BME PhD Dissertation Defense: Tom Cheng

Title: "Continuous noninvasive monitoring of cerebral perfusion and critical closing pressure using speckle contrast optical spectroscopy"

Advisory Committee: David Boas, PhD – BU BME (Research Co-Advisor) Maria Angela Franceschini, PhD – HMS Radiology, MGH (Research Co-Advisor) Darren Roblyer, PhD – BU BME (Chair) Xiaojun Cheng, PhD – BU BME Stefan Carp, PhD – HMS Radiology, MGH

Abstract: Continuous monitoring of brain perfusion is essential in neurocritical care to guide treatment of evolving pathologies and reduce mortality. However, the lack of continuous, noninvasive alternatives in the clinic necessitates invasive monitoring through the skull, which increases patient risk and restricts availability. Diffuse correlation spectroscopy (DCS) is a well-validated, noninvasive optical method that can continuously measure cerebral blood flow (CBF) at the bedside, but signal-to-noise ratio (SNR) limitations hinder its clinical adoption. Speckle contrast optical spectroscopy (SCOS) has emerged as an alternative to DCS, recently demonstrating more than an order of magnitude improvement in SNR compared to standard DCS implementations. Despite SCOS’s performance potential, the difficulty of obtaining accurate CBF measurements from SCOS relative to DCS has been a barrier to its use. This dissertation aims to streamline the calibration of SCOS for accurate CBF measurements and to explore the clinical utility enabled by its superior SNR. First, a systematic camera calibration procedure was developed to correct for camera-related biases in SCOS blood flow measurements, enabling more affordable cameras to be used for human CBF monitoring. Second, this calibration procedure was validated through concurrent SCOS and DCS measurements of human CBF during various physiological maneuvers, demonstrating excellent agreement and confirming SCOS’s overall performance advantage. Finally, SCOS was extended for the first time to continuous, beat-to-beat estimation of critical closing pressure (CrCP), a known correlate of intracranial pressure (ICP) in acute brain injury. For participants in whom SCOS demonstrated sensitivity to cerebral dynamics, SCOS measurements of CBF and CrCP changes closely tracked those of transcranial Doppler (TCD) ultrasound, the current standard for monitoring CBF velocity and CrCP. This work lowers the barrier to accurate CBF monitoring with SCOS and demonstrates the preliminary clinical utility of calibrated SCOS measurements, facilitating its clinical translation to improve patient outcomes.