Next generation deep tissue quantitative optical imaging

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PROJECT SUMMARY Nearly 20 years of clinical research has shown that near-infrared optical imaging based upon frequency domain diffuse optical spectroscopy (FD-DOS) can be a powerful tool for the study, diagnosis, and personalized treatment of human disease. When used for neuroimaging (i.e. functional near-infrared spectroscopy, fNIRS), FD-DOS can provide a greater imaging depth compared to standard continuous-wave (CW) fNIRS thus reaching deeper cortical layers and providing better distinction from superficial layers. In breast cancer, FD-DOS is effective for predicting individual response to neoadjuvant chemotherapy and similar strong evidence supporting FD-DOS has been collected in critical care, exercise physiology, breast cancer diagnosis, and other applications. Despite this convincing clinical data, FD-DOS has not yet been translated to standard clinical use for any indication. The reasons are two-fold. First, diffuse optical imaging methods, as a whole, still suffer from low spatial resolution and signal-to-noise ratio. Furthermore, clinical applications that can benefit from the advanced quantitation and deeper sensitivity afforded by FD-DOS are reluctant to adopt the method because it lacks scalability for high density, high resolution imaging and is prohibitively complex, slow, and difficult to use. This project will remove these barriers by creating a reflectance-based FD-DOS imaging platform for quantitative deep tissue spectroscopy and tomography with unprecedented scalability, precision, and speed that enables dramatic improvements in accuracy and spatial resolution. This will be enabled by the development and evaluation of massively-scalable multi-frequency FD hardware and software that samples tissue at ultrahigh spatial densities with high precision. Current methods are insufficient because data acquisition is too slow, the hardware needed (e.g. optical devices/fibers and electronics) is too bulky and heavy, and standard data processing and 3D reconstruction algorithms cannot reasonably handle these large datasets. This project introduces innovations in multi-wavelength optical sources and sensitive detectors, multi- frequency FD modulation and demodulation, high spatial density tissue sampling methods, FD phased-array structured interrogation of tissue, and 2D/3D image reconstruction. Improved performance will be demonstrated through human validation studies of breast imaging and quantitative fNIRS. The results will also significantly advance wearable sensing capabilities and improve quantification in other optical modalities such as photoacoustic imaging. No other medical imaging technology can provide quantitative, deep tissue, and real-time measurements of both endogenous and exogenous molecules and tissue scattering parameters in a compact, scalable platform. Together, these advances will usher in a next generation of quantitative tissue optical spectroscopy that lead to improved diagnostics and individualized care, especially in neurology, breast oncology, and personal health. 1