TRD2: Interferometric Near Infrared Spectroscopy (iNIRS)

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PROJECT SUMMARY – Technology Research and Development Project #2 The field of diffuse optical spectroscopy (DOS) has long held the promise of non-invasive, deep tissue monitoring with benign, near-infrared light. Yet clinical DOS instrumentation has been challenged by limited quantitative accuracy, lack of depth specificity, and the inherent ambiguity of hemoglobin oxygenation measures. These challenges have been only partially, and inadequately, addressed by existing technologies. Our team at UC Davis recently invented interferometric diffuse optical spectroscopy (iDOS), which overcomes many of these critical roadblocks. In this TRD, we will advance and disseminate two complementary iDOS technologies: 1) Interferometric Diffusing Wave Spectroscopy (iDWS) uses low-cost complementary metal–oxide– semiconductor (CMOS) sensors to create a new class of near-infrared optical devices that measure deep blood flow (BF) index continuously and non-invasively. Employing the optical “trick” of interferometry, iDWS transforms each CMOS pixel into a sensitive detector for coherent light fluctuations that encode deep BF dynamics. Since CMOS camera pixels are cheap and numerous, iDWS improves the performance and reduces the cost of optical BF measurements. Here, we will develop and validate a transformative, multi-exposure iDWS approach, to enable brain and other deep tissue measurements in adult humans with mass-produced, 2D megapixel sensors. While the interferometric approach is established, the multi-exposure approach is new and high impact, enabling a further two order-of- magnitude improvement in performance-to-cost over iDWS. These advances will democratize access to cerebral BF (CBF), leading to 1) better brain-computer interfaces 2) point-of-care assessments of CBF, and 3) wearable CBF monitors, analogous to blood pressure and heart rate monitors. 2) Interferometric Near-Infrared Spectroscopy (iNIRS) enhances quantitative capabilities of iDOS through laser tuning. Critically, iNIRS measures the time-of-flight (TOF) of light with tens of picosecond resolution, enabling direct quantification of optical properties. Additionally, by measuring coherent light fluctuations, iNIRS quantifies blood flow index, with the additional ability to resolve dynamics in depth (e.g. scalp-skull- brain). In this proposal, besides using iNIRS as a quantitative adjunct to conventional continuous wave methods, we will further improve the TOF resolution of iNIRS by an order of magnitude, while achieving spectroscopic (multi-wavelength) capabilities. We will also provide detection of sub-diffuse light at null source-collector separation, enabling integration of iNIRS and fiber-based mesoscopic approaches such as iFLIM (TRD 1) and Optical Coherence Tomography (OCT). Collaborative and service projects are selected to represent settings ranging from microsurgery to non-invasive monitoring, and applications from clinical neuro-monitoring to surgical skill assessment to population screening. These diverse collaborations will help to evaluate and demonstrate the unique capabilities of the iDOS approach.