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Zhang, Xiaofeng

Overview:

Xiaofeng “Steve” Zhang graduated from Tsinghua University (China) in Chemical Engineering (B.E. in 1997), and received his graduate degrees from University of Illinois at Urbana-Champaign in Electrical Engineering (M.S. in 2003 and Ph.D. in 2005). He studies the interaction of light with biological tissue, with which to noninvasively probe various biomedical phenomena in vivo, and the means to tomographically visualize such phenomena.

Positions:

Assistant Professor of Radiology

Radiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2005

Ph.D. — University of Illinois -- Urbana-Champaign

Grants:

Resolution Limits for Fluorescence Tomographic Molecular Imaging

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 15, 2010
End Date
August 31, 2013

Small Animal Imaging Resource Program

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Research Associate
Start Date
August 30, 2001
End Date
February 29, 2012

Publications:

Noninvasive measurement of tissue blood oxygenation with Cerenkov imaging during therapeutic radiation delivery.

Tumor tissue oxygenation significantly affects the outcome of radiotherapy. Real-time monitoring of tumor hypoxia is highly desirable for effective radiotherapy, and is the basis for improved treatment because hypoxic tumor cells are more resistant to radiation damage than fully oxygenated cells. We propose to use Cerenkov imaging to monitor tumor hypoxia by means of tissue blood oxygenation without the need for any exogenous contrast agent. Using a rodent hypoxia model, we demonstrate that Cerenkov imaging can be used as a noninvasive and noncontact method to measure tissue blood oxygenation level during radiation delivery. The data from Cerenkov imaging were validated using near infrared spectrometry methods. The results demonstrate the feasibility of using Cerenkov imaging to monitor tumor hypoxia during therapeutic radiation delivery.

Authors
Zhang, X; Lam, SK; Palmer, G; Das, S; Oldham, M; Dewhirst, M
MLA Citation
Zhang, X, Lam, SK, Palmer, G, Das, S, Oldham, M, and Dewhirst, M. "Noninvasive measurement of tissue blood oxygenation with Cerenkov imaging during therapeutic radiation delivery." Optics letters 42.16 (August 2017): 3101-3104.
Website
http://hdl.handle.net/10161/15411
PMID
28809883
Source
epmc
Published In
Optics Letters
Volume
42
Issue
16
Publish Date
2017
Start Page
3101
End Page
3104
DOI
10.1364/ol.42.003101

Time-Resolved Synchronous Fluorescence for Biomedical Diagnosis.

This article presents our most recent advances in synchronous fluorescence (SF) methodology for biomedical diagnostics. The SF method is characterized by simultaneously scanning both the excitation and emission wavelengths while keeping a constant wavelength interval between them. Compared to conventional fluorescence spectroscopy, the SF method simplifies the emission spectrum while enabling greater selectivity, and has been successfully used to detect subtle differences in the fluorescence emission signatures of biochemical species in cells and tissues. The SF method can be used in imaging to analyze dysplastic cells in vitro and tissue in vivo. Based on the SF method, here we demonstrate the feasibility of a time-resolved synchronous fluorescence (TRSF) method, which incorporates the intrinsic fluorescent decay characteristics of the fluorophores. Our prototype TRSF system has clearly shown its advantage in spectro-temporal separation of the fluorophores that were otherwise difficult to spectrally separate in SF spectroscopy. We envision that our previously-tested SF imaging and the newly-developed TRSF methods will combine their proven diagnostic potentials in cancer diagnosis to further improve the efficacy of SF-based biomedical diagnostics.

Authors
Zhang, X; Fales, A; Vo-Dinh, T
MLA Citation
Zhang, X, Fales, A, and Vo-Dinh, T. "Time-Resolved Synchronous Fluorescence for Biomedical Diagnosis." Sensors (Basel, Switzerland) 15.9 (January 2015): 21746-21759.
Website
http://hdl.handle.net/10161/11299
PMID
26404289
Source
epmc
Published In
Sensors (Basel, Switzerland)
Volume
15
Issue
9
Publish Date
2015
Start Page
21746
End Page
21759
DOI
10.3390/s150921746

SU-E-T-521: Feasibility Study of a Rotational Step-And-Shoot IMRT Treatment Planning Approach.

Rotational step-and-shot IMRT (r-IMRT) could improve delivery efficiency with good dose conformity, especially if it can leverage the burst mode of the accelerator where radiation is turned on/off momentarily while the gantry rotates continuously. The challenge for the r-IMRT planning is to minimize the number of beams to achieve a fast and smooth rotational delivery.Treatment plans for r-IMRT were created using an in-house treatment planning system. To generate the plan using a very few beams, gantry angle was optimized by weighting the beam monitoring unit (MU), and beam shape optimization was a combination of column search with k-means clustering. A prostate case and a head and neck case were planned using r-IMRT. The dosimetry is compared to s-IMRT planned with Varian Eclipse treatment planning system.With the same PTV dose coverage D95=100%, the r-IMRT plans shows comparable sparing as the s-IMRT plans in the prostate for the rectum D10cc and the bladder Dmean, and in the head and neck for the spinal cord Dmax, the brain stem Dmax, the left/right parotid Dmean, the larynx Dmean, and the mandible Dmean. Both plans meet the established institutional clinical dosimetric criteria. The r-IMRT plan uses 19 beam/405 MU for the prostate, and 68 beam/880 MU for the head and neck, while the s-IMRT uses 7 beam/724 MU and 9 beam/1812 MU, respectively. Compared to the corresponding s-IMRT, r-IMRT has a reduction of MUs of 44% for the prostate case and 41% for the head and neck case.We have demonstrated the feasibility of a rotational step & shoot IMRT treatment planning approach that significantly shortens the conventional IMRT treatment beam-on time without degrading the dose comformity.

Authors
Zhu, X; Chang, S; Cullip, T; Yuan, L; Lian, J; Zhang, X; Tang, X; Tracton, G; Dooley, J
MLA Citation
Zhu, X, Chang, S, Cullip, T, Yuan, L, Lian, J, Zhang, X, Tang, X, Tracton, G, and Dooley, J. "SU-E-T-521: Feasibility Study of a Rotational Step-And-Shoot IMRT Treatment Planning Approach." Medical physics 41.6 (June 2014): 347-.
PMID
28037348
Source
epmc
Published In
Medical physics
Volume
41
Issue
6
Publish Date
2014
Start Page
347
DOI
10.1118/1.4888854

Instrumentation in Diffuse Optical Imaging.

Diffuse optical imaging is highly versatile and has a very broad range of applications in biology and medicine. It covers diffuse optical tomography, fluorescence diffuse optical tomography, bioluminescence, and a number of other new imaging methods. These methods of diffuse optical imaging have diversified instrument configurations but share the same core physical principle - light propagation in highly diffusive media, i.e., the biological tissue. In this review, the author summarizes the latest development in instrumentation and methodology available to diffuse optical imaging in terms of system architecture, light source, photo-detection, spectral separation, signal modulation, and lastly imaging contrast.

Authors
Zhang, X
MLA Citation
Zhang, X. "Instrumentation in Diffuse Optical Imaging." Photonics 1.1 (March 2014): 9-32.
Website
http://hdl.handle.net/10161/11300
PMID
24860804
Source
epmc
Published In
Photonics
Volume
1
Issue
1
Publish Date
2014
Start Page
9
End Page
32
DOI
10.3390/photonics1010009

Super-resolution method for arbitrary retrospective sampling in fluorescence tomography with raster scanning photodetectors

Dense spatial sampling is required in high-resolution optical imaging and many other biomedical optical imaging methods, such as diffuse optical imaging. Arrayed photodetectors, in particular charge coupled device cameras are commonly used mainly because of their high pixel count. Nonetheless, discrete-element photodetectors, such as photomultiplier tubes, are often desirable in many performance-demanding imaging applications. However, utilization of the discrete-element photodetectors typically requires raster scan to achieve arbitrary retrospective sampling with high density. Care must be taken in using the relatively large sensitive areas of discrete-element photodetectors to densely sample the image plane. In addition, off-line data analysis and image reconstruction often require full-field sampling. Pixel-by-pixel scanning is not only slow but also unnecessary in diffusion-limited imaging. We propose a superresolution method that can recover the finer features of an image sampled with a coarse-scale sensor. This generalpurpose method was established on the spatial transfer function of the photodetector-lens system, and achieved superresolution by inversion of this linear transfer function. Regularized optimization algorithms were used to achieve optimized deconvolution. Compared to the uncorrected blurred image, the proposed super-resolution method significantly improved image quality in terms of resolution and quantitation. Using this reconstruction method, the acquisition speed with a scanning photodetector can be dramatically improved without significantly sacrificing sampling density or flexibility. © 2013 Copyright SPIE.

Authors
Zhang, X
MLA Citation
Zhang, X. "Super-resolution method for arbitrary retrospective sampling in fluorescence tomography with raster scanning photodetectors." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8572 (2013).
Website
http://hdl.handle.net/10161/13280
PMID
24224075
Source
scival
Published In
Proceedings of SPIE
Volume
8572
Publish Date
2013
DOI
10.1117/12.2001518

Detectability of absorption and reduced scattering coefficients in frequency-domain measurements using a realistic head phantom.

Detection limits of the changes in absorption and reduced scattering coefficients were investigated using a frequency-domain near-infrared system in a realistic head phantom. The results were quantified in terms of the maximum detectable depth for different activation volumes in the range of 0.8-20 microliters. The non-linear relation between the maximum detectable depth and the magnitude of changes in the absorption coefficient conform well with the Born approximation to the diffusion equation. The minimal detectable changes in the reduced scattering coefficient measured in terms of the phase signal were found to be approximately twice as large as that of the absorption coefficient using the AC signal for the same volume and at the same depth. The phase delay, which can be used to quantify the fast neuronal optical response in the human brain, showed a linear dependence on the reciprocal of the reduced scattering coefficient, as predicted by the Rytov approximation.

Authors
Zhang, X; Webb, A
MLA Citation
Zhang, X, and Webb, A. "Detectability of absorption and reduced scattering coefficients in frequency-domain measurements using a realistic head phantom. (Published online)" Sensors (Basel) 13.1 (December 24, 2012): 152-164.
Website
http://hdl.handle.net/10161/11301
PMID
23262479
Source
pubmed
Published In
Sensors (Basel, Switzerland)
Volume
13
Issue
1
Publish Date
2012
Start Page
152
End Page
164
DOI
10.3390/s130100152

Construction of the Jacobian matrix for fluorescence diffuse optical tomography using a perturbation Monte Carlo method

Image formation in fluorescence diffuse optical tomography is critically dependent on construction of the Jacobian matrix. For clinical and preclinical applications, because of the highly heterogeneous characteristics of the medium, Monte Carlo methods are frequently adopted to construct the Jacobian. Conventional adjoint Monte Carlo method typically compute the Jacobian by multiplying the photon density fields radiated from the source at the excitation wavelength and from the detector at the emission wavelength. Nonetheless, this approach assumes that the source and the detector in Green's function are reciprocal, which is invalid in general. This assumption is particularly questionable in small animal imaging, where the mean free path length of photons is typically only one order of magnitude smaller than the representative dimension of the medium. We propose a new method that does not rely on the reciprocity of the source and the detector by tracing photon propagation entirely from the source to the detector. This method relies on the perturbation Monte Carlo theory to account for the differences in optical properties of the medium at the excitation and the emission wavelengths. Compared to the adjoint methods, the proposed method is more valid in reflecting the physical process of photon transport in diffusive media and is more efficient in constructing the Jacobian matrix for densely sampled configurations. © 2012 SPIE.

Authors
Zhang, X
MLA Citation
Zhang, X. "Construction of the Jacobian matrix for fluorescence diffuse optical tomography using a perturbation Monte Carlo method." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8216 (2012).
Website
http://hdl.handle.net/10161/13279
PMID
24027610
Source
scival
Published In
Proceedings of SPIE
Volume
8216
Publish Date
2012
DOI
10.1117/12.906439

High-resolution reconstruction of fluorescent inclusions in mouse thorax using anatomically guided sampling and parallel Monte Carlo computing.

We present a method for high-resolution reconstruction of fluorescent images of the mouse thorax. It features an anatomically guided sampling method to retrospectively eliminate problematic data and a parallel Monte Carlo software package to compute the Jacobian matrix for the inverse problem. The proposed method was capable of resolving microliter-sized femtomole amount of quantum dot inclusions closely located in the middle of the mouse thorax. The reconstruction was verified against co-registered micro-CT data. Using the proposed method, the new system achieved significantly higher resolution and sensitivity compared to our previous system consisting of the same hardware. This method can be applied to any system utilizing similar imaging principles to improve imaging performance.

Authors
Zhang, X; Badea, C; Hood, G; Wetzel, A; Qi, Y; Stiles, J; Johnson, GA
MLA Citation
Zhang, X, Badea, C, Hood, G, Wetzel, A, Qi, Y, Stiles, J, and Johnson, GA. "High-resolution reconstruction of fluorescent inclusions in mouse thorax using anatomically guided sampling and parallel Monte Carlo computing." Biomed Opt Express 2.9 (September 1, 2011): 2449-2460.
Website
http://hdl.handle.net/10161/11254
PMID
21991539
Source
pubmed
Published In
Biomedical Optics Express
Volume
2
Issue
9
Publish Date
2011
Start Page
2449
End Page
2460
DOI
10.1364/BOE.2.002449

Highly efficient detection in fluorescence tomography of quantum dots using time-gated acquisition and ultrafast pulsed laser.

Quantum dots (QDs) are widely used in fluorescence tomography due to its unique advantages. Despite the very high quantum efficiency of the QDs, low fluorescent signal and autofluorescence are the most fundamental limitations in optical data acquisition. These limitations are particularly detrimental to image reconstruction for animal imaging, e.g., free-space in vivo fluorescence tomography. In animals studies, fluorescent emission from exogenous fluorescent probes (e.g. QDs) cannot be effectively differentiated from endogenous broad-spectral substances (mostly proteins) using optical filters. In addition, a barrow-band fluorescent filter blocks the majority of the fluorescent light and thus makes signal acquisition very inefficient. We made use of the long fluorescent lifetime of the QDs to reject the optical signal due to the excitation light pulse, and therefore eliminated the need for a fluorescent filter during acquisition. Fluorescent emission from the QDs was excited with an ultrafast pulsed laser, and was detected using a time-gated image intensifier. A tissue-simulating imaging phantom was used to validate the proposed method. Compared to the standard acquisition method that uses a narrow-band fluorescent filter, the proposed method is significantly more efficient in data acquisition (by a factor of >10 in terms of fluorescent signal intensity) and demonstrated reduction in autofluorescence. No additional imaging artifact was observed in the tomographic reconstruction.

Authors
Zhang, X; Badea, CT
MLA Citation
Zhang, X, and Badea, CT. "Highly efficient detection in fluorescence tomography of quantum dots using time-gated acquisition and ultrafast pulsed laser." Proc SPIE Int Soc Opt Eng 7896 (January 23, 2011).
Website
http://hdl.handle.net/10161/13278
PMID
21373380
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7896
Publish Date
2011
DOI
10.1117/12.875502

Free-space fluorescence tomography with adaptive sampling based on anatomical information from microCT.

Image reconstruction is one of the main challenges for fluorescence tomography. For in vivo experiments on small animals, in particular, the inhomogeneous optical properties and irregular surface of the animal make free-space image reconstruction challenging because of the difficulties in accurately modeling the forward problem and the finite dynamic range of the photodetector. These two factors are fundamentally limited by the currently available forward models and photonic technologies. Nonetheless, both limitations can be significantly eased using a signal processing approach. We have recently constructed a free-space panoramic fluorescence diffuse optical tomography system to take advantage of co-registered microCT data acquired from the same animal. In this article, we present a data processing strategy that adaptively selects the optical sampling points in the raw 2-D fluorescent CCD images. Specifically, the general sampling area and sampling density are initially specified to create a set of potential sampling points sufficient to cover the region of interest. Based on 3-D anatomical information from the microCT and the fluorescent CCD images, data points are excluded from the set when they are located in an area where either the forward model is known to be problematic (e.g., large wrinkles on the skin) or where the signal is unreliable (e.g., saturated or low signal-to-noise ratio). Parallel Monte Carlo software was implemented to compute the sensitivity function for image reconstruction. Animal experiments were conducted on a mouse cadaver with an artificial fluorescent inclusion. Compared to our previous results using a finite element method, the newly developed parallel Monte Carlo software and the adaptive sampling strategy produced favorable reconstruction results.

Authors
Zhang, X; Badea, CT; Hood, G; Wetzel, AW; Stiles, JR; Johnson, GA
MLA Citation
Zhang, X, Badea, CT, Hood, G, Wetzel, AW, Stiles, JR, and Johnson, GA. "Free-space fluorescence tomography with adaptive sampling based on anatomical information from microCT." United States. 2010.
PMID
21743784
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7757
Issue
775706
Publish Date
2010
DOI
10.1117/12.841891

Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy.

We present a 3-D image reconstruction method for free-space fluorescence tomography of mice using hybrid anatomical prior information. Specifically, we use an optically reconstructed surface of the experimental animal and a digital mouse atlas to approximate the anatomy of the animal as structural priors to assist image reconstruction. Experiments are carried out on a cadaver of a nude mouse with a fluorescent inclusion (2.4-mm-diam cylinder) implanted in the chest cavity. Tomographic fluorescence images are reconstructed using an iterative algorithm based on a finite element method. Coregistration of the fluorescence reconstruction and micro-CT (computed tomography) data acquired afterward show good localization accuracy (localization error 1.2+/-0.6 mm). Using the optically reconstructed surface, but without the atlas anatomy, image reconstruction fails to show the fluorescent inclusion correctly. The method demonstrates the utility of anatomical priors in support of free-space fluorescence tomography.

Authors
Zhang, X; Badea, CT; Johnson, GA
MLA Citation
Zhang, X, Badea, CT, and Johnson, GA. "Three-dimensional reconstruction in free-space whole-body fluorescence tomography of mice using optically reconstructed surface and atlas anatomy." J Biomed Opt 14.6 (November 2009): 064010-.
PMID
20059248
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
14
Issue
6
Publish Date
2009
Start Page
064010
DOI
10.1117/1.3258836

Effects of sampling strategy on image quality in noncontact panoramic fluorescence diffuse optical tomography for small animal imaging.

Fluorescence diffuse optical tomography is an emerging technology for molecular imaging with recent technological advances in biomarkers and photonics. The introduction of noncontact imaging methods enables very large-scale data acquisition that is orders of magnitude larger than that from earlier systems. In this study, the effects of sampling strategy on image quality were investigated using an imaging phantom mimicking small animals and further analyzed using singular value analysis (SVA). The sampling strategy was represented in terms of a number of key acquisition parameters, namely the numbers of sources, detectors, and imaging angles. A number of metrics were defined to quantitatively evaluate image quality. The effects of acquisition parameters on image quality were subsequently studied by varying each of the parameters within a reasonable range while maintaining the other parameters constant, a method analogue to partial derivative in mathematical analysis. It was found that image quality improves at a much slower rate if the acquisition parameters are above certain critical values (approximately 5 sources, approximately 15 detectors, and approximately 20 angles for our system). These critical values remain virtually the same even if other acquisition parameters are doubled. It was also found that increasing different acquisition parameters improves image quality with different efficiencies in terms of the number of measurements: for a system characterized by a smaller threshold in SVA (less than 10(-5) in our study), the number of sources is the most efficient, followed by the number of detectors and subsequently the number of imaging angles. However, for systems characterized by a larger threshold, the numbers of sources and angles are equally more efficient than the number of detectors.

Authors
Zhang, X; Badea, C
MLA Citation
Zhang, X, and Badea, C. "Effects of sampling strategy on image quality in noncontact panoramic fluorescence diffuse optical tomography for small animal imaging." Opt Express 17.7 (March 30, 2009): 5125-5138.
PMID
19333276
Source
pubmed
Published In
Optics express
Volume
17
Issue
7
Publish Date
2009
Start Page
5125
End Page
5138

Development of a noncontact 3-D fluorescence tomography system for small animal in vivo imaging.

Fluorescence imaging is an important tool for tracking molecular-targeting probes in preclinical studies. It offers high sensitivity, but nonetheless low spatial resolution compared to other leading imaging methods such CT and MRI. We demonstrate our methodological development in small animal in vivo whole-body imaging using fluorescence tomography. We have implemented a noncontact fluid-free fluorescence diffuse optical tomography system that uses a raster-scanned continuous-wave diode laser as the light source and an intensified CCD camera as the photodetector. The specimen is positioned on a motorized rotation stage. Laser scanning, data acquisition, and stage rotation are controlled via LabVIEW applications. The forward problem in the heterogeneous medium is based on a normalized Born method, and the sensitivity function is determined using a Monte Carlo method. The inverse problem (image reconstruction) is performed using a regularized iterative algorithm, in which the cost function is defined as a weighted sum of the L-2 norms of the solution image, the residual error, and the image gradient. The relative weights are adjusted by two independent regularization parameters. Our initial tests of this imaging system were performed with an imaging phantom that consists of a translucent plastic cylinder filled with tissue-simulating liquid and two thin-wall glass tubes containing indocyanine green. The reconstruction is compared to the output of a finite element method-based software package NIRFAST and has produced promising results.

Authors
Zhang, X; Badea, C; Jacob, M; Johnson, GA
MLA Citation
Zhang, X, Badea, C, Jacob, M, and Johnson, GA. "Development of a noncontact 3-D fluorescence tomography system for small animal in vivo imaging." United States. February 16, 2009.
PMID
19587837
Source
pubmed
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
7191
Publish Date
2009
Start Page
nihpa106691
DOI
10.1117/12.808199

Medical imaging

Medical imaging forms a key part of clinical diagnosis, and improvements in the quality and type of information available from such images have extended the diagnostic accuracy and range of new applications in health care. Medical imaging plays an important role in neurology, cardiology, and cancer centers. This chapter provides a brief overview of the basic physics, instrumentation, and clinical applications of each imaging modality and recent technological advances. Planar X-ray imaging is used for diagnosing bone breaks, lung disease, a number of gastrointestinal (GI) diseases (fluoroscopy), and conditions of the genitourinary tract, such as kidney stones. In contrast to X-ray, ultrasound, and MRI, nuclear medicine imaging techniques do not produce an anatomical map of the body, but instead image the spatial distribution of radioactive materials that are introduced into the body. Ultrasound is non-ionizing, real-time, portable, and inexpensive compared with other clinical imaging modalities. Ultrasound is particularly functional for obstetrics and quantification of blood flow using Doppler measurements. The major uses of MRI are in the areas of brain disease, spinal disorders, angiography, cardiac assessment, and musculoskeletal damage. Diffuse Optical Imaging is characterized by its noninvasive nature, chemical specificity, and good temporal resolution. NIR methods are used in mammography and real-time monitoring of blood oxygenation levels of patients during medical procedures. © 2008 Elsevier Inc. All rights reserved.

Authors
Zhang, X; Smith, N; Webb, A
MLA Citation
Zhang, X, Smith, N, and Webb, A. "Medical imaging." Biomedical Information Technology. December 1, 2008. 3-27.
Source
scopus
Publish Date
2008
Start Page
3
End Page
27
DOI
10.1016/B978-012373583-6.50005-0

A spatial and temporal comparison of hemodynamic signals measured using optical and functional magnetic resonance imaging during activation in the human primary visual cortex

Functional near infrared spectro-imaging (fNIRSI) is potentially a very useful technique for obtaining information about the underlying physiology of the blood oxygenation level dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). In this paper the temporal and spatial statistical characteristics of fNIRSI data are compared to those of simultaneously acquired fMRI data in the human visual cortex during a variable-frequency reversing checkerboard activation paradigm. Changes in the size of activated volume caused by changes in checkerboard reversal frequency allowed a comparison of the behavior of the spatial responses measured by the two imaging methods. fNIRSI and fMRI data were each analyzed using standard correlation and fixed-effect group analyses of variance pathways. The statistical significance of fNIRSI data was found to be much lower than that of the fMRI data, due mainly to the low signal-to-noise of the measurements. Reconstructed images also showed that, while the time-course of changes in the oxy-, deoxy-, and total hemoglobin concentrations all exhibit high correlation with that of the BOLD response, the changes in the volume of tissue measured as "activated" by the BOLD response demonstrate a closer similarity to the corresponding changes in the oxy- and total hemoglobin concentrations than to that of the deoxyhemoglobin. © 2006 Elsevier Inc. All rights reserved.

Authors
Toronov, VY; Zhang, X; Webb, AG
MLA Citation
Toronov, VY, Zhang, X, and Webb, AG. "A spatial and temporal comparison of hemodynamic signals measured using optical and functional magnetic resonance imaging during activation in the human primary visual cortex." NeuroImage 34.3 (2007): 1136-1148.
PMID
17134913
Source
scival
Published In
NeuroImage
Volume
34
Issue
3
Publish Date
2007
Start Page
1136
End Page
1148
DOI
10.1016/j.neuroimage.2006.08.048

Level-set algorithm for the reconstruction of functional activation in near-infrared spectroscopic imaging

We introduce a new algorithm for the reconstruction of functional brain activations from near-infrared spectroscopic imaging (NIRSI) data. While NIRSI offers remarkable biochemical specificity, the attainable spatial resolution with this technique is rather limited, mainly due to the highly scattering nature of brain tissue and the low number of measurement channels. Our approach exploits the support-limited (spatially concentrated) nature of the activations to make the reconstruction problem well-posed. The new algorithm considers both the support and the function values of the activations as unknowns and estimates them from the data. The support of the activations is represented using a level-set scheme. We use a two-step alternating iterative scheme to solve for the activations. Since our approach uses the inherent nature of functional activations to make the problem well-posed, it provides reconstructions with better spatial resolution, fewer artifacts, and is more robust to noise than existing techniques. Numerical simulations and experimental data indicate a significant improvement in the quality (resolution and robustness to noise) over standard techniques such as truncated conjugate gradients (TCG) and simultaneous iterative reconstruction technique (SIRT) algorithms. Furthermore, results on experimental data obtained from simultaneous functional magnetic resonance imaging (fMRI) and optical measurements show much closer agreement of the optical reconstruction using the new approach with fMRI images than TCG and SIRT. © 2006 Society of Photo-Optical Instrumentation Engineers.

Authors
Jacob, M; Bresler, Y; Toronov, V; Zhang, X; Webb, A
MLA Citation
Jacob, M, Bresler, Y, Toronov, V, Zhang, X, and Webb, A. "Level-set algorithm for the reconstruction of functional activation in near-infrared spectroscopic imaging." Journal of Biomedical Optics 11.6 (2006).
PMID
17212552
Source
scival
Published In
Journal of Biomedical Optics
Volume
11
Issue
6
Publish Date
2006
DOI
10.1117/1.2400595

Integrated measurement system for simultaneous functional magnetic resonance imaging and diffuse optical tomography in human brain mapping

An integrated measurement system has been developed for performing simultaneous functional magnetic resonance imaging (fMRI) and diffuse optical tomography (DOT) for human brain mapping experiments. The components of this system consist of a MRI-compatible multioverlapping-channel near-infrared (NIR) optical probe, techniques for accurate and reliable coregistration of optical and fMRI results, and an optical image reconstruction algorithm with structural and physiological constraints derived from the MRI data. The optical probe is fully MRI compatible in that it produces negligible MR image distortion and does not require any modification to the MRI scanner or data acquisition protocols. This probe can be attached to virtually any part of the head without imposing limits on optical data acquisition. Coregistration of images from fMRI and optical measurements is achieved by localizing the positions of the optical fibers using MRI markers. Human studies show successful implementation of the entire system. © 2006 American Institute of Physics.

Authors
Zhang, X; Toronov, VY; Webb, AG
MLA Citation
Zhang, X, Toronov, VY, and Webb, AG. "Integrated measurement system for simultaneous functional magnetic resonance imaging and diffuse optical tomography in human brain mapping." Review of Scientific Instruments 77.11 (2006).
PMID
21399741
Source
scival
Published In
Review of Scientific Instruments
Volume
77
Issue
11
Publish Date
2006
DOI
10.1063/1.2364138

Reconstruction of functional activations in diffuse optical imaging

We propose a new algorithm for the estimation of functional activations in diffuse optical imaging. Our approach considers the activations to be support limited. We simultaneously estimate the function values as well as the support from the available measurements. Since this scheme exploit the structure inherent to functional imaging, it provide reconstructions with better spatial resolution and is more robust to noise. © 2006 IEEE.

Authors
Jacob, M; Toronov, V; Bresler, Y; Zhang, X; Webb, A
MLA Citation
Jacob, M, Toronov, V, Bresler, Y, Zhang, X, and Webb, A. "Reconstruction of functional activations in diffuse optical imaging." 2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro - Proceedings 2006 (2006): 594-597.
Source
scival
Published In
2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro - Proceedings
Volume
2006
Publish Date
2006
Start Page
594
End Page
597

Group analysis of FMRI and NIR data simultaneously acquired during visual stimulation in humans

We use our new combined functional near infrared spectro-imaging (fNIRSI) and magnetic resonance imaging (MRI) technique to compare fMRI and fNIRSI data at different activation conditions, to obtain new information about the underlying physiology of the blood oxygen level dependent (BOLD) signal used in fMRI, and to assess statistical characteristics of spatial functional information provided by the group analysis of fNIRSI data. To achieve these goals we have acquired simultaneously fNIRSI and fMRI data during the presentation of the checkerboard reversing with different frequencies, and analyzed these data following the standard correlation and group analysis of variance pathway used in functional neuroimaging. We have found that while the time courses of oxy-, deoxy-, and total- hemoglobin responses are equally well correlated with the time course of the BOLD response, the spatial pattern and magnitude of the BOLD response is better related to those of the oxy-, and total- hemoglobin responses rather than to the deoxyhemoglobin response. The statistical significance of the fNIRSI group maps is inferior to that of fMRI, and can be particularly compromised by the anatomical features of subjects.

Authors
Toronov, VY; Zhang, X; Webb, AG
MLA Citation
Toronov, VY, Zhang, X, and Webb, AG. "Group analysis of FMRI and NIR data simultaneously acquired during visual stimulation in humans." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6163 (2006).
Source
scival
Published In
Proceedings of SPIE
Volume
6163
Publish Date
2006
DOI
10.1117/12.697069

Simultaneous integrated functional magnetic resonance imaging and optical tomography in the near infrared spectrum (SINFONIS) for studying hemodynamic and neuronal responses in the human brain

Blood oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) study has become an important method for neuroimaging. However, the underlying mechanism of the BOLD signal has not yet been understood completely. In contrast, near infrared optical spectroscopy (NIRS) can be used for direct measurements of oxy- and deoxyhemoglobin concentrations. Its response time is on the order of milliseconds, which makes possible studying the “fast” neuronal in addition to the “slow” hemodynamic responses. Previous studies have demonstrated that the integration of the two techniques can decouple the contributions from blood flow and deoxyhemoglobin concentration to the BOLD signal, although with very limited spatial resolution. In this study, a complete methodology of human brain mapping with simultaneous integrated fMRI and optical tomography in the near-infrared spectrum (SINFONIS) has been established. It features an MRI-compatible optical probe that can be placed over any region of the human brain and fits into a standard MRI birdcage head-coil producing minimal MR image distortion. True three-dimensional optical imaging has been achieved by diffuse optical tomography (DOT) using a perturbation approach of the diffusion equation. A Monte Carlo method has been used to simulate light transport in a subject-specific realistic head model and to subsequently determine the sensitivity function of the discretized Born solution to the diffusion equation. As a result, the linearized inverse problem could be solved using a variety of existing algorithms. The further integration of additional MRI or optical measurement techniques into the current method could be achieved without significant modification to existing hardware and protocols of experiment. The hemodynamic responses reconstructed from DOT have shown reasonably good consistency with that of the BOLD fMRI result. It has been discovered from the correspondence between the two results that the change in oxyhemoglobin concentration may also play a secondary role in the BOLD signal. However, this hypothesis needs further systematic studies, such as determining the effect of oxyhemoglobin on the gradient of the extravascular magnetic susceptibility and its subsequent effect on T2*.

Authors
Zhang, X
MLA Citation
Zhang, X. Simultaneous integrated functional magnetic resonance imaging and optical tomography in the near infrared spectrum (SINFONIS) for studying hemodynamic and neuronal responses in the human brain. Ed. A Webb. 2005. (PhD Thesis)
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Publish Date
2005

Simultaneous integrated diffuse optical tomography and functional magnetic resonance imaging of the human brain

A complete methodology has been developed to integrate simultaneous diffuse optical tomography (DOT) and functional magnetic resonance imaging (MRI) measurements. This includes development of an MRI-compatible optical probe and a method for accurate estimation of the positions of the source and detector optodes in the presence of subject-specific geometric deformations of the optical probe. Subject-specific head models are generated by segmentation of structural MR images. DOT image reconstruction involves solution of the forward problem of light transport in the head using Monte Carlo simulations, and inversion of the linearized problem for small perturbations of the absorption coefficient. Initial results show good co-localization between the DOT images of changes in oxy- and deoxyhemoglobin concentration and functional MRI data. © 2005 Optical Society of America.

Authors
Zhang, X; Toronov, VY; Webb, AG
MLA Citation
Zhang, X, Toronov, VY, and Webb, AG. "Simultaneous integrated diffuse optical tomography and functional magnetic resonance imaging of the human brain." Optics Express 13.14 (2005): 5513-5521.
PMID
19498547
Source
scival
Published In
Optics express
Volume
13
Issue
14
Publish Date
2005
Start Page
5513
End Page
5521
DOI
10.1364/OPEX.13.005513

Magnetic resonance microimaging and numerical simulations of velocity fields inside enlarged flow cells used for coupled NMR microseparations

The coupling of various chemical microseparation methods with small-scale NMR detection is a growing area in analytical chemistry. The formation of enlarged flow cells within the active volume of the NMR detector can significantly increase the coil filling factor and hence the signal-to-noise ratio of the NMR spectra. However, flow cells can also lead to deterioration of the separation efficiency due to the development of complex flow patterns, the form of which depend on the particular geometry of the flow cell and the flow rate used. In this study, we investigated the low characteristics in different flow cell geometries relevant to the coupling of capillary liquid chromatography and NMR. Computational fluid dynamics was used to simulate fluid flow inside flow cells with a volume of ∼1 μL. Magnetic resonance microimaging was used to measure experimentally the velocity fields inside these flow cells. The results showed good agreement between experiment and simulation and demonstrated that a relatively gradual expansion and contraction is necessary to avoid areas of weak recirculation and strong radial velocities, both of which can potentially compromise separation efficiency. © 2005 American Chemical Society.

Authors
Zhang, X; Webb, AG
MLA Citation
Zhang, X, and Webb, AG. "Magnetic resonance microimaging and numerical simulations of velocity fields inside enlarged flow cells used for coupled NMR microseparations." Analytical Chemistry 77.5 (2005): 1338-1344.
PMID
15732916
Source
scival
Published In
Analytical Chemistry
Volume
77
Issue
5
Publish Date
2005
Start Page
1338
End Page
1344
DOI
10.1021/ac048532b

Spatial and temporal hemodynamic study of human primary visual cortex using simultaneous functional MRI and diffuse optical tomography

Blood oxygenation level dependent (BOLD) functional MRI and near infrared optical tomography have been widely used to investigate hemodynamic responses to functional stimulation in the human brain. In this paper, we present a complete methodology for integrating the two imaging modalities to study the underlying physiological mechanism of the hemodynamic response in primary visual cortex. Using a specially designed MRI-compatible optical probe, optical imaging was conducted using a frequency-domain near infrared spectrometer. Three-dimensional optical image reconstruction was based on diffuse optical tomography (DOT) using a perturbative approach. The sensitivity function of the forward problem was obtained using Monte Carlo simulations. From preliminary results, the spatial activation pattern of changes in deoxyhemoglobin concentration is consistent with the BOLD signal map. The patterns of oxy- and deoxyhemoglobin changes are also very similar to one another. The temporal hemodynamic response shows an increased total hemoglobin concentration, which indicates an increased cerebral blood volume (CBV) during physiological activation. © 2005 IEEE.

Authors
Zhang, X; Toronov, VY; Webb, AG
MLA Citation
Zhang, X, Toronov, VY, and Webb, AG. "Spatial and temporal hemodynamic study of human primary visual cortex using simultaneous functional MRI and diffuse optical tomography." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 7 VOLS (2005): 727-730.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
7 VOLS
Publish Date
2005
Start Page
727
End Page
730

The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans

The integration of near-infrared (NIR) and functional MRI (fMRI) studies is potentially a powerful method to investigate the physiological mechanism of human cerebral activity. However, current NIR methodologies do not provide adequate accuracy of localization and are not fully integrated with MRI in the sense of mutual enhancement of the two imaging modalities. Results are presented to address these issues by developing an MRI-compatible optical probe and using diffuse optical tomography for optical image reconstruction. We have developed a complete methodology that seamlessly integrates NIR tomography with fMRI data acquisition. In this paper, we apply this methodology to determine both hemodynamic and early neuronal responses in the visual cortex in humans. Early results indicate that the changes in deoxyhemoglobin concentration from optical data are co-localized with fMRI BOLD signal changes, but changes in oxyhemoglobin concentration (not measurable using fMRI) show small spatial differences.

Authors
Zhang, X; Toronov, VY; Fabiani, M; Gratton, G; Webb, AG
MLA Citation
Zhang, X, Toronov, VY, Fabiani, M, Gratton, G, and Webb, AG. "The study of cerebral hemodynamic and neuronal response to visual stimulation using simultaneous NIR optical tomography and BOLD fMRI in humans." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5686 (2005): 566-572.
PMID
21776185
Source
scival
Published In
Proceedings of SPIE
Volume
5686
Publish Date
2005
Start Page
566
End Page
572
DOI
10.1117/12.593435

Near-infrared study of the underlying physiology of the functional magnetic resonance signal in humans during hypoxia

We use near-infrared spectroscopy to investigate hemodynamic changes in humans during a breath holding exercise and their influence on the BOLD fMRI signal. We have quantitatively compared the BOLD fMRI signals with the hemoglobin concentration changes using correlation analysis of NIRS and fMRI data.

Authors
Toronov, VY; Zhang, X; Webb, AG
MLA Citation
Toronov, VY, Zhang, X, and Webb, AG. "Near-infrared study of the underlying physiology of the functional magnetic resonance signal in humans during hypoxia." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5686 (2005): 543-546.
PMID
21769244
Source
scival
Published In
Proceedings of SPIE
Volume
5686
Publish Date
2005
Start Page
543
End Page
546
DOI
10.1117/12.593434

Methodology development for simultaneous diffuse optical tomography and magnetic resonance imaging in functional human brain mapping

We present an integrated methodology for human brain mapping by simultaneous BOLD fMRI and NIR imaging. This methodology consists of three innovative components: the construction of MRI-compatible optical probes that can be affixed to any part of the human head inside a standard MRI head-coil with minimal MR image distortion, the accurate determination of optode positions on the head from MR images, and the application of a perturbation approach and Monte Carlo method to compute the integral kernel of the Born solution to the diffusion equation for baseline optical properties. This integrated approach has been used to demonstrate promising capabilities for studying functional hemodynamic activation in human visual cortex by simultaneous fMRI and NIR tomography.

Authors
Zhang, X; Toronov, VY; Webb, AG
MLA Citation
Zhang, X, Toronov, VY, and Webb, AG. "Methodology development for simultaneous diffuse optical tomography and magnetic resonance imaging in functional human brain mapping." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5686 (2005): 453-463.
PMID
21796235
Source
scival
Published In
Proceedings of SPIE
Volume
5686
Publish Date
2005
Start Page
453
End Page
463
DOI
10.1117/12.593432

Signal and image processing techniques for functional near-infrared imaging of the human brain

Near-infrared spectro-imaging (NIRSI) is a quickly developing method for the in-vivo imaging of biological tissues. In particular, it is now extensively employed for imaging the human brain. In this non-invasive technique, the information about the brain is obtained from the analysis of spatial light bundles formed by the photons traveling from light sources to detectors placed on the surface of the head. Most significant problems in the functional brain NIRSI are the separation of the brain information from the physiological noise in non-cerebral tissues, and the localization of functional signals. In this paper we describe signal and image processing techniques we developed in order to measure two types of functional cerebral signals: the hemodynamic responses, and neuronal responses.

Authors
Toronov, VY; Zhang, X; Fabiani, M; Gratton, G; Webb, AG
MLA Citation
Toronov, VY, Zhang, X, Fabiani, M, Gratton, G, and Webb, AG. "Signal and image processing techniques for functional near-infrared imaging of the human brain." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5696 (2005): 117-124.
PMID
21738383
Source
scival
Published In
Proceedings of SPIE
Volume
5696
Publish Date
2005
Start Page
117
End Page
124
DOI
10.1117/12.593345

Feasibility study of a rotational step-and-shoot IMRT treatment planning approach

Purpose: Rotational step-and-shot IMRT (r-IMRT) could improve delivery efficiency with good dose conformity, especially if it can leverage the burst mode of the accelerator where radiation is turned on/off momentarily while the gantry rotates continuously. The challenge for the r-IMRT planning is to minimize the number of beams to achieve a fast and smooth rotational delivery. Methods: Treatment plans for r-IMRT were created using an in-house treatment planning system. To generate the plan using a very few beams, gantry angle was optimized by weighting the beam monitoring unit (MU), and beam shape optimization was a combination of column search with k-means clustering. A prostate case and a head and neck case were planned using r-IMRT. The dosimetry is compared to s-IMRT planned with Varian Eclipse treatment planning system. Results: With the same PTV dose coverage D95=100%, the r-IMRT plans shows comparable sparing as the s-IMRT plans in the prostate for the rectum D10cc and the bladder Dmean, and in the head and neck for the spinal cord Dmax, the brain stem Dmax, the left/right parotid Dmean, the larynx Dmean, and the mandible Dmean. Both plans meet the established institutional clinical dosimetric criteria. The r-IMRT plan uses 19 beam/405 MU for the prostate, and 68 beam/880 MU for the head and neck, while the s-IMRT uses 7 beam/724 MU and 9 beam/1812 MU, respectively. Compared to the corresponding s-IMRT, r-IMRT has a reduction of MUs of 44% for the prostate case and 41% for the head and neck case. Conclusions: We have demonstrated the feasibility of a rotational step & shoot IMRT treatment planning approach that significantly shortens the conventional IMRT treatment beam-on time without degrading the dose comformity. © 2014 American Association of Physicists in Medicine

Authors
Zhu, X; Chang, S; Cullip, T; Yuan, L; Lian, J; Zhang, X; Tang, X; Tracton, G; Dooley, J
MLA Citation
Zhu, X, Chang, S, Cullip, T, Yuan, L, Lian, J, Zhang, X, Tang, X, Tracton, G, and Dooley, J. "Feasibility study of a rotational step-and-shoot IMRT treatment planning approach." The American Association of Physicists in Medicine (AAPM) Annual Meeting. 2014.
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Monitoring brain dimpling and intracortical micro-electrode arrays with high resolution MRI in rats

Synopsis High-resolution MRI has been used to monitor the placement and effects of implanted arrays of micro-electrodes in the brains of rats. Dimpling of the brain is strongly implicated in the long-term quality of neural recordings, and imaging of large electrode arrays shows this in vivo. In addition, both implanted self-resonant coils for short-term studies, and external surface coils for long-term studies have been shown to be able to monitor electrode location and orientation in vivo. Introduction Long-term failure of chronic neural implants to record unit activity can be attributed to many factors including initial insertion trauma (i.e., micro-hemorrhaging and dimpling of the brain), neuronal cell loss, and scarring due to active gliosis around the implant. Actual data required to elucidate the relative contributions of these factors in loss of neural recordings is scarce due in part to the lack of effective real-time implant monitoring techniques. Currently, the overall implant system represents a “black-box”, in which the state of the neural interface can only be hypothesized from electrophysiological recordings and electrode impedance. Questions concerning the time course of brain compression (dimpling) as observed during electrode implants, orientation of the pliable electrodes inside the brain, and formation of encapsulation sheath and their effect on recording performance are not clearly understood. Here we present preliminary data showing the feasibility of using high resolution in vivo MRI to detect brain dimpling and also to image the location, geometry and integrity of implanted microelectrode arrays. Materials and Methods Male Sprague Dawley rats (400-500g) were implanted with 50μm tungsten microwire arrays (16 closely spaced or 4 sparsely space): implants were either in primary sensory or motor cortical areas.Post-surgical MRI was performed on a horizontal bore 7 tesla magnet, with a 12 cm diameter gradient set and a Varian Direct Drive console. Two different RF coil setups have been used. In the first, a rectangular surface coil (2.5 x 2 cm) is placed around the micro-electrode array and is used in transmit-receive mode. The second arrangement uses a self-resonant coil which is implanted on to the skull surrounding the craniotomy during surgery (Fig 1A), forms part of the acrylic head cap used for stabilization of the electrode array, and is then coupled to the transmit/receive coil by mutual inductance. Reduction of magnetic susceptibility-induced artifacts in the frequency dimension was achieved using the method of Chang and Fitzpatrick [1 ] with reversal of the polarity of the frequency encoding gradient for successive transients. Results Figure B shows one image acquired using the implanted coil, the high signal-to-noise of the small coil results in a very short data acquisition time. Figure 1C shows two-dimensional slices and a three-dimensional reconstruction of an implanted four-microelectrode array, in which the position, relative orientation and depth of insertion of the microelectrodes can easily be seen. No dimpling of the brain is seen, and there is also no evidence of trauma or swelling in the brain. Figure 1D shows that dimpling of the brain can also be detected soon after insertion of a large, 16-element microelectrode array. Conclusion The results show that it is possible to visualize the locations of implanted micro-electrodes in vivo as well as to see subtle effects such as brain dimpling. For short-term studies, implanted RF coils give very high signal-to-noise: for chronic studies external surface coils must be used, but still give high quality images. Currently, we are studying the correlation between changes in the relaxation properties of tissue between and surrounding the electrodes and the quality of electrical measurements. References. 1. Chang H, Fitzpatrick J.M. IEEE Trans.Med.Imag. 1992, 11, 319.

Authors
Neuberger, T; Paralikar, K; Zhang, X; Clement, R; Webb, A
MLA Citation
Neuberger, T, Paralikar, K, Zhang, X, Clement, R, and Webb, A. "Monitoring brain dimpling and intracortical micro-electrode arrays with high resolution MRI in rats." International Society of Magnetic Resonance in Medicine (ISMRM) Annual Meeting. May 19, 2007 - May 25, 2007. Berlin, Germany.
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Simultaneous fMRI and event-related near infrared tomography for studying hemodynamic and neuronal responses in human visual cortex

INTRODUCTION In spite of its central role in neuroimaging, BOLD fMRI is an indirect measurement of cerebral hemodynamics, and has a relatively low temporal resolution dictated by the hemodynamic response. In contrast, near infrared optical spectroscopy (NIRS) is a localized direct measurement of oxy- and deoxyhemoglobin concentrations with a response time on the order of milliseconds, which enables it to s tudy the “fast” neuronal responses, such as the event-related optical signals (EROS). NIRS can also be used to study slower hemodynamic changes. Our previous studies have demonstrated that combined fMRI and NIRS can uncouple the contributions due to blood flow deoxyhemoglobin concentrations to the BOLD signals, as well as study the “fast” optical neuronal responses [1], [2]. However, the NIRS method is inferior to fMRI in localizing functional responses. When only a limited number of measurements are available in a highly inhomogeneous structure, such as the human head, optical image reconstruction represents a non-trivial inverse problem. In this work, we performed optical tomography by adapting the method of diffuse optical tomography (DOT) using a perturbation approach of the diffusion equation [3]. To compute the spatially dependent sensitivity point-spread function of the diffusion equation, we used Monte Carlo simulations [4] of light transport in a segmented head model from the high-resolution MR anatomical image. In order to demonstrate the capabilities of our bi-modality imaging technique, we acquired BOLD fMRI and near infrared optical data during functional stimulation on the primary visual cortex of humans. The reconstructed optical image of changes in oxy- and deoxyhemoglobin was compared with the BOLD fMRI study using EPI on a 3-Tesla MR head-scanner. The results show the promising feasibility of measuring hemodynamic and “fast” neuronal responses simultaneously. COMPUTATIONAL Algorithms have been developed to identify MRI markers on the optical probe and consequently reconstruct the positions of the optical sources and detectors. This information is used for Monte Carlo simulations and co-registration of optical and fMRI results. A Monte Carlo simulation software package is used to simulate the integration kernel (the product of photon density and the Green’s function) in the diffusion equation, which in turn can be written as a set of linear equations after discretization. The computation is based on stimulation induced changes in the absorption coefficient in this preliminary investigation. A simultaneous iterative reconstructive technique (SIRT) is used to reconstruct the image of absorption coefficient from the optical signal. The optical image reconstruction is performed with a resolution of (4 mm)3. The solution to the inverse problem is constrained to voxels within the illuminated region of brain, which correspond to values of the integration kernel > 0.01. EXPERIMENTAL The BOLD fMRI studies were performed on a 3-Tesla MR head-scanner (Allegra, Siemens) using a standard EPI pulse sequence (FOV 240 mm, resolution 64x64, slice thickness 4 mm, gap 10%, voxel size 3.75x3.75x4.0 mm3, TR 2000 ms, TE 25 ms, and flip angle 60). A full-head high-resolution T1-weighted 3-D anatomical MR image (MPRAGE) was taken for image co-registration and for the reconstruction of optical source-/detector-positions. It was also used to generate the segmented head model for optical simulations and image reconstruction. A flashing checkerboard was used as visual stimulation with different flashing frequencies (1, 2, 4, 6, and 8 Hz). We designed an d constructed an optical probe specifically for this work which gave negligible MR image distortion. It consists of 16 pairs of optical fibers a s light sources, and 4 detector optical fiber bundles. The near infrared light sources (690 and 830 nm laser-diodes) are amplitude modulated at 150 MHz. Optical data acquisition at a sampling rate of 16 ms was triggered by the MR scanner signal. RESULTS The figures show functional maps for oxyhemoglobin, eoxyhemoglobin and BOLD fMRI signals, from left to right, respectively. Note that the deoxyhemoglobin map is displayed as a negative change for clearer visualization. While the BOLD map is similar to that of deoxyhemoglobin, the oxyhemoglobin map is not the same, indicating that the overall topology of the functional hemodynamic changes can be more complicated than that reproduced in the BOLD maps. The NIRS data had a signal-to-noise ratio sufficiently high to image hemodynamic responses on the single-subject level by averaging data over four stimulation blocks. By averaging optical data over several hundreds of checkerboard reversing stimulations, we have also been able to obtain the time course of the neuronal response, which occurred in the 50 ms time range (data not shown). CONCLUSION Simultaneous fMRI and near infrared optical tomography on adult human heads has been demonstrated. Besides its fast response time, the optical method also provides a spatial resolution close to our BOLD fMRI measurement. It also better localizes the hemodynamic response compared with the traditional NIRS method. Near infrared optical tomography reveals not only the deoxyhemoglobin response as does BOLD fMRI, but also the oxyhemoglobin response and the fast signal due to neuronal activity. Therefore, it provides critical clues of physiological mechanisms of BOLD fMRI signals. Further study is underway into improving image reconstruction algorithms by incorporating scattering and using fMRI and optical data to further develop physiological models of the response to cognitive function. REFERENCES [1] Toronov et al., Neuroimage, 19, 1521 (2003). [2] Wolf et al., Psychophysiology, 40, 521 (2003). [3] Arridge et al., Physics in Medicine and Biology, 42, 841 (1997). [4] Boas et al., Optical Express, 10, 159 (2001).

Authors
Zhang, X
MLA Citation
Zhang, X. "Simultaneous fMRI and event-related near infrared tomography for studying hemodynamic and neuronal responses in human visual cortex." International Society of Magnetic Resoance in Medicine (ISMRM) Annual Meeting. May 7, 2005 - May 13, 2005. Miami Beach, FL.
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Research Areas:

  • Algorithms
  • Animals
  • Computer Simulation
  • Image Interpretation, Computer-Assisted
  • Image Processing, Computer-Assisted
  • Imaging, Three-Dimensional
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence
  • Models, Biological
  • Phantoms, Imaging
  • Sensitivity and Specificity
  • Spectrometry, Fluorescence
  • Tomography
  • Tomography, Optical
  • X-Ray Microtomography