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.
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