Development of highly parallelized interferometric near-infrared spectroscopy for the real-time non-invasive measurement of cerebral blood flow

SUMMARY/ABSTRACT Currently, stroke diagnosis requires advanced imaging (e.g., CT, MRI) to distinguish stroke from mimics, which affect up to 58% of individuals presenting with clinical stroke symptoms. Lack of prompt diagnosis for ischemic stroke, as well as exclusion criteria that stem from potentially severe risk factors associated with global tissue plasminogen activator (tPA) administration, resulted in less than 4% of U.S. patients receiving thrombolytic therapy. CT is typically used to rule out presence of a large hemorrhage or bleeding (10-15% of cases) yet frequently cannot be performed in time for effective thrombolysis. Furthermore, while cerebral blood flow (CBF) perfusion is a direct target parameter for management during acute initial intervention and throughout recovery (12-72 hours post treatment), current hardware is either ‘snapshot’ (perfusion CT and ASL-MRI), or highly invasive (EVD probes). As a result, neuro-intensivists are often left assessing brain perfusion indirectly using systemic targets such as cerebral perfusion pressure. There is no currently available clinically effective method to directly measure CBF rapidly, continuously, quantitatively, and non-invasively. Optical methods hold promise for continuous assessment of CBF. However, absolute quantification of CBF has remained a challenge, requiring high brain specificity in addition to time-of-flight information, which enables accounting for head anatomy and optical properties. While interferometric Near-Infrared Spectroscopy (iNIRS), developed by our team, has addressed the challenge of quantification by providing the time-of-flight dimension, it suffers from low photon collection of a single mode fiber, requiring temporal averaging of 10 seconds or longer. On the other hand, multi-speckle approaches demonstrated recently have unprecedented light collection efficiency but to date do not provide absolute quantification of blood flow. A high throughput version of iNIRS is therefore required to obtain rapid and accurate CBF data non-invasively in the adult human brain. To address this critical need, Neuralenz is developing Neuralenz Flow: an integrated platform permitting rapid, non-invasive, real-time measurement of critical factors used to diagnose and treat stroke patients, including CBF, cerebral blood volume, intracranial pressure, and critical closing pressure. In this Phase 1 proposal we will further develop a multi-channel long-wavelength (1064 nm) iNIRS technique with magnetic resonance compatible front-end probe for achieving more than two orders of magnitude higher signal-to-noise ratio compared to our prior state- of-the-art device. We will then comprehensively validate our measurements against gold-standard MR technologies. The outcome of this Phase I study will result in a minimum viable product validated in healthy human subjects capable of real-time measurement of CBF. This technology will have a significant clinical impact on continuous monitoring of neurocritical care patients and in point-of-care diagnosis and treatment of potentially deadly diseases such as stroke and traumatic brain injury.