High Sensitivity Diffuse Optical Tomography of Human Brain Funciton

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Project Summary: This grant will develop speckle contrast optical tomography (SCOT) for imaging of cerebral blood flow dynamics in humans. Real-time maps of cerebral blood flow (CBF) at the bedside are a long sought-after assay for neuro-critical care. Most critically, regional CBF measures can indicate which brain regions may be becoming ischemic and are at danger for hypoxic-ischemic injury. Current clinical methods for imaging CBF include positron emission tomography (PET) and arterial spin labeling with Magnetic Resonance Imaging (ASL- MRI). Both modalities provide only snapshots of CBF, though, thus they miss dynamic events, which are important in many clinical scenarios including acute stroke, traumatic brain injury, and preterm birth. Non-invasive optical techniques are an attractive approach for imaging brain blood dynamics at the bedside. The most widely used non-invasive optical neuroimaging technique uses near infrared spectroscopy (NIRS) to measure fluctuations in hemoglobin concentrations. Over the last decade high-density diffuse optical tomography (HD-DOT) systems have made significant advances in resolution and brain specificity making it an increasingly viable surrogate for functional MRI. However, fNIRS and HD-DOT do not measure flow directly. Separately, there have been considerable advances in laser speckle methods for measuring CBF. The most established deep tissue speckle method, diffuse correlation spectroscopy (DCS), has been developed for in vivo tomographic imaging in rat models of focal ischemia and for monitoring brain perfusion in humans. However, in humans DCS has been limited to few spatial measurements, which precludes tomographic imaging, and by instrumentation that permits only very low signal-to-noise ratio (SNR) measurements. This proposal will address these limitations and develop speckle contrast optical tomography (SCOT), a new method for transcranial optical imaging of relative CBF in humans. SCOT allows for the use of lower speed detectors that could readily be implemented in parallel in modern scientific CMOS cameras. Aim 1 will develop SCOT instrumentation with high-density imaging arrays. Aim 2 will develop anatomically derived head models for reconstructing SCOT images. Aim 3 will validate SCOT-based measures in patients with carotid artery occlusions based on comparison to PET and ASL-MRI. Aim 4 will evaluate the longitudinal feasibility of using SCOT for imaging acute stroke. These studies will represent the culmination of several advances in functional neuroimaging made possible by the research teams’ unique combination of clinical and technical expertise across the domains of neurology, functional neuroimaging and biomedical optics.