TR&D4: Emerging Diffuse Optical Technologies for Precision Medicine Project PI: Arjun Yodh, PhD Abstract This proposal aims to develop and utilize diffuse optical technologies for precision medicine. Diffuse optics is a field of biomedical optics that uses near-infrared (NIR) light to non-invasively probe living tissues located millimeters to centimeters below tissue surfaces (deep tissues). NIR light is strongly scattered in tissue but is weakly absorbed; thus, it can penetrate long distances in tissue. Under these conditions, light transport is well approximated as a diffusive process. Using this diffusion model, it is possible to quantitatively separate tissue scattering from tissue absorption and thus to carry out optical spectroscopy of deep tissues. Analysis of these optical spectra, in turn, permits determination of the concentration of tissue chromophores. Use of the diffusion equation also enables tomographic image reconstruction of tissue optical and physiological properties. The proposed work uses two types of Diffuse Optical Spectroscopy (DOS), frequency-domain (FD-DOS) and broadband (bDOS) diffuse optical spectroscopy, to measure tissue absorption and scattering, which in turn permits quantitative determination of the tissue concentrations of important physiological parameters such as oxy- and deoxy-hemoglobin, lipid and water, and both oxidized and reduced forms of cytochrome-c-oxidase. The proposed work also utilizes a qualitatively different optical technique called Diffuse Correlation Spectroscopy (DCS), which probes temporal fluctuations of light scattered in tissue that are sensitive to blood flow. The combination of oxygen saturation and blood flow information from FD-DOS/DCS can be used to derive quantitative information about tissue oxygen metabolism (CMRO2) based on hemodynamics. The combination of bDOS/FD-DOS and bDOS-alone can be used to derive metrics of mitochondrial (cellular) metabolism. These complementary metrics of tissue metabolism provide a new window into tissue health. The proposed projects will provide unique benefits in clinical research applications. The technology is portable, compatible with a wide range of measurement environments, and offers unique diagnostic capabilities for dynamic physiological monitoring. These capabilities, and the comparatively low cost of optical devices, complement the MRI methods under development in the center. Each aim of TRD4 addresses technological needs with potential to facilitate individualized treatment for patients, i.e., precision medicine. Aim 1 focuses on real-time bedside measurements of cerebral blood flow in regions of the brain covered by hair; it has immediate applications in intensive care studies of brain-injured patients and for real time monitoring of neuromodulation therapies. Aim 2 develops broadband spectroscopic instrumentation and combines it with FD-DOS to measure cytochrome-c-oxidase (CCO) concentration in both its oxidized and reduced forms; CCO is a...