesis following SBR. © 2012 SPIE.

Authors
Yao, J; Rowland, KJ; Wang, L; Maslov, KI; Warner, BW; Wang, LV
MLA Citation
Yao, J, Rowland, KJ, Wang, L, Maslov, KI, Warner, BW, and Wang, LV. "Double-illumination photoacoustic microscopy of intestinal hemodynamics following massive small bowel resection." April 9, 2012.
Source
scopus
Published In
Proceedings of SPIE
Volume
8223
Publish Date
2012
DOI
10.1117/12.909508

In vivo photoacoustic tomography of total blood flow and Doppler angle

As two hallmarks of cancer, angiogenesis and hypermetabolism are closely related to increased blood flow. Volumetric blood flow measurement is important to understanding the tumor microenvironment and developing new means to treat cancer. Current photoacoustic blood flow estimation methods focus on either the axial or transverse component of the flow vector. Here, we propose a method to compute the total flow speed and Doppler angle by combining the axial and transverse flow measurements. Both the components are measured in M-mode. Collating the A-lines side by side yields a 2D matrix. The columns are Hilbert transformed to compare the phases for the computation of the axial flow. The rows are Fourier transformed to quantify the bandwidth for the computation of the transverse flow. From the axial and transverse flow components, the total flow speed and Doppler angle can be derived. The method has been verified by flowing bovine blood in a plastic tube at various speeds from 0 to 7.5 mm/s and at Doppler angles from 30 to 330°. The measurement error for total flow speed was experimentally determined to be less than 0.3 mm/s; for the Doppler angle, it was less than 15°. In addition, the method was tested in vivo on a mouse ear. The advantage of this method is simplicity: No system modification or additional data acquisition is required to use our existing system. We believe that the proposed method has the potential to be used for cancer angiogenesis and hypermetabolism imaging. © 2012 SPIE.

Authors
Yao, J; Maslov, KI; Wang, LV
MLA Citation
Yao, J, Maslov, KI, and Wang, LV. "In vivo photoacoustic tomography of total blood flow and Doppler angle." April 9, 2012.
Source
scopus
Published In
Proceedings of SPIE
Volume
8223
Publish Date
2012
DOI
10.1117/12.909480

Functional photoacoustic microscopy of pH

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, imbalance of pH regulation may result from or result in serious illness. Even though the regulation system of pH is very robust, tissue pH can be altered in many diseases such as cancer, osteoporosis and diabetes mellitus. Traditional high-resolution optical imaging techniques, such as confocal microscopy, routinely image pH in cells and tissues using pH sensitive fluorescent dyes, which change their fluorescence properties with the surrounding pH. Since strong optical scattering in biological tissue blurs images at greater depths, high-resolution pH imaging is limited to penetration depths of 1mm. Here, we report photoacoustic microscopy (PAM) of commercially available pH-sensitive fluorescent dye in tissue phantoms. Using both opticalresolution photoacoustic microscopy (OR-PAM), and acoustic resolution photoacoustic microscopy (AR-PAM), we explored the possibility of recovering the pH values in tissue phantoms. In this paper, we demonstrate that PAM was capable of recovering pH values up to a depth of 2 mm, greater than possible with other forms of optical microscopy. © 2012 SPIE.

Authors
Chatni, MR; Yao, J; Danielli, A; Favazza, CP; Maslov, KI; Wang, LV
MLA Citation
Chatni, MR, Yao, J, Danielli, A, Favazza, CP, Maslov, KI, and Wang, LV. "Functional photoacoustic microscopy of pH." April 9, 2012.
Source
scopus
Published In
Proceedings of SPIE
Volume
8223
Publish Date
2012
DOI
10.1117/12.907685

Multi-contrast photoacoustic microscopy

We developed multi-contrast photoacoustic microscopy (PAM) for in vivo anatomical, functional, metabolic, and molecular imaging. This technical innovation enables comprehensive understanding of the tumor microenvironment. With multi-contrast PAM, we longitudinally determined tumor vascular anatomy, blood flow, oxygen saturation of hemoglobin, and oxygen extraction fraction. © 2012 SPIE.

Authors
Hu, S; Sohn, R; Lu, ZH; Soetikno, B; Zhong, Q; Yao, J; Maslov, K; Arbeit, JM; Wang, LV
MLA Citation
Hu, S, Sohn, R, Lu, ZH, Soetikno, B, Zhong, Q, Yao, J, Maslov, K, Arbeit, JM, and Wang, LV. "Multi-contrast photoacoustic microscopy." April 9, 2012.
Source
scopus
Published In
Proceedings of SPIE
Volume
8223
Publish Date
2012
DOI
10.1117/12.909754

Photoacoustic imaging of the near-infrared fluorescent protein iRFP in vivo

Genetically encoded probes powerfully and non-invasively target specific tissues, cells, and subcellular locations. iRFP, a novel near-infrared fluorescent protein with low quantum yield whose absorption and fluorescence maxima are located at wavelengths longer than the Q-band of hemoglobin absorption, is ideal for PAT. Here, we report on an in vitro comparison of iRFP with other far-red fluorescent proteins, and its use in imaging a mouse tumor xenograft model. In an in vivo experiment, we stably transfected iRFP into MTLn3 adenocarcinoma cells and injected them into the mammary fat pad of female SCID/NCr mice, then imaged the resulting tumors two and three weeks post injection. The contrast increase from the protein expression was high enough to clearly separate the tumor region from the rest of the animal. © 2012 SPIE.

Authors
Krumholz, A; Filonov, GS; Xia, J; Yao, J; Verkhusha, VV; Wang, LV
MLA Citation
Krumholz, A, Filonov, GS, Xia, J, Yao, J, Verkhusha, VV, and Wang, LV. "Photoacoustic imaging of the near-infrared fluorescent protein iRFP in vivo." April 9, 2012.
Source
scopus
Published In
Proceedings of SPIE
Volume
8223
Publish Date
2012
DOI
10.1117/12.908927

Toward dual-wavelength functional photoacoustic endoscopy: Laser and peripheral optical systems development

Photoacoustic endoscopy (PAE) provides unique functional information with high spatial resolution at super depths. The provision of functional information is predicated on its strong spectroscopic imaging ability, and its deep imaging capability is derived from its ultrasonic detection of diffused photon absorption. To accurately image functional physiological parameters, it is necessary to rapidly alternate laser pulses of sufficient energy and different wavelengths. In this study, we developed peripheral optical systems for PAE based on two identical pulsed-laser systems to achieve the fast laser wavelength switching that is essential for accurate functional imaging. Each laser system was comprised of a tunable dye laser pumped by a solid-state, diode-pumped Nd:YLF laser. Both systems deliver adequate energy at the scanning head of the endoscope for imaging biological tissue in the optically diffusive regime (∼0.3-0.6 mJ per pulse with a repetition rate of ∼1 kHz). In this paper, we introduce the employed laser systems and design of the light delivery optics, and present results from an ex vivo animal imaging experiment that validates the system's multi-wavelength functional imaging capability. © 2012 SPIE.

Authors
Yang, JM; Favazza, C; Chen, R; Yao, J; Cai, X; Maslov, K; Zhou, Q; Shung, KK; Wang, LV
MLA Citation
Yang, JM, Favazza, C, Chen, R, Yao, J, Cai, X, Maslov, K, Zhou, Q, Shung, KK, and Wang, LV. "Toward dual-wavelength functional photoacoustic endoscopy: Laser and peripheral optical systems development." April 9, 2012.
Source
scopus
Published In
Proceedings of SPIE
Volume
8223
Publish Date
2012
DOI
10.1117/12.909163

A 2.5-mm outer diameter photoacoustic endoscopic mini-probe based on a highly sensitive PMN-PT ultrasonic transducer

We have developed a 2.5-mm outer diameter photoacoustic endoscopic mini-probe to use in the instrument channel (typically 2.8 or 3.7 mm in diameter) of standard video endoscopes. To achieve adequate signal sensitivity, we fabricated a focused ultrasonic transducer using a highly-sensitive PMN-PT piezoelectric material. We quantified the PMN-PT transducer's operating parameters and validated the mini-probe's endoscopic imaging capability through an ex vivo imaging experiment on a rat colon. © 2012 SPIE.

Authors
Yang, JM; Chen, R; Favazza, C; Yao, J; Zhou, Q; Shung, KK; Wang, LV
MLA Citation
Yang, JM, Chen, R, Favazza, C, Yao, J, Zhou, Q, Shung, KK, and Wang, LV. "A 2.5-mm outer diameter photoacoustic endoscopic mini-probe based on a highly sensitive PMN-PT ultrasonic transducer." April 9, 2012.
Source
scopus
Published In
Proceedings of SPIE
Volume
8223
Publish Date
2012
DOI
10.1117/12.909207

Double-illumination photoacoustic microscopy.

Recent developments of optical-resolution photoacoustic microscopy (OR-PAM) have improved its spatial resolution and imaging speed. However, the penetration depth of OR-PAM is still limited to ~1 mm in tissue, owing to the strong tissue scattering. Here, we have developed double-illumination PAM (DI-PAM), which illuminates the sample from both top and bottom sides simultaneously. Through phantom and in vivo experiments, we have demonstrated for thin targets that DI-PAM has a penetration depth of ~2 mm in tissue at 532 nm and a focal zone of 260 μm, both significant improvements over traditional reflection or transmission-mode OR-PAM.

Authors
Yao, J; Maslov, KI; Puckett, ER; Rowland, KJ; Warner, BW; Wang, LV
MLA Citation
Yao, J, Maslov, KI, Puckett, ER, Rowland, KJ, Warner, BW, and Wang, LV. "Double-illumination photoacoustic microscopy." Optics letters 37.4 (February 2012): 659-661.
PMID
22344139
Source
epmc
Published In
Optics Letters
Volume
37
Issue
4
Publish Date
2012
Start Page
659
End Page
661
DOI
10.1364/ol.37.000659

Deep-tissue photoacoustic tomography of a genetically encoded near-infrared fluorescent probe.

Authors
Filonov, GS; Krumholz, A; Xia, J; Yao, J; Wang, LV; Verkhusha, VV
MLA Citation
Filonov, GS, Krumholz, A, Xia, J, Yao, J, Wang, LV, and Verkhusha, VV. "Deep-tissue photoacoustic tomography of a genetically encoded near-infrared fluorescent probe." Angewandte Chemie (International ed. in English) 51.6 (February 2012): 1448-1451.
PMID
22213541
Source
epmc
Published In
Angewandte Chemie International Edition
Volume
51
Issue
6
Publish Date
2012
Start Page
1448
End Page
1451
DOI
10.1002/anie.201107026

In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog.

Accurately locating epileptic foci has great importance in advancing the treatment of epilepsy. In this study, epileptic seizures were first induced by intracortical injection of 4-aminopyridine in rats. A fluorescent deoxyglucose substitute, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), was then continuously injected via the tail vein. Brain glucose metabolism was subsequently monitored by fluorescence imaging of 2-NBDG. The initial uptake rate of 2-NBDG at the injection site of 4-aminopyridine significantly exceeded that of the control injection site, which indicated local hypermetabolism induced by seizures. Our results show that 2-NBDG can be used for localizing epileptic foci.

Authors
Tsytsarev, V; Maslov, KI; Yao, J; Parameswar, AR; Demchenko, AV; Wang, LV
MLA Citation
Tsytsarev, V, Maslov, KI, Yao, J, Parameswar, AR, Demchenko, AV, and Wang, LV. "In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog." Journal of neuroscience methods 203.1 (January 2012): 136-140.
PMID
21939688
Source
epmc
Published In
Journal of Neuroscience Methods
Volume
203
Issue
1
Publish Date
2012
Start Page
136
End Page
140
DOI
10.1016/j.jneumeth.2011.09.005

Functional photoacoustic microscopy of pH.

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, an imbalance of pH regulation may result from or result in serious illness. In this paper, we report photoacoustic microscopy (PAM) of a commercially available pH-sensitive fluorescent dye (SNARF-5F carboxylic acid) in tissue phantoms. We demonstrated that PAM is capable of pH imaging in absolute values at tissue depths of up to 2.0 mm, greater than possible with other forms of optical microscopy.

Authors
Chatni, MR; Yao, J; Danielli, A; Favazza, CP; Maslov, KI; Wang, LV
MLA Citation
Chatni, MR, Yao, J, Danielli, A, Favazza, CP, Maslov, KI, and Wang, LV. "Functional photoacoustic microscopy of pH." Journal of Biomedical Optics 16.10 (October 2011): 100503-. (letter)
PMID
22029342
Source
epmc
Published In
Journal of Biomedical Optics
Volume
16
Issue
10
Publish Date
2011
Start Page
100503
DOI
10.1117/1.3644495

Photoacoustic tomography: fundamentals, advances and prospects.

Optical microscopy has been contributing to the development of life science for more than three centuries. However, due to strong optical scattering in tissue, its in vivo imaging ability has been restricted to studies at superficial depths. Advances in photoacoustic tomography (PAT) now allow multiscale imaging at depths from sub-millimeter to several centimeters, with spatial resolutions from sub-micrometer to sub-millimeter. Because of this high scalability and its unique optical absorption contrast, PAT is capable of performing anatomical, functional, molecular and fluid-dynamic imaging at various system levels, and is playing an increasingly important role in fundamental biological research and clinical practice. This review discusses recent technical progress in PAT and presents corresponding applications. It ends with a discussion of several prospects and their technical challenges.

Authors
Yao, J; Wang, LV
MLA Citation
Yao, J, and Wang, LV. "Photoacoustic tomography: fundamentals, advances and prospects." Contrast Media & Molecular Imaging 6.5 (September 2011): 332-345. (Review)
PMID
22025335
Source
epmc
Published In
Contrast Media & Molecular Imaging
Volume
6
Issue
5
Publish Date
2011
Start Page
332
End Page
345
DOI
10.1002/cmmi.443

Photoacoustic microscopy of tyrosinase reporter gene in vivo.

Photoacoustic tomography is a hybrid modality based on optical absorption excitation and ultrasonic detection. It is sensitive to melanin, one of the primary absorbers in skin. For cells that do not naturally contain melanin, melanin production can be induced by introducing the gene for tyrosinase, the primary enzyme responsible for expression of melanin in melanogenic cells. Optical resolution photoacoustic microscopy was used in the ex vivo study reported here, where the signal from transfected cells increased by more than 10 times over wild-type cells. A subsequent in vivo experiment was conducted to demonstrate the capability of photoacoustic microscopy to spectrally differentiate between tyrosinase-catalyzed melanin and various other absorbers in tissue.

Authors
Krumholz, A; Vanvickle-Chavez, SJ; Yao, J; Fleming, TP; Gillanders, WE; Wang, LV
MLA Citation
Krumholz, A, Vanvickle-Chavez, SJ, Yao, J, Fleming, TP, Gillanders, WE, and Wang, LV. "Photoacoustic microscopy of tyrosinase reporter gene in vivo." Journal of Biomedical Optics 16.8 (August 2011): 080503-. (Letter)
PMID
21895303
Source
epmc
Published In
Journal of Biomedical Optics
Volume
16
Issue
8
Publish Date
2011
Start Page
080503
DOI
10.1117/1.3606568

VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting.

Although our understanding of the molecular regulation of adult neovascularization has advanced tremendously, vascular-targeted therapies for tissue ischemia remain suboptimal. The master regulatory transcription factors of the hypoxia-inducible factor (HIF) family are attractive therapeutic targets because they coordinately up-regulate multiple genes controlling neovascularization. Here, we used an inducible model of epithelial HIF-1 activation, the TetON-HIF-1 mouse, to test the requirement for VEGF in HIF-1 mediated neovascularization. TetON-HIF-1, K14-Cre, and VEGF(flox/flox) alleles were combined to create TetON-HIF-1:VEGF(Δ) mice to activate HIF-1 and its target genes in adult basal keratinocytes in the absence of concomitant VEGF. HIF-1 induction failed to produce neovascularization in TetON-HIF-1:VEGF(Δ) mice despite robust up-regulation of multiple proangiogenic HIF targets, including PlGF, adrenomedullin, angiogenin, and PAI-1. In contrast, endothelial sprouting was preserved, enhanced, and more persistent, consistent with marked reduction in Dll4-Notch-1 signaling. Optical-resolution photoacoustic microscopy, which provides noninvasive, label-free, high resolution, and wide-field vascular imaging, revealed the absence of both capillary expansion and arteriovenous remodeling in serially imaged individual TetON-HIF-1:VEGF(Δ) mice. Impaired TetON-HIF-1:VEGF(Δ) neovascularization could be partially rescued by 12-O-tetradecanoylphorbol-13-acetate skin treatment. These data suggest that therapeutic angiogenesis for ischemic cardiovascular disease may require treatment with both HIF-1 and VEGF.

Authors
Oladipupo, S; Hu, S; Kovalski, J; Yao, J; Santeford, A; Sohn, RE; Shohet, R; Maslov, K; Wang, LV; Arbeit, JM
MLA Citation
Oladipupo, S, Hu, S, Kovalski, J, Yao, J, Santeford, A, Sohn, RE, Shohet, R, Maslov, K, Wang, LV, and Arbeit, JM. "VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting." Proceedings of the National Academy of Sciences of the United States of America 108.32 (August 2011): 13264-13269.
PMID
21784979
Source
epmc
Published In
Proceedings of the National Academy of Sciences of USA
Volume
108
Issue
32
Publish Date
2011
Start Page
13264
End Page
13269
DOI
10.1073/pnas.1101321108

Photoacoustic microscopy of microvascular responses to cortical electrical stimulation.

Advances in the functional imaging of cortical hemodynamics have greatly facilitated the understanding of neurovascular coupling. In this study, label-free optical-resolution photoacoustic microscopy (OR-PAM) was used to monitor microvascular responses to direct electrical stimulations of the mouse somatosensory cortex through a cranial opening. The responses appeared in two forms: vasoconstriction and vasodilatation. The transition between these two forms of response was observed in single vessels by varying the stimulation intensity. Marked correlation was found between the current-dependent responses of two daughter vessels bifurcating from the same parent vessel. Statistical analysis of twenty-seven vessels from three different animals further characterized the spatial-temporal features and the current dependence of the microvascular response. Our results demonstrate that OR-PAM is a valuable tool to study neurovascular coupling at the microscopic level.

Authors
Tsytsarev, V; Hu, S; Yao, J; Maslov, K; Barbour, DL; Wang, LV
MLA Citation
Tsytsarev, V, Hu, S, Yao, J, Maslov, K, Barbour, DL, and Wang, LV. "Photoacoustic microscopy of microvascular responses to cortical electrical stimulation." Journal of biomedical optics 16.7 (July 2011): 076002-.
PMID
21806263
Source
epmc
Published In
Journal of Biomedical Optics
Volume
16
Issue
7
Publish Date
2011
Start Page
076002
DOI
10.1117/1.3594785

Label-free oxygen-metabolic photoacoustic microscopy in vivo.

Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO(2)) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO(2) in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO(2) does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism.

Authors
Yao, J; Maslov, KI; Zhang, Y; Xia, Y; Wang, LV
MLA Citation
Yao, J, Maslov, KI, Zhang, Y, Xia, Y, and Wang, LV. "Label-free oxygen-metabolic photoacoustic microscopy in vivo." Journal of biomedical optics 16.7 (July 2011): 076003-.
PMID
21806264
Source
epmc
Published In
Journal of Biomedical Optics
Volume
16
Issue
7
Publish Date
2011
Start Page
076003
DOI
10.1117/1.3594786

Noninvasive quantification of metabolic rate of oxygen (MRO2) by photoacoustic microscopy

Many diseases, normal decay and physiological functions are closely related to alterations in the metabolic rate of oxygen (MRO 2 ). In this study, we demonstrate that all the parameters for MRO 2 quantification can be simultaneously obtained by optical-resolution photoacoustic microscopy (OR-PAM). MRO 2 of the mouse ear under normothermia (31 °C skin temperature) and controlled systematic hyperthermia (42 °C skin temperature) was studied. As a result of hyperthermia, the MRO 2 increased by 34.1%. The tumor hypermetabolism was also demonstrated by longitudinally monitoring a melanoma growing on a mouse ear. The results show that OR-PAM, as a single noninvasive imaging modality, is well suited for quantitative MRO 2 measurement in microenvironments. © 2011 SPIE.

Authors
Yao, J; Maslov, KI; Wang, LV
MLA Citation
Yao, J, Maslov, KI, and Wang, LV. "Noninvasive quantification of metabolic rate of oxygen (MRO2) by photoacoustic microscopy." May 5, 2011.
Source
scopus
Published In
Proceedings of SPIE
Volume
7899
Publish Date
2011
DOI
10.1117/12.874777

Tyrosinase-catalyzed melanin as a contrast agent for photoacoustic tomography

It is difficult to distinguish between tumor cells and surrounding cells without staining as is done in histology. We developed tyrosinase-catalyzed melanin as a reporter gene for photoacoustic tomography. Tyrosinase is the primary enzyme responsible for the production of melanin and alone is sufficient to produce melanin in non-melanogenic cells. Two cell lines were created: a stably transfected HeLa line and a transiently transfected 293 line. A phantom experiment was performed with the 293 transfected cells 48 hours post transfection and the results compared with oxygenated whole blood, B16 melanoma and 293 control cells. An in vivo experiment was performed using the transfected HeLa cells xenografted into a nude mouse ear, and then imaged. The results show strong contrast for tyrosinase-catalyzed melanin in both the 293 cells in the tube phantom as well as the in vivo result showing melanin in a nude mouse ear. Transfection increased expression in 293 cells 159 fold and image contrast compared to blood by as much as 50 fold. Due to the strong signal obtained at longer wavelengths and the decrease of blood signal at the same wavelengths, tyrosinase catalyzed melanin is a good candidate as a molecular imaging contrast agent for photoacoustic tomography. © 2011 SPIE.

Authors
Krumholz, A; Chavez, S; Yao, J; Fleming, T; Gillanders, WE; Wang, LV
MLA Citation
Krumholz, A, Chavez, S, Yao, J, Fleming, T, Gillanders, WE, and Wang, LV. "Tyrosinase-catalyzed melanin as a contrast agent for photoacoustic tomography." May 5, 2011.
Source
scopus
Published In
Proceedings of SPIE
Volume
7899
Publish Date
2011
DOI
10.1117/12.879110

Effects of calibration factors and intensity dependent non-linearity on functional photoacoustic microscopy

Functional photoacoustic microscopy is a valuable tool in quantifying hemoglobin oxygenation within single vessels. In several functional studies with this tool, quantitative sO 2 measurements were taken both in vitro and in vivo. Although in vitro measurements of sO 2 showed high agreement with expected values from premade samples, in practice, in vivo measurements were less accurate. The reported values of 70%-100% sO2 in the arteries present large deviations from the expected range of 95-100%. Several factors, such as fluence wavelength dependence, optical wavelength range, and transducer central frequency have been suggested and investigated in order to understand these discrepancies. Despite additional knowledge of systematic errors arising from such factors, measuring the absolute value of sO 2 in vivo remains a challenge. All previous studies assumed linear dependence of the photoacoustic signal on absorption and used the linear least squares model. However, several factors, such as wavelength calibration errors, photodiode-wavelength dependence, and intensity dependent non-linearity, all of which may have a significant effect on the final calculation, have not been investigated. Here we evaluate both in vitro and in vivo the effects on sO 2 measurements of photodiode wavelength dependence, laser wavelength accuracy, and intensity dependent absorption of oxygenated and deoxygenated hemoglobin. We show that these factors may contribute significantly to the deviations in sO 2 calculations in vivo. © 2011 SPIE.

Authors
Danielli, A; Yao, J; Krumholz, A; Wang, LV
MLA Citation
Danielli, A, Yao, J, Krumholz, A, and Wang, LV. "Effects of calibration factors and intensity dependent non-linearity on functional photoacoustic microscopy." May 5, 2011.
Source
scopus
Published In
Proceedings of SPIE
Volume
7899
Publish Date
2011
DOI
10.1117/12.875287

Development of real-time photoacoustic microscopy

Photoacoustic tomography detecting ultrasound signals generated from photon absorption provides optical absorption contrast in vivo for structural, functional and molecular imaging. Although photoacoustic tomography technology has grown fast in recent years, real-time photoacoustic imaging with cellular spatial resolution are still strongly demanded. We developed a photoacoustic microscopy which has video-rate imaging capability with cellular spatial resolution. The system consists of a single-element focused ultrasound transducer, a fiber-based light-delivery subsystem, a voice-coil translation stage, a motion controller, and a data acquisition subsystem. A compact cube is employed to split optical and acoustic beams. The mass of the entire scanning photoacoustic probe is less than 40 grams, which minimizes potential vibrations and inertial effects, therefore, makes it capable to scan fast. The imaging system is capable of acquiring 20 cross-sectional (B-scan) images per second over 9 mm, and up to 40 B-scan images per second over 1 mm. Focused laser beams provide a lateral resolution of five microns. Confocal deployment of optical and acoustic focuses provides higher SNR than optical scanning approach. Micron-sized carbon particles flowing in silicone tubing and in vivo blood flows were imaged in video-rate, which demonstrated the capability to image highly dynamic biological processes in vivo with cellular resolution. This real-time high-resolution photoacoustic imaging system provides a promising approach for various in vivo imaging and quantitative studies. © 2011 SPIE.

Authors
Wang, L; Maslov, K; Yao, J; Li, L; Wang, LV
MLA Citation
Wang, L, Maslov, K, Yao, J, Li, L, and Wang, LV. "Development of real-time photoacoustic microscopy." May 5, 2011.
Source
scopus
Published In
Proceedings of SPIE
Volume
7899
Publish Date
2011
DOI
10.1117/12.875415

Conditional HIF-1 induction produces multistage neovascularization with stage-specific sensitivity to VEGFR inhibitors and myeloid cell independence.

Neovascularization is a crucial component of tumor growth and ischemia. Although prior work primarily used disease models, delineation of neovascularization in the absence of disease can reveal intrinsic mechanisms of microvessel regulation amenable to manipulation in illness. We created a conditional model of epithelial HIF-1 induction in adult mice (TetON-HIF-1 mice). Longitudinal photoacoustic microscopy (L-PAM) was coincidentally developed for noninvasive, label-free serial imaging of red blood cell-perfused vasculature in the same mouse for weeks to months. TetON-HIF-1 mice evidenced 3 stages of neovascularization: development, maintenance, and transgene-dependent regression. Regression occurred despite extensive and tight pericyte coverage. L-PAM mapped microvascular architecture and quantified volumetric changes in neocapillary morphogenesis, arteriovenous remodeling, and microvessel regression. Developmental stage endothelial proliferation down-regulation was associated with a DNA damage checkpoint consisting of p53, p21, and endothelial γ-H2AX induction. The neovasculature was temporally responsive to VEGFR2 immuno-blockade, with the developmental stage sensitive, and the maintenance stage resistant, to DC101 treatment. L-PAM analysis also pinpointed microvessels ablated or resistant to VEGFR2 immuno-blockade. HIF-1-recruited myeloid cells did not mediate VEGFR2 inhibitor resistance. Thus, HIF-1 neovascularization in the absence of disease is self-regulated via cell autonomous endothelial checkpoints, and resistant to angiogenesis inhibitors independent of myeloid cells.

Authors
Oladipupo, SS; Hu, S; Santeford, AC; Yao, J; Kovalski, JR; Shohet, RV; Maslov, K; Wang, LV; Arbeit, JM
MLA Citation
Oladipupo, SS, Hu, S, Santeford, AC, Yao, J, Kovalski, JR, Shohet, RV, Maslov, K, Wang, LV, and Arbeit, JM. "Conditional HIF-1 induction produces multistage neovascularization with stage-specific sensitivity to VEGFR inhibitors and myeloid cell independence." Blood 117.15 (April 2011): 4142-4153.
PMID
21307392
Source
epmc
Published In
Blood
Volume
117
Issue
15
Publish Date
2011
Start Page
4142
End Page
4153
DOI
10.1182/blood-2010-09-307538

Photoacoustic microscopy of human teeth

Photoacoustic microscopy (PAM) utilizes short laser pulses to deposit energy into light absorbers and sensitively detects the ultrasonic waves the absorbers generate in response. PAM directly renders a three-dimensional spatial distribution of sub-surface optical absorbers. Unlike other optical imaging technologies, PAM features label-free optical absorption contrast and excellent imaging depths. Standard dental imaging instruments are limited to X-ray and CCD cameras. Subsurface optical dental imaging is difficult due to the highly-scattering enamel and dentin tissue. Thus, very few imaging methods can detect dental decay or diagnose dental pulp, which is the innermost part of the tooth, containing the nerves, blood vessels, and other cells. Here, we conducted a feasibility study on imaging dental decay and dental pulp with PAM. Our results showed that PAM is sensitive to the color change associated with dental decay. Although the relative PA signal distribution may be affected by surface contours and subsurface reflections from deeper dental tissue, monitoring changes in the PA signals (at the same site) over time is necessary to identify the progress of dental decay. Our results also showed that deep-imaging, near-infrared (NIR) PAM can sensitively image blood in the dental pulp of an in vitro tooth. In conclusion, PAM is a promising tool for imaging both dental decay and dental pulp. © 2011 SPIE.

Authors
Rao, B; Cai, X; Christopher, F; Yao, J; Li, L; Duong, S; Liaw, LH; Holtzman, J; Wilder-Smith, P; Wang, LV
MLA Citation
Rao, B, Cai, X, Christopher, F, Yao, J, Li, L, Duong, S, Liaw, LH, Holtzman, J, Wilder-Smith, P, and Wang, LV. "Photoacoustic microscopy of human teeth." March 31, 2011.
Source
scopus
Published In
Proceedings of SPIE
Volume
7884
Publish Date
2011
DOI
10.1117/12.874070

Fast voice-coil scanning optical-resolution photoacoustic microscopy.

We developed a photoacoustic imaging system that has real-time imaging capability with optical resolution. The imaging system is capable of scanning at 20 Hz over a 9 mm range and up to 40 Hz over a 1 mm scanning range. A focused laser beam provides a lateral resolution of 3.4 μm as measured in an optically nonscattering medium. Flows of micrometer-sized carbon particles or whole blood in a silicone tube and individual red blood cells (RBCs) in mouse ear capillaries were also imaged in real time, demonstrating the capability to image highly dynamic processes in vivo at a micrometer-scale resolution.

Authors
Wang, L; Maslov, K; Yao, J; Rao, B; Wang, LV
MLA Citation
Wang, L, Maslov, K, Yao, J, Rao, B, and Wang, LV. "Fast voice-coil scanning optical-resolution photoacoustic microscopy." Optics letters 36.2 (January 2011): 139-141.
PMID
21263479
Source
epmc
Published In
Optics Letters
Volume
36
Issue
2
Publish Date
2011
Start Page
139
End Page
141
DOI
10.1364/ol.36.000139

In vivo photoacoustic mapping of lymphatic systems with plasmon-resonant nanostars.

Plasmon-resonant nanostars (NSTs) provide excellent contrast enhancement for photoacoustic tomography. The high photoacoustic sensitivity of NSTs at near-infrared wavelengths enable their in vivo detection in rat sentinel lymph nodes and vessels, with direct application toward lymphangiography.

Authors
Kim, C; Song, H-M; Cai, X; Yao, J; Wei, A; Wang, LV
MLA Citation
Kim, C, Song, H-M, Cai, X, Yao, J, Wei, A, and Wang, LV. "In vivo photoacoustic mapping of lymphatic systems with plasmon-resonant nanostars." Journal of materials chemistry 21.9 (January 2011): 2841-2844.
PMID
21660122
Source
epmc
Published In
Journal of Materials Chemistry
Volume
21
Issue
9
Publish Date
2011
Start Page
2841
End Page
2844
DOI
10.1039/c0jm04194g

Photoacoustic microscopy using Evans Blue dye as a contrast agent

Complete and continuous imaging of microvascular networks is crucial for a wide variety of biomedical applications. Photoacoustic tomography can provide high resolution microvascular imaging using hemoglobin within red blood cells (RBC) as an endogenous contrast agent. However, intermittent RBC flow in capillaries results in discontinuous and fragmentary capillary images. To overcome this problem, we used Evans Blue (EB) dye as a contrast agent for in vivo photoacoustic imaging. EB has strong optical absorption at 610 nm and distributes uniformly in the blood stream by chemically binding to albumin. By intravenous injection of EB (6%, 200 μL), complete and continuous microvascular networks-especially capillaries-of the ears of nude mice were imaged. The diffusion of EB (3%, 100 μL) leaving the blood stream was monitored for 2 hours. At lower administration dose of EB (3%, 50 μL), the clearance of the EB-albumin complex was imaged for 10 days and quantitatively investigated using a two-compartment model. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Authors
Yao, J; Maslov, KI; Hu, S; Wang, LV
MLA Citation
Yao, J, Maslov, KI, Hu, S, and Wang, LV. "Photoacoustic microscopy using Evans Blue dye as a contrast agent." May 3, 2010.
Source
scopus
Published In
Proceedings of SPIE
Volume
7564
Publish Date
2010
DOI
10.1117/12.840684

Invasive and transcranial photoacoustic imaging of the vascular response to brain electrical stimulation

Advances in the brain functional imaging greatly facilitated the understanding of neurovascular coupling. For monitoring of the microvascular response to the brain electrical stimulation in vivo we used optical-resolution photoacoustic microscopy (OR-PAM) through the cranial openings as well as transcranially. Both types of the vascular response, vasoconstriction and vasodilatation, were clearly observed with good spatial and temporal resolution. Obtained results confirm one of the primary points of the neurovascular coupling theory that blood vessels could present vasoconstriction or vasodilatation in response to electrical stimulation, depending on the balance between inhibition and excitation of the different parts of the elements of the neurovascular coupling system. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Authors
Tsytsarev, V; Yao, J; Hu, S; Li, L; Favazza, CP; Maslov, KI; Wang, LV
MLA Citation
Tsytsarev, V, Yao, J, Hu, S, Li, L, Favazza, CP, Maslov, KI, and Wang, LV. "Invasive and transcranial photoacoustic imaging of the vascular response to brain electrical stimulation." May 3, 2010.
Source
scopus
Published In
Proceedings of SPIE
Volume
7564
Publish Date
2010
DOI
10.1117/12.840290

Transverse flow measurement using photoacoustic Doppler bandwidth broadening: Phantom and in vivo studies

In photoacoustic (PA) imaging of microvascular networks, the transverse component of the blood flow that is perpendicular to the acoustic probing beam is usually dominant. We propose a new method to measure the transverse flow, based on the Doppler bandwidth broadening. The bandwidth broadening is inversely proportional to the transit time spent by the absorbers passing through the focus. Because the photoacoustic signal in one A-scan has a wide band, multiple successive A-scans are used to estimate the relatively small signal variance. Then the bandwidth broadening can be calculated from the standard derivation of the Doppler spectrum. By exploiting the pulse excitation and bidirectional raster motor scanning, threedimensional structural and flow information can be obtained simultaneously. From a flow of a suspension of carbon particles (diameter: 6 μm), transverse flow speeds from 0 to 2.5 mm/s were measured using optical-resolution photoacoustic microscopy. The bandwidth broadening at each speed was in good agreement with the theoretical prediction. The blood flow in a mouse brain was also imaged. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Authors
Yao, J; Maslov, KI; Wang, LV
MLA Citation
Yao, J, Maslov, KI, and Wang, LV. "Transverse flow measurement using photoacoustic Doppler bandwidth broadening: Phantom and in vivo studies." May 3, 2010.
Source
scopus
Published In
Proceedings of SPIE
Volume
7564
Publish Date
2010
DOI
10.1117/12.840676

Optical-resolution photoacoustic microscopy of angiogenesis in a transgenic mouse model

A major obstacle in studying angiogenesis is the inability to noninvasively image neovascular development in an individual animal. We applied optical-resolution photoacoustic microscopy (OR-PAM) to determine the kinetics of hypoxia-inducible factor-1 (HIF-1)-mediated angiogenesis in a transgenic mouse model. During continuous 30-day activation of HIF-1α, we used OR-PAM to monitor alterations in microvasculature in transgenic mice compared to nontransgenic mice. OR-PAM has demonstrated the potential to precisely monitor antiangiogenic therapy of human cancers, allowing for rapid determinations of therapeutic efficacy or resistance. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Authors
Hu, S; Oladipupo, S; Yao, J; Santeford, AC; Maslov, K; Kovalski, J; Arbeit, JM; Wang, LV
MLA Citation
Hu, S, Oladipupo, S, Yao, J, Santeford, AC, Maslov, K, Kovalski, J, Arbeit, JM, and Wang, LV. "Optical-resolution photoacoustic microscopy of angiogenesis in a transgenic mouse model." May 3, 2010.
Source
scopus
Published In
Proceedings of SPIE
Volume
7564
Publish Date
2010
DOI
10.1117/12.841177

In vivo photoacoustic imaging of transverse blood flow by using Doppler broadening of bandwidth.

A method is proposed to measure transverse blood flow by using photoacoustic Doppler broadening of bandwidth. By measuring bovine blood flowing through a plastic tube, the linear dependence of the broadening on the flow speed was validated. The blood flow of the microvasculature in a mouse ear and a chicken embryo (stage 16) was also studied.

Authors
Yao, J; Maslov, KI; Shi, Y; Taber, LA; Wang, LV
MLA Citation
Yao, J, Maslov, KI, Shi, Y, Taber, LA, and Wang, LV. "In vivo photoacoustic imaging of transverse blood flow by using Doppler broadening of bandwidth." Optics letters 35.9 (May 2010): 1419-1421.
PMID
20436589
Source
epmc
Published In
Optics Letters
Volume
35
Issue
9
Publish Date
2010
Start Page
1419
End Page
1421
DOI
10.1364/ol.35.001419

Three-Dimensional Reconstruction for Fluorescence Tomography Using Cylinder Phantoms

Authors
SONG, X-L; HU, G; HU, G; BAI, J
MLA Citation
SONG, X-L, HU, G, HU, G, and BAI, J. "Three-Dimensional Reconstruction for Fluorescence Tomography Using Cylinder Phantoms." Journal of Software 20.5 (March 10, 2010): 1089-1095.
Source
crossref
Published In
Ruan Jian Xue Bao/Journal of Software
Volume
20
Issue
5
Publish Date
2010
Start Page
1089
End Page
1095
DOI
10.3724/SP.J.1001.2009.03560

Transverse flow imaging based on photoacoustic Doppler bandwidth broadening.

We propose a new method to measure transverse flow velocity based on photoacoustic Doppler bandwidth broadening, which is determined by the geometry of the probe-beam and the velocity of the transverse flow. By exploiting pulsed laser excitation and raster motor scanning, three-dimensional structure and flow velocity can be imaged simultaneously. In addition, the flow direction can be determined with bidirectional scanning. In a flowing suspension of red-dyed microspheres (diameter: 6 microm), transverse flow speeds ranging from 0 to 2.5 mms as well as flow direction were measured. A cross-sectional flow image was also obtained with the tube laid in a zigzag pattern.

Authors
Yao, J; Wang, LV
MLA Citation
Yao, J, and Wang, LV. "Transverse flow imaging based on photoacoustic Doppler bandwidth broadening." Journal of Biomedical Optics 15.2 (March 2010): 021304-.
PMID
20459226
Source
epmc
Published In
Journal of Biomedical Optics
Volume
15
Issue
2
Publish Date
2010
Start Page
021304
DOI
10.1117/1.3339953

Evans blue dye-enhanced capillary-resolution photoacoustic microscopy in vivo.

Complete and continuous imaging of microvascular networks is crucial for a wide variety of biomedical applications. Photoacoustic tomography can provide high resolution microvascular imaging using hemoglobin within red blood cells (RBCs) as an endogenic contrast agent. However, intermittent RBC flow in capillaries results in discontinuous and fragmentary capillary images. To overcome this problem, we use Evans blue (EB) dye as a contrast agent for in vivo photoacoustic imaging. EB has strong optical absorption and distributes uniformly in the blood stream by chemically binding to albumin. With the help of EB, complete and continuous microvascular networks--especially capillaries--are imaged. The diffusion dynamics of EB leaving the blood stream and the clearance dynamics of the EB-albumin complex are also quantitatively investigated.

Authors
Yao, J; Maslov, K; Hu, S; Wang, LV
MLA Citation
Yao, J, Maslov, K, Hu, S, and Wang, LV. "Evans blue dye-enhanced capillary-resolution photoacoustic microscopy in vivo." Journal of biomedical optics 14.5 (September 2009): 054049-.
PMID
19895150
Source
epmc
Published In
Journal of Biomedical Optics
Volume
14
Issue
5
Publish Date
2009
Start Page
054049
DOI
10.1117/1.3251044

Modeling and validation of light propagation in free-space for non-contact near-infrared fluorescent tomography

Light propagation from the object boundary to detector was presented for non-contact near infrared fluorescent molecular tomography (FMT). Based on the work of Jorge Ripoll et al, perspective projection effect of lens was considered. The formula for light intensity transport in free-space was simplified. The relationship of the light intensity distribution on object boundary and the value obtained by CCD camera was established. Phantom experiment results confirm that this model is an efficient approach for non-contact near-infrared fluorescent molecular tomography.

Authors
Yao, JJ; Hu, G; Bai, J
MLA Citation
Yao, JJ, Hu, G, and Bai, J. "Modeling and validation of light propagation in free-space for non-contact near-infrared fluorescent tomography." Hongwai Yu Haomibo Xuebao/Journal of Infrared and Millimeter Waves 27.5 (October 1, 2008).
Source
scopus
Published In
Hongwai Yu Haomibo Xuebao/Journal of Infrared and Millimeter Waves
Volume
27
Issue
5
Publish Date
2008

Fluorescent optical imaging of small animals using filtered back-projection 3D surface reconstruction method

The CCD-based non-contact fluorescent optical imaging has got a promising progress in recent years. This imaging modality needs the 3D surface of the small animal, which is used for the forward model and inverse reconstruction. We propose a new 3D surface reconstruction method based on the back projection method using white/black images. After taking the surface images by CCD, the transverse reconstruction is completed using filter back-projection method. Based on the data of the edges and calibration operation, we reconstruct the 3D surface of the animals. To validate the accuracy of the optical method, we compared the external shape data of mouse phantom to that from the micro-CT system. Some in vivo fluorescence imaging results are also presented in this paper © 2008 IEEE.

Authors
Hu, G; Yao, J; Li, H; Bai, J
MLA Citation
Hu, G, Yao, J, Li, H, and Bai, J. "Fluorescent optical imaging of small animals using filtered back-projection 3D surface reconstruction method." September 18, 2008.
Source
scopus
Published In
BioMedical Engineering and Informatics: New Development and the Future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics, BMEI 2008
Volume
2
Publish Date
2008
Start Page
76
End Page
80
DOI
10.1109/BMEI.2008.61

A 3D-surface torso reconstruction method used in fluorescence molecular tomography of small animals

Objective: The CCD-based non-contact fluorescencemolecular tomography has got a rapid progress in recent years. This imaging modality needs to acquire 3D-surface of the animal imaged, which is used as the forward model in the fluorescence concentration reconstruction. Methods: We proposed a new 3D-surface reconstruction method based on the back-projection method under the white light condition. After taking the surface pictures by CCD, the slice images were reconstructed using filter back- projection method, then the edge curve of each slice was extracted, and based on the data of the edges and calibration operation, we reconstructed the 3D-surface of the animal imaged. Results: The results of both phantom simulation and animal experiment showed that the method properly reconstructed the 3D-surface of trunk of small animals. Conclusions: Compared with other methods, this method is simple and fast. Furthermore, the proposed method enables the surface imaging to be inserted into the working process of the whole FMT system without interruption.

Authors
Yao, JJ; Hu, G; Yue, SH; Bai, J
MLA Citation
Yao, JJ, Hu, G, Yue, SH, and Bai, J. "A 3D-surface torso reconstruction method used in fluorescence molecular tomography of small animals." Chinese Journal of Biomedical Engineering 27.3 (June 1, 2008): 360-365.
Source
scopus
Published In
Zhongguo Shengwu Yixue Gongcheng Xuebao/Chinese Journal of Biomedical Engineering
Volume
27
Issue
3
Publish Date
2008
Start Page
360
End Page
365

Full-angle optical imaging of near-infrared fluorescent probes implanted in small animals

Authors
Hu, G; Yao, J; Bai, J
MLA Citation
Hu, G, Yao, J, and Bai, J. "Full-angle optical imaging of near-infrared fluorescent probes implanted in small animals." Progress in Natural Science 18.6 (June 2008): 707-711.
Source
crossref
Published In
Progress in Natural Science (Elsevier)
Volume
18
Issue
6
Publish Date
2008
Start Page
707
End Page
711
DOI
10.1016/j.pnsc.2007.11.021
Show More

Research Areas:

  • Acoustic imaging
  • Cancer--Imaging
  • Imaging
  • Photoacoustic Techniques