Diffuse optical tomography, pubmed sept2005-sept2008

Diffuse optical tomography of pain and tactile stimulation: activation in cortical sensory and emotional systems.

Becerra L, Harris W, Joseph D, Huppert T, Boas DA, Borsook D.

P.A.I.N. Group McLean Hospital, Massachusetts General Hospital, Harvard Medical School, USA. lbecerra@mclean.harvard.edu

Using diffuse optical tomography (DOT), we detected activation in the somatosensory cortex and frontal brain areas following tactile (brush) and noxious heat stimulation. Healthy volunteers received stimulation to the dorsum of the right hand. In the somatosensory cortex area, tactile stimulation produced a robust, contralateral to the stimulus, hemodynamic response with a weaker activation on the ipsilateral side. For the same region, noxious thermal stimuli produced bilateral activation of similar intensity that had a prolonged activation with a double peak similar to results that have been reported with functional MRI. Bilateral activation was observed in the frontal areas, oxyhemoglobin changes were positive for brush stimulation while they were initially negative (contralateral) for heat stimulation. These results suggest that based on the temporal and spatial characteristics of the response in the sensory cortex, it is possible to discern painful from mechanical stimulation using DOT. Such ability might have potential applications in a clinical setting in which pain needs to be assessed objectively (e.g., analgesic efficacy, pain responses during surgery).


Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier.

Patwardhan SV, Culver JP.

Washington University School of Medicine, Department of Radiology, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110, USA.

The quantitative accuracy of fluorescence and bioluminescence imaging of small animals can be improved by knowledge of the in situ optical properties of each animal. Obtaining in situ optical property maps is challenging, however, due to short propagation distances, requirements for high dynamic range, and the need for dense spatial, temporal, and spectral sampling. Using an ultrafast gated image intensifier and a pulsed laser source, we have developed a small animal diffuse optical tomography system with multiple synthetic modulation frequencies up to >1 GHz. We show that amplitude and phase measurements with useful contrast-to-noise ratios can be obtained for modulation frequencies over the range of approximately 250 to 1250 MHz. Experiments with tissue simulating phantoms demonstrate the feasibility of reconstructing the absorption and scattering optical properties in a small animal imaging system.


Time-resolved diffuse optical tomography and its application to in vitro and in vivo imaging.

Zhao H, Gao F, Tanikawa Y, Yamada Y.

Tianjin University, State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin 3000072, China. huijuanzhao@tju.edu.cn

This work reviews our research during the past several years on time-resolved (TR) near-infrared diffuse optical tomography (DOT). Following an introduction of the measuring modes, two proposed schemes of image reconstruction in TR-DOT are described: one utilizes the full TR data, and the other, referred to as the modified generalized pulse spectrum technique (GPST), uses the featured data extracted from the TR measurement. The performances of the two algorithms in quantitativeness and spatial resolution are comparatively investigated with 2-D simulated data. TR-DOT images are then presented for phantom experiments, which are obtained by using a 16-channel time-correlated single photon counting system, and the factors affecting the quantification of the reconstruction are discussed. Finally, in vitro and in vivo imaging examples are illustrated for validating the capibility of TR-DOT to provide not only the anatomical but also the physiological information of the objects.

Publication Types:

PMID: 18163810 [PubMed – indexed for MEDLINE]


Multispectral diffuse optical tomography with absorption and scattering spectral constraints.

Li C, Grobmyer SR, Chen L, Zhang Q, Fajardo LL, Jiang H.

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611-6131, USA.

We present a new method to simultaneously reconstruct the images of oxyhemoglobin, deoxyhemoglobin, and water concentrations, as well as the volume fraction images of the scattering particles using continuous wave multispectral diffuse optical tomography with the absorption and scattering spectral prior constraints. In this method, the nonlinear relationship between the reduced scattering coefficient and the volume fraction and the size of the particles is linearized, allowing direct reconstruction of the volume fraction of scattering particles in tissues. The method is validated by a series of numerical simulations, phantom experiments, and in vivo clinical experiments. The initial clinical results indicate that the volume fraction of scattering particles in a malignant tumor is higher than that in a benign tumor.

Publication Types:

PMID: 18059661 [PubMed – indexed for MEDLINE]


Optimization of optode arrangements for diffuse optical tomography: A singular-value analysis.

Culver JP, Ntziachristos V, Holboke MJ, Yodh AG.

We develope a method to optimize the resolution of diffuse optical tomographic instruments. Singular-value analysis of the tomographic weight matrix associated with specific data types, geometries, and optode arrangements is shown to provide a measure of image resolution. We achieve optimization of device configuration by monitoring the resolution measure described. We introduce this idea and demonstrate its utility by optimizing the spatial sampling interval and field-of-view parameters in the parallel-plane transmission geometry employed for diffuse optical breast imaging. We also compare resolution in transmission and remission geometries.

PMID: 18040425 [PubMed – in process]


Fast analytical approximation for arbitrary geometries in diffuse optical tomography.

Ripoll J, Nieto-Vesperinas M, Weissleder R, Ntziachristos V.

Diffuse optical tomography is a novel imaging technique that resolves and quantifies the optical properties of objects buried in turbid media. Typically, numerical solutions of the diffusion equation are employed to construct the tomographic problem when media of complex geometries are investigated. Numerical methods offer implementation simplicity but also significant computation burden, especially when large three-dimensional reconstructions are involved. We present an alternative method of performing tomography of diffuse media of arbitrary geometries by means of an analytical approach, the Kirchhoff approximation. We show that the method is extremely efficient in computation times and consider its potential as a real-time three-dimensional imaging tool.

PMID: 18007854 [PubMed – in process]


Noncontact optical imaging in mice with full angular coverage and automatic surface extraction.

Meyer H, Garofalakis A, Zacharakis G, Psycharakis S, Mamalaki C, Kioussis D, Economou EN, Ntziachristos V, Ripoll J.

Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Heraklion Crete, Greece. heimeyer@iesl.forth.gr

During the past decade, optical imaging combined with tomographic approaches has proved its potential in offering quantitative three-dimensional spatial maps of chromophore or fluorophore concentration in vivo. Due to its direct application in biology and biomedicine, diffuse optical tomography (DOT) and its fluorescence counterpart, fluorescence molecular tomography (FMT), have benefited from an increase in devoted research and new experimental and theoretical developments, giving rise to a new imaging modality. The most recent advances in FMT and DOT are based on the capability of collecting large data sets by using CCDs as detectors, and on the ability to include multiple projections through recently developed noncontact approaches. For these to be implemented, we have developed an imaging setup that enables three-dimensional imaging of arbitrary shapes in fluorescence or absorption mode that is appropriate for small animal imaging. This is achieved by implementing a noncontact approach both for sources and detectors and coregistering surface geometry measurements using the same CCD camera. A thresholded shadowgrammetry approach is applied to the geometry measurements to retrieve the surface mesh. We present the evaluation of the system and method in recovering three-dimensional surfaces from phantom data and live mice. The approach is used to map the measured in vivo fluorescence data onto the tissue surface by making use of the free-space propagation equations, as well as to reconstruct fluorescence concentrations inside highly scattering tissuelike phantom samples. Finally, the potential use of this setup for in vivo small animal imaging and its impact on biomedical research is discussed.


Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging.

Joseph DK, Huppert TJ, Franceschini MA, Boas DA.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, MA 02129, USA. danny@nmr.mgh.harvard.edu

Although most current diffuse optical brain imaging systems use only nearest- neighbor measurement geometry, the spatial resolution and quantitative accuracy of the imaging can be improved through the collection of overlapping sets of measurements. A continuous-wave diffuse optical imaging system that combines frequency encoding with time-division multiplexing to facilitate overlapping measurements of brain activation is described. Phantom measurements to confirm the expected improvement in spatial resolution and quantitative accuracy are presented. Experimental results showing the application of this instrument for imaging human brain activation are also presented. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging.

Publication Types:

PMID: 17068557 [PubMed – indexed for MEDLINE]


Diffuse photon propagation in multilayered geometries.

Sikora J, Zacharopoulos A, Douiri A, Schweiger M, Horesh L, Arridge SR, Ripoll J.

Institute of the Theory of Electrical Engineering, Measurement and Information Systems, Warsaw University of Technology, Koszykowa 75, 00-661 Warsaw, Poland.

Diffuse optical tomography (DOT) is an emerging functional medical imaging modality which aims to recover the optical properties of biological tissue. The forward problem of the light propagation of DOT can be modelled in the frequency domain as a diffusion equation with Robin boundary conditions. In the case of multilayered geometries with piecewise constant parameters, the forward problem is equivalent to a set of coupled Helmholtz equations. In this paper, we present solutions for the multilayered diffuse light propagation for a three-layer concentric sphere model using a series expansion method and for a general layered geometry using the boundary element method (BEM). Results are presented comparing these solutions to an independent Monte Carlo model, and for an example three layered head model.

Publication Types:

PMID: 16424578 [PubMed – indexed for MEDLINE]


Dynamic physiological modeling for functional diffuse optical tomography.

Diamond SG, Huppert TJ, Kolehmainen V, Franceschini MA, Kaipio JP, Arridge SR, Boas DA.

Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA 02129, USA. sdiamond@nmr.harvard.edu

Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n=10, P<0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis.

PMID: 16242967 [PubMed – indexed for MEDLINE]


Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin.

Culver JP, Siegel AM, Franceschini MA, Mandeville JB, Boas DA.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA. culverj@wustl.edu

With the aim of evaluating the relative performance of hemodynamic contrasts for mapping brain activity, the spatio-temporal response of oxy-, deoxy-, and total-hemoglobin concentrations were imaged with diffuse optical tomography during electrical stimulation of the rat somatosensory cortex. For both 6-s and 30-s stimulus durations, total hemoglobin images provided smaller activation areas than oxy- or deoxy-hemoglobin images. In addition, analysis of regions of interest near the sagittal sinus vein show significantly greater contrast in both oxy- and deoxy-relative to total hemoglobin, suggesting that oximetric contrasts have larger draining vein contributions compared to total hemoglobin contrasts under the given stimulus conditions. These results indicate that total hemoglobin and cerebral blood volume may have advantages as hemodynamic mapping contrasts, particularly for large amplitude, longer duration stimulus paradigms.

Publication Types:

PMID: 16084112 [PubMed – indexed for MEDLINE]


Diffuse optical tomography with a priori anatomical information.

Guven M, Yazici B, Intes X, Chance B.

Electrical, Computer, and Systems Engineering Department, Rensselaer Polytechnic Institute, Troy, NY, USA.

Diffuse optical tomography (DOT) poses a typical ill-posed inverse problem with a limited number of measurements and inherently low spatial resolution. In this paper, we propose a hierarchical Bayesian approach to improve spatial resolution and quantitative accuracy by using a priori information provided by a secondary high resolution anatomical imaging modality, such as magnetic resonance (MR) or x-ray. In such a dual imaging approach, while the correlation between optical and anatomical images may be high, it is not perfect. For example, a tumour may be present in the optical image, but may not be discernable in the anatomical image. The proposed hierarchical Bayesian approach allows incorporation of partial a priori knowledge about the noise and unknown optical image models, thereby capturing the function-anatomy correlation effectively. We present a computationally efficient iterative algorithm to simultaneously estimate the optical image and the unknown a priori model parameters. Extensive numerical simulations demonstrate that the proposed method avoids undesirable bias towards anatomical prior information and leads to significantly improved spatial resolution and quantitative accuracy.

Publication Types:

PMID: 15930606 [PubMed – indexed for MEDLINE]


Optical tomographic imaging of small animals.

Hielscher AH.

Department of Biomedical Engineering, Columbia University, ET351 Mudd Building, 500 West 120th Street, MC8904, New York, NY 10027, USA. ahh20004@columbia.edu

Diffuse optical tomography is emerging as a viable new biomedical imaging modality. Using visible and near-infrared light this technique can probe the absorption and scattering properties of biological tissues. The main applications are currently in brain, breast, limb and joint imaging; however, optical tomographic imaging of small animals is attracting increasing attention. This interest is fuelled by recent advances in the transgenic manipulation of small animals that has led to many models of human disease. In addition, an ever increasing number of optically reactive biochemical markers has become available, which allow diseases to be detected at the molecular level long before macroscopic symptoms appear. The past three years have seen an array of novel technological developments that have led to the first optical tomographic studies of small animals in the areas of cerebral ischemia and cancer.

Publication Types:

PMID: 15722019 [PubMed – indexed for MEDLINE]


Improved quantification of small objects in near-infrared diffuse optical tomography.

Srinivasan S, Pogue BW, Dehghani H, Jiang S, Song X, Paulsen KD.

Dartmouth College, Thayer School of Engineering, Hanover, NH 03755, USA. Subha@dartmouth.edu

Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final third step, which uses the estimated size and position information from step 2 to yield quantitatively accurate average values for the optical parameters. The algorithm is tested on simulated and experimental data and is found to be insensitive to object contrast and position. The percentage error between the true and the average recovered value for the absorption coefficient in test images is reduced from 47 to 27% for a 10-mm inclusion, from 38 to 13% for a 15-mm anomaly, and from 28 to 5.5% for a 20-mm heterogeneity. Simulated data with absorbing and scattering heterogeneities of 15 mm diam located in different positions show recovery with less than 15% error in absorption and 6% error in reduced scattering coefficients. The algorithm is successfully applied to clinical data from a subject with a breast abnormality to yield quantitatively increased absorption coefficients, which enhances the contrast to 3.8 compared to 1.23 previously. Copyright 2004 Society of Photo-Optical Instrumentation Engineers.

Publication Types:

PMID: 15568936 [PubMed – indexed for MEDLINE]


Fiber optic in vivo imaging in the mammalian nervous system.

Mehta AD, Jung JC, Flusberg BA, Schnitzer MJ.

Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.

The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications.

Publication Types:

PMID: 15464896 [PubMed – indexed for MEDLINE]


Three-dimensional optical tomographic brain imaging in small animals, part 1: hypercapnia.

Bluestone AY, Stewart M, Lasker J, Abdoulaev GS, Hielscher AH.

Columbia University, Departments of Biomedical Engineering and Radiology, New York, New York 10027, USA.

In this study, we explore the potential of diffuse optical tomography for brain oximetry. While several groups have already reported on the sensitivity of optical measurements to changes in oxyhemoglobin, deoxyhemoglobin, and blood volume, these studies were often limited to single source-detector geometries or topographic maps, where signals obtained from within the brain are projected onto 2-D surface maps. In this two-part study, we report on our efforts toward developing a volumetric optical imaging system that allows one to spatially resolve 3-D hemodynamic effects in rat brains. In part 1, we describe the instrumentation, optical probe design, and the model-based iterative image reconstruction algorithm employed in this work. Consideration of how a priori anatomical knowledge can be incorporated in the reconstruction process is presented. This system is then used to monitor global hemodynamic changes that occur in the brain under various degrees of hypercapnia. The physiologic cerebral response to hypercapnia is well known and therefore allows an initial performance assessment of the imaging system. As expected, we observe global changes in blood volume and oxygenation, which vary linearly as a function of the concentration of the inspired carbon dioxide. Furthermore, experiments are designed to determine the sensitivity of the reconstructions of only 1 mm to inaccurate probe positioning. We determine that shifts can significantly influence the reconstructions. In part 2 we focus on more local hemodynamic changes that occur during unilateral carotid occlusion performed at lower-than-normal systemic blood pressure. In this case, the occlusion leads to a predominantly monohemispherically localized effect, which is well described in the literature. Having explored the system with a well-characterized physiologic effect, we investigate and discuss the complex compensatory cerebrovascular hemodynamics that occur at normotensive blood pressure. Overall, these studies demonstrate the potential and limitations of our diffuse optical imager for visualizing global and focal hemodynamic phenomenon three dimensionally in the brains of small animals. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

Publication Types:

PMID: 15447026 [PubMed – indexed for MEDLINE]

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