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Journal ArticleDOI

Multiwavelength three-dimensional near-infrared tomography of the breast: initial simulation, phantom, and clinical results

01 Jan 2003-Applied Optics (Optical Society of America)-Vol. 42, Iss: 1, pp 135-145
TL;DR: The reconstructed tumor from the breast cancer patient was found to have a higher oxy-deoxy hemoglobin concentration and also a higher oxygen saturation level than the background, indicating a ductal carcinoma that corresponds well to histology findings.
Abstract: Three-dimensional (3D), multiwavelength near-infrared tomography has the potential to provide new physiological information about biological tissue function and pathological transformation. Fast and reliable measurements of multiwavelength data from multiple planes over a region of interest, together with adequate model-based nonlinear image reconstruction, form the major components of successful estimation of internal optical properties of the region. These images can then be used to examine the concentration of chromophores such as hemoglobin, deoxyhemoglobin, water, and lipids that in turn can serve to identify and characterize abnormalities located deep within the domain. We introduce and discuss a 3D modeling method and image reconstruction algorithm that is currently in place. Reconstructed images of optical properties are presented from simulated data, measured phantoms, and clinical data acquired from a breast cancer patient. It is shown that, with a relatively fast 3D inversion algorithm, useful images of optical absorption and scatter can be calculated with good separation and localization in all cases. It is also shown that, by use of the calculated optical absorption over a range of wavelengths, the oxygen saturation distribution of a tissue under investigation can be deduced from oxygenated and deoxygenated hemoglobin maps. With this method the reconstructed tumor from the breast cancer patient was found to have a higher oxy-deoxy hemoglobin concentration and also a higher oxygen saturation level than the background, indicating a ductal carcinoma that corresponds well to histology findings.

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Citations
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Journal ArticleDOI
TL;DR: The current state-of-the-art of diffuse optical imaging is reviewed, which is an emerging technique for functional imaging of biological tissue and recent work on in vivo applications including imaging the breast and brain is reviewed.
Abstract: We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.

1,237 citations


Cites background or methods from "Multiwavelength three-dimensional n..."

  • ...This is commonly the case in breast imaging (Dehghani et al 2003b), and in static imaging of the brain (Bluestone et al 2001, Hintz et al 2001, Hebden et al 2002)....

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  • ...FEM has become the method of choice for modelling complex inhomogeneous domains in optical imaging (Bluestone et al 2001, Dehghani et al 2003b), although the finite difference method (FDM) (Culver et al 2003a, Hielscher et al 2004), finite volume method (FVM) (Ren et al 2004) and boundary element…...

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  • ...…to calculate light propagation in non-diffusive domains where the diffusion approximation does not hold (Boas et al 2002, Okada and Delpy 2003, Hayashi et al 2003), or to validate results obtained using other, faster, methods (Schweiger et al 1995, Chernomordik et al 2002b, Dehghani et al 2003a)....

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  • ...3D images are reconstructed from three 2D data sets, each consisting of amplitude and phase measurements (Dehghani et al 2003b)....

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Journal ArticleDOI
TL;DR: The theoretical basis for near-infrared or diffuse optical spectroscopy (NIRS or DOS) is developed, and the basic elements of diffuse optical tomography (DOT) are outlined.
Abstract: This review describes the diffusion model for light transport in tissues and the medical applications of diffuse light. Diffuse optics is particularly useful for measurement of tissue hemodynamics, wherein quantitative assessment of oxy- and deoxy-hemoglobin concentrations and blood flow are desired. The theoretical basis for near-infrared or diffuse optical spectroscopy is developed, and the basic elements of diffuse optical tomography are outlined. We also discuss diffuse correlation spectroscopy, a technique whereby temporal correlation functions of diffusing light are transported through tissue and are used to measure blood flow. Essential instrumentation is described, and representative brain and breast functional imaging and monitoring results illustrate the workings of these new tissue diagnostics.

987 citations

Journal ArticleDOI
TL;DR: The results show that 3D modeling can be combined with measured data from multiple wavelengths to reconstruct chromophore concentrations within the tissue, and it is possible to recover scattering spectra, resulting from the dominant Mie-type scatter present in tissue.
Abstract: Diffuse optical tomography, also known as near infrared tomography, has been under investigation, for non-invasive functional imaging of tissue, specifically for the detection and characterization of breast cancer or other soft tissue lesions. Much work has been carried out for accurate modeling and image reconstruction from clinical data. NIRFAST, a modeling and image reconstruction package has been developed, which is capable of single wavelength and multi-wavelength optical or functional imaging from measured data. The theory behind the modeling techniques as well as the image reconstruction algorithms is presented here, and 2D and 3D examples are presented to demonstrate its capabilities. The results show that 3D modeling can be combined with measured data from multiple wavelengths to reconstruct chromophore concentrations within the tissue. Additionally it is possible to recover scattering spectra, resulting from the dominant Mie-type scatter present in tissue. Overall, this paper gives a comprehensive over view of the modeling techniques used in diffuse optical tomographic imaging, in the context of NIRFAST software package.

684 citations


Cites background or methods from "Multiwavelength three-dimensional n..."

  • ...The initial bulk homogeneous guess of optical properties was calculated using the calibration methods outlined elsewhere [2, 57], which were found to be a=0....

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  • ...It has been found that if the initial estimate, 0, is not too far from the actual parameter distribution, this term can be ignored [2, 44]....

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Journal ArticleDOI
TL;DR: Targeted imaging and therapeutic agents will be developed in tandem through close collaboration between academia and biotechnology, information technology and pharmaceutical industries to improve outcome and reduce collateral effects.

654 citations


Cites background from "Multiwavelength three-dimensional n..."

  • ...Although NIR optical imaging of the breast has a limited resolution due to light scattering effects it can give spectral information (Dehghani et al., 2003) that permits functional measurements associated with haemoglobin concentration and oxygenation, water concentration, lipid content, and…...

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Journal ArticleDOI
TL;DR: This work represents the first reported 3D fluorescence tomography of human breast cancer in vivo based on fluorescence diffuse optical tomography (FDOT), and the measurements demonstrate that FDOT of breast cancer is feasible and promising.
Abstract: We present three-dimensional (3D) in vivo images of human breast cancer based on fluorescence diffuse optical tomography (FDOT). To our knowledge, this work represents the first reported 3D fluorescence tomography of human breast cancer in vivo. In our protocol, the fluorophore Indocyanine Green (ICG) is injected intravenously. Fluorescence excitation and detection are accomplished in the soft-compression, parallel-plane, transmission geometry using laser sources at 786 nm and spectrally filtered CCD detection. Phantom and in vivo studies confirm the signals are due to ICG fluorescence, rather than tissue autofluorescence and excitation light leakage. Fluorescence images of breast tumors were in good agreement with those of MRI, and with DOT based on endogenous contrast. Tumor-to-normal tissue contrast based on ICG fluorescence was two-to-four-fold higher than contrast based on hemoglobin and scattering parameters. In total the measurements demonstrate that FDOT of breast cancer is feasible and promising.

408 citations

References
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Journal ArticleDOI
TL;DR: A review of methods for the forward and inverse problems in optical tomography can be found in this paper, where the authors focus on the highly scattering case found in applications in medical imaging, and to the problem of absorption and scattering reconstruction.
Abstract: We present a review of methods for the forward and inverse problems in optical tomography. We limit ourselves to the highly scattering case found in applications in medical imaging, and to the problem of absorption and scattering reconstruction. We discuss the derivation of the diffusion approximation and other simplifications of the full transport problem. We develop sensitivity relations in both the continuous and discrete case with special concentration on the use of the finite element method. A classification of algorithms is presented, and some suggestions for open problems to be addressed in future research are made.

2,609 citations

Journal ArticleDOI
TL;DR: The cytochrome aa3 spectrum in vivo from the brains of rats after replacing the blood with a fluorocarbon substitute is obtained and an algorithm for calculating the changes in oxygenated and deoxygenated haemoglobin and oxygenated cy tochrome a a3 in tissue from changes in near IR absorption is constructed.

949 citations

Journal ArticleDOI
TL;DR: It is found that DOT provides for localization and quantification of exogenous tissue chromophore concentrations and the use of ICG, an albumin bound absorbing dye in plasma, demonstrates the potential to differentiate disease based on the quantified enhancement of suspicious lesions.
Abstract: We present quantitative optical images of human breast in vivo. The images were obtained by using near-infrared diffuse optical tomography (DOT) after the administration of indocyanine green (ICG) for contrast enhancement. The optical examination was performed concurrently with a magnetic resonance imaging (MRI) exam on patients scheduled for excisional biopsy or surgery so that accurate image coregistration and histopathological information of the suspicious lesions was available. The ICG-enhanced optical images coregistered accurately with Gadolinium-enhanced magnetic resonance images validating the ability of DOT to image breast tissue. In contrast to simple transillumination, we found that DOT provides for localization and quantification of exogenous tissue chromophore concentrations. Additionally our use of ICG, an albumin bound absorbing dye in plasma, demonstrates the potential to differentiate disease based on the quantified enhancement of suspicious lesions.

895 citations

Journal ArticleDOI
TL;DR: The basic idea of DOT is introduced, the history of optical methods in medicine is reviewed, and a review of the tissue's optical properties, modes of operation for DOT, and the challenges which the development of DOT must overcome are detailed.
Abstract: Diffuse optical tomography (DOT) is an ongoing medical imaging modality in which tissue is illuminated by near-infrared light from an array of sources, the multiply-scattered light which emerges is observed with an array of detectors, and then a model of the propagation physics is used to infer the localized optical properties of the illuminated tissue. The three primary absorbers at these wavelengths, water and both oxygenated and deoxygenated hemoglobin, all have relatively weak absorption. This fortuitous fact provides a spectral window through which we can attempt to localize absorption (primarily by the two forms of hemoglobin) and scattering in the tissue. The most important current applications of DOT are detecting tumors in the breast and imaging the brain. We introduce the basic idea of DOT and review the history of optical methods in medicine as relevant to the development of DOT. We then detail the concept of DOT, including a review of the tissue's optical properties, modes of operation for DOT, and the challenges which the development of DOT must overcome. The basics of modelling the DOT forward problem and some critical issues among the numerous implementations that have been investigated for the DOT inverse problem, with an emphasis on signal processing. We summarize with some specific results as examples of the current state of DOT research.

770 citations

Journal ArticleDOI
TL;DR: A finite element method for deriving photon density inside an object, and photon flux at its boundary, assuming that the photon transport model is the diffusion approximation to the radiative transfer equation, is introduced herein.
Abstract: The use of optical radiation in medical physics is important in several fields for both treatment and diagnosis. In all cases an analytic and computable model of the propagation of radiation in tissue is essential for a meaningful interpretation of the procedures. A finite element method (FEM) for deriving photon density inside an object, and photon flux at its boundary, assuming that the photon transport model is the diffusion approximation to the radiative transfer equation, is introduced herein. Results from the model for a particular case are given: the calculation of the boundary flux as a function of time resulting from a delta-function input to a two-dimensional circle (equivalent to a line source in an infinite cylinder) with homogeneous scattering and absorption properties. This models the temporal point spread function of interest in near infrared spectroscopy and imaging. The convergence of the FEM results are demonstrated, as the resolution of the mesh is increased, to the analytical expression for the Green's function for this system. The diffusion approximation is very commonly adopted as appropriate for cases which are scattering dominated, i.e., where mu(s) much greater than mu(a), and results from other workers have compared it to alternative models. In this article a high degree of agreement with a Monte Carlo method is demonstrated. The principle advantage of the FE method is its speed. It is in all ways as flexible as Monte Carlo methods and in addition can produce photon density everywhere, as well as flux on the boundary. One disadvantage is that there is no means of deriving individual photon histories.

685 citations