New near-infrared (NIR) diffuse optical tomography (DOT) approaches were developed to detect, locate, and image small targets embedded in highly scattering turbid media. The first approach, referred to as time reversal optical tomography (TROT), is based on time reversal (TR) imaging and multiple signal classification (MUSIC). The second approach uses decomposition methods of non-negative matrix factorization (NMF) and principal component analysis (PCA) commonly used in blind source separation (BSS) problems, and compare the outcomes with that of optical imaging using independent component analysis (OPTICA). The goal is to develop a safe, affordable, noninvasive imaging modality for detection and characterization of breast tumors in early growth stages when those are more amenable to treatment. The efficacy of the approaches was tested using simulated data, and experiments involving model media and absorptive, scattering, and fluorescent targets, as well as, "realistic human breast model" composed of ex vivo breast tissues with embedded tumors. The experimental arrangements realized continuous wave (CW) multi-source probing of samples and multi-detector acquisition of diffusely transmitted signal in rectangular slab geometry. A data matrix was generated using the perturbation in the transmitted light intensity distribution due to the presence of absorptive or scattering targets. For fluorescent targets the data matrix was generated using the diffusely transmitted fluorescence signal distribution from the targets. The data matrix was analyzed using different approaches to detect and characterize the targets. The salient features of the approaches include ability to: (a) detect small targets; (b) provide three-dimensional location of the targets with high accuracy (~within a millimeter or 2); and (c) assess optical strength of the targets. The approaches are less computation intensive and consequently are faster than other inverse image reconstruction methods that attempt to reconstruct the optical properties of every voxel of the sample volume. The location of a target was estimated to be the weighted center of the optical property of the target. Consequently, the locations of small targets were better specified than those of the extended targets. It was more difficult to retrieve the size and shape of a target. The fluorescent measurements seemed to provide better accuracy than the transillumination measurements. In the case of ex vivo detection of tumors embedded in human breast tissue, measurements using multiple wavelengths provided more robust results, and helped suppress artifacts (false positives) than that from single wavelength measurements. The ability to detect and locate small targets, speedier reconstruction, combined with fluorophore-specific multi-wavelength probing has the potential to make these approaches suitable for breast cancer detection and diagnosis.

Written by an authority involved in the field since its nascent stages, Diffuse Optical Tomography: Principles and Applications is a long-awaited profile of a revolutionary imaging method. Diffuse Optical Tomography (DOT) provides spatial distributions of intrinsic tissue optical properties or molecular contrast agents through model-based reconstruction algorithms using NIR measurements along or near the boundary of tissue. Despite the practical value of DOT, many engineers from electrical or applied mathematics backgrounds do not have a sufficient understanding of its vast clinical applications and portability value, or its uncommon advantages as a tool for obtaining functional, cellular, and molecular parameters. A collection of the author’s research and experience, this book fuses historical perspective and experiential anecdotes with fundamental principles and vital technical information needed to successfully apply this technology—particularly in medical imaging. This reference finally outlines how to use DOT to create experimental image systems and adapt the results of laboratory studies for use in clinical applications including: Early-stage detection of breast tumors and prostate cancer "Real-time" functional brain imaging Joint imaging to treat progressive diseases such as arthritis Monitoring of tumor response New contrast mechanisms and multimodality methods This book covers almost every aspect of DOT—including reconstruction algorithms based on nonlinear iterative Newton methods, instrumentation and calibration methods in both continuous-wave and frequency domains, and important issues of imaging contrast and spatial resolution. It also addresses phantom experiments and the development of various image-enhancing schemes, and it describes reconstruction methods based on contrast agents and fluorescence DOT. Offering a concise description of the particular problems involved in optical tomography, this reference illustrates DOT’s fundamental foundations and the principle of image reconstruction. It thoroughly explores computational methods, forward mathematical models, and inverse strategies, clearly illustrating solutions to key equations.

"In optical imaging, the high random scattering of light in biological tissue can degrade the contrast of an image which could be a drawback in detection of tumors. Polarization based imaging has shown its capability in overcoming such drawbacks over the recent years. It depends on discrimination of randomly polarized light from weakly polarized light yielding an enhanced image contrast. The purpose of this research study was to investigate, compare and assess the imaging potential of two widely used techniques in the field of polarimetric imaging namely, Linear Polarimeter method (uses linearly polarized light) and Rotating Retarder Polarimeter method (uses circularly polarized light) to interrogate targets embedded in turbid biological media. This novel study may contribute to early detection of diseases and pathologies in biological tissues. The polarization properties of the backscattered light from a turbid medium containing a target submerged in a scattering solution were studied. A preclinical optical phantom was designed and the experiments were done in two phases, each phase corresponding to a different polarimetric technique. Specifically, a polystyrene cylinder was used as the target and the turbid medium was simulated by adding skim milk in volume percentage increments in both the phases. The first phase of experiments involved the Rotating Retarder Polarimeter method and the Polarimetric Measurement Matrix Reduction techniques. The images obtained by this method were processed by iv means of a data reduction algorithm, based on Polarimetric Measurement matrix method to calculate the Degree of Linear Polarization (DOLP) image and total intensity (S0) image. The second phase of experiments involved the Linear Polarimeter method. The resulting co-polarized and cross-polarized images from this method were processed to obtain Degree of Polarization (Rpol) images. Both of these experiments were performed using a backscattered polarimetric imaging system. The images obtained by both the techniques were analyzed by computing signal to background ratio (SBR) values and number of pixels detected as edges for every concentration of skim milk solution added to the surrounding medium of the target. The obtained images were then compared to determine the image quality. Experimental results from both these techniques showed that the DOLP images obtained by the Rotating Retarder Polarimeter method provide better contrast in terms of signal to background ratio (SBR) values and number of pixels detected as edges compared to Degree of Polarization (Rpol) images obtained by the linear Polarimeter method. Overall, the contributions of this study suggest that the interrogation of targets in turbid media using circularly polarized light exhibits superior imaging characteristics with respect to linearly polarized light interrogation."--Abstract.

Optical imaging through biological tissues and other scattering media is challenging, as the scattered light creates an extremely high background noise level that makes it difficult to detect objects that are embedded within the media. This thesis examines a relatively unexplored method of separating scattered light from unscattered light that has application to optical imaging through turbid media. The method creates an optical filter that blocks photons based upon their exit trajectory direction. Such a trajectory filter can be used with a collimated beam that transmissively illuminates a scattering medium to create an imaging system in which a shadowgram is formed from those photons that pass through the filter and have a trajectory close to that of the collimated beam. Experiments have shown that such a system is effective up to measured optical depths of 18 to 21 and scattering ratios of 108 to 109 using both coherent and incoherent sources. A micromachined linear array of 50 m x 10 mm collimating holes was developed earlier as a photon trajectory filter and was used to successfully image through media in which the ratio of scattered to unscattered light is extremely high (>107). These results are much better than simple theory would predict. This thesis provides a theoretical basis for the trajectory filter system to allow its performance to be characterized and compared against other optical imaging methods, such as time-domain imaging. Using Monte Carlo simulations, it is found that the trajectory filter method is more effective than pathlength-based methods for imaging through turbid media with moderate levels of scattering, up to ̃optical depths, and that it can be combined with other imaging methods to further improve contrast. Advantages of the trajectory filter method include coherence and wavelength invariance and the ability to perform either wide beam, full-field or narrow beam, scanned imaging. Experimental results are presented for laser and incoherent beams using two types of trajectory filters: spatiofrequency and linear collimating hole array. It is found that the trajectory filter method offers a viable means of transmissively imaging through moderately scattering media at optical and near infrared wavelengths.

Theory/Algorithm/Modeling; Instrumentation and Technology I; Fluorescence Imaging/Spectroscopy (algorithm/model/tomography); Fluorescence Imaging/Image Reconstruction (Experimental); Instrumentation and Technology II; Fluorescence Imaging Technology I; Fluorescence Imaging Technology II; Fluorescence Imaging Technology III; Network for Translational Research in Optical Imaging: Breast Cancer Diffuse Optical Imaging; Breast II - Instrumentation & New Analysis Method; Breast III - Clinical Study; Pre-Clinical/Animal; Instrumentation and Technology III; Clinical/Human Subject Studies.