Abstract: Occurring after subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) is a major cause of morbidity and mortality. In aneurysmal SAH, DCI occurs in up to 30-50% of survivors. The consequences of DCI are severe, in part because it is often detected too late by conventional monitoring and imaging protocols, preventing timely intervention. Near-infrared (NIR) optical monitoring of relative cerebral blood flow (CBF) after SAH has been performed by diffuse correlation spectroscopy (DCS). DCS has shown the potential of optical CBF measurements, but remains limited to sampling the forehead with marginal brain specificity. Quantitative CBF measurements are further hampered by superficial tissue contamination. Our group recently advanced a new approach called interferometric diffuse optics (iDO). In separate implementations, this new approach has provided highly parallel detection (~300x more channels than conventional single channel DCS detection) and time-of-flight (TOF) information. Here we propose to further enhance and unify these advantages in a single implementation (detection scheme) that improves the measurement signal-to-noise ratio by 100x and channel number by 1000x relative to single channel DCS, while also providing time-of-flight information. This unique approach will improve the SNR of the autocorrelation, from which optical CBF is derived, by ten million-fold compared to DCS (if all channels are pooled). The same system will also provide time-of-flight information to account for variability in head geometry and superficial blood flow and provide quantitative optical CBF that can be compared across time, locations, and subjects. In this proposal, we will develop a 1064 nm iDO system that uses the new concept of coherence engineering to provide TOF information and reduce S-C separation, thus improving photon counts (Aim 1). We will benchmark this new system against existing technologies in our laboratory and validate its capabilities (Aim 2). Finally, we will deploy an iDO instrument in the neuro-intensive care unit (ICU) for observational monitoring of SAH patients across the head and test whether optical CBF can diagnose DCI (Aim 3). Beyond DCI, the interferometric technology delivered here can be applied in ischemic stroke, traumatic brain injury, and other neurological disorders.

Project Narrative: Delayed cerebral ischemia (DCI) after bleeding around the brain is a major cause of illness and death, in part because it is often detected too late. A number of technologies have been applied to this problem with limited success. Here, we will realize transformative improvements in NIR optical cerebral blood flow monitoring technology, increasing signal-to-noise ratio by 100x and detection channel number by 1000x, enabling more comprehensive detection of DCI as a prelude to earlier treatment, which can reduce disability and lengthen life.