Continuous Photoacoustic Monitoring of Neonatal Stroke in Intensive Care Unit

PROJECT SUMMARY/ABSTRACT Neonatal encephalopathy can arise from fetal hypoxia-ischemia during labor, chronic uteroplacental inflammation, and large cerebral artery embolization primarily arising from dislodgement of a placental thrombus. Because of overlapping clinical presentation, differential diagnosis is often delayed until seizures develop and MRI can be safely performed, a time at which most neuroprotectants are ineffective. Whereas hypothermia is approved for use within 6 hours of birth for hypoxia-ischemia, no treatments have been approved for perinatal arterial ischemic stroke because of the difficulty of definitive diagnosis required for clinical trial stratification at birth. With an estimated incidence of 17-93 per 100,000 live births, the incidence of stroke in the perinatal period rivals the incidence of stroke in adults (17-23 per 100,000). Therefore, a device that could rapidly and reliably identify an area of focal cerebral ischemia soon after birth would have a major impact by enabling the testing of neuroprotectants at an early therapeutic time window that would maximize efficacy. The Brimrose Technology Corporation, partnering with Johns Hopkins University, propose a photoacoustic helmet (PAH) device that can be safely deployed at the bedside in the neonatal intensive care unit to 1) continuously monitor and rapidly identify at-risk neonates, shortly after birth, rapidly allowing them to be triaged to therapy; 2) monitor the progress of therapy; and 3) provide prognostic information to the parents of newborns at risk for life-long brain injury. The PA imaging mechanism is a purely hybrid mechanism, providing rich optical absorbance contrast of tissue oxy- and deoxyhemoglobin through intact scalp and skull. A proof-of-concept of detecting decreased tissue oxyhemoglobin in a 1 cm-induced experimental stroke has been demonstrated with standard laboratory PA laser light source and clinical ultrasound detector. Our goal is to incorporate safer light-emitting diodes (LEDs) and more sensitive ultrasound detectors configured in a neonatal helmet to localize cortical regions of low oxygenation in the newborn. In the proposed Phase-I STTR, we will develop fundamental hardware and software components for effective integration. Aim 1 - Software for safe PAH imaging at high contrast resolution, including deep neural network and optimal spectral unmixing techniques to enable a safe and high-speed LED-based PAH system. Aim 2 - Hardware for modular PAH system, including a fiber-coupled Brimrose ultra-sensitive multi- bounce laser microphone and optimal modular unit design for a PAH imaging at high spatial-temporal-spectral resolution through intact scalp and skull. Aim 3 - Framework for modular PAH system integration, enabling a robust integration of modular units in a PAH system with rigid-body tag registration using optical tracking, in which different neonatal head shapes and need for different imaging specifications can be accommodated. The Phase-I milestone is detection of the full blood O2 saturation range at andlt;10 mm full-width-half-maximum in the transverse plane and 5 mm sensing depth through ex vivo neonatal piglet skull + scalp sample with an integrated set of hardware and software packages, allowing preclinical validation studies to proceed in Phase II.PROJECT NARRATIVE The Brimrose Technology Corporation, partnering with Johns Hopkins University, propose a new brain monitoring device for continuous monitoring of vulnerable neonates in intensive care unit to enable differential diagnosis of early ischemic stroke and minimize the developmental disability. In this STTR phase I project, our goal is to develop fundamental hardware and software packages for modular photoacoustic helmet technology, providing high transcranial sensitivity and spatial resolution of brain regions of low oxygenation by integrating Brimrose multi-bounce laser microphone, safe pulsed light-emitting diode, and modular integration technologies. Such continuous and safe monitoring of vulnerable neonatal brain will provide valuable information for effective treatment planning, therapeutic monitoring, and prognosis to minimize life-long neurologic injury.