Abstract Monitoring intracranial pressure (ICP) is the global standard of care following severe brain injury. The goal of monitoring and treating rises in ICP is to maintain adequate cerebral blood flow (CBF), thereby preventing secondary brain injury. ICP is measured by a small pressure-sensitive probe inserted through the skull, with risk of intracranial hemorrhage and infection, hence used only in the most critically ill patients. More importantly, ICP probes do not directly measure CBF and critical closing pressure (CrCP), the pressure where blood flow ceases, which is needed to correctly assess cerebral perfusion pressure (CPP). Therefore it is not currently possible to separate benign ICP elevations from flow-limiting pressure spikes. A non-invasive monitor of ICP, CBF and CrCP would enable targeted interventions that directly optimize cerebral perfusion and significantly expand the potential use cases for ICP monitoring. Diffuse correlation spectroscopy (DCS) has emerged as a viable tool to monitor CBF, CrCP and ICP. To measure CBF, DCS quantify the timescale of fluctuations in the intensity of coherent, diffusely propagating near-infrared light, which are driven by the motion of red blood cells. DCS measures ICP based on the morphology of the pulsatile blood flow (pCBFi) and it estimates CrCP by means of a linear regression approach between pulsatile blood pressure and pCBFi. While successful proof of concept studies have been conducted by our group and others, the clinical translation of DCS in adults is currently hampered by the challenge of balancing the requirement for high brain sensitivity, which requires large source- detector separations, and the need for high signal to noise ratio (SNR) at high acquisition rates to capture detailed pulsatile blood flow data. Current DCS devices operate at 785 - 850 nm and are limited to separations of 2.5 cm, offering relatively low brain sensitivity, high risk of superficial physiology contamination, and requiring pulse- gated averages of 50-60 cardiac cycles to extract clean pCBFi signals due to limited SNR. Quantification of CBF is strongly affected by scalp blood flow and important morphological information needed to accurately quantify CrCP and ICP is lost during the averaging. To overcome these limitations, we propose to partner with one of the pioneers of superconducting nanowire single photon detectors (SNSPD) technology, Quantum Opus, to develop a compact, low sonic and thermal emission 8 channel SNSPD unit, designed with costs, manufacturability and scalability in mind, that we will integrate with a state-of-the art 1064 nm laser system, heterodyne detection, and fast FPGA correlator to offer bilateral DCS monitoring at 3.5 cm (>50% increase in brain sensitivity) with more than 200-fold increase in SNR with respect to current 785 - 850 nm DCS technology. We will demonstrate the feasibility and initial clinical utility of the SNSPD-DCS in 50 neuro-ICU patients and validate our CBF, CrCP and ICP estimates against TCD, invasive ICP, Hemedex, and patient outcomes. The successful realization of this state-of-the-art non-invasive cerebral perfusion and pressure monitor will enable guided management of patients resulting in improved neurological outcomes.

Narrative: In severe traumatic brain injury intracranial pressure (ICP) is monitored to treat raises in ICP with the goal of maintaining adequate cerebral blood flow (CBF) and critical closing pressure (CrCP) and prevent secondary brain injury. ICP alone cannot separate benign ICP elevations from flow-limiting pressure spikes. By combining superconducting nanowire single photon detectors (SNSPD) with diffuse correlation spectroscopy (DCS) operating at 1064 nm, we propose to develop a bedside CBF, CrCP and ICP monitor that offers a leap forward in performances when compared to existing DCS technology and demonstrate feasibility and utility in the ICU environment. If successful, this device will enable better guided management of a larger number of brain injury patients resulting in improved neurological outcomes.