DESCRIPTION (provided by applicant): ISS Inc., in collaboration with Dr. Franceschini of the Massachusetts General Hospital and Dr. Yodh of the University of Pennsylvania, proposes to develop and construct the prototype of a novel instrument to monitor cerebral oxygen metabolism (CMRO2) that combines a frequency-domain near-infrared tissue oximeter (FDNIRS) and a diffusion correlation spectroscopy (DCS) device. Combining FDNIRS and DCS will enable us to measure cerebral hemoglobin oxygenation (SO2) and an index (BFi) of cerebral blood flow (CBF) to estimate CMRO2. Our clinical collaborators Dr. Ellen Grant of Children's Hospitals in Boston, and Dr. Daniel Licht of Children's Hospital of Philadelphia will advise us on optimizing the device for the neonatal ICU clinical setting. The ability to rapidly an accurately assess cerebral metabolism at bedside in neonates is critical to improving patient management in neonatology. Currently there is no bedside tool that can accurately screen for brain injury, monitor injury evolution or assess response to therapy. Head ultrasounds are notoriously insensitive and nonspecific, EEG serves a complementary role, and MRI is too expensive and time-consuming to be used for screening or monitoring, and involves unnecessary risks of destabilizing critically ill infants who must be transported to the MRI suite. Conventional NIRS oximetry has failed to become a routine clinical tool in neonatology due to the poor sensitivity of SO2 in detecting brain injury hours after the insult, when equilibrium between oxygen delivery and consumption is reestablished. The direct measure of cerebral oxygen utilization we propose to measure with this novel instrument will provide higher sensitivity to detect brain injury and the ability to monitor normal and abnormal brain development. If successful, this device will allow for real-time interventions and thus could improve clinical outcome. Our long-term plans encompass the commercialization of the first FDNIRS/DCS cerebral metabolism monitoring system. In phase I we will build the first commercial prototype, start to develop unified acquisition and data analysis software, and test this new system in phantoms and adult human subjects. We will then perform a pilot study in newborns and compare infants with seizure activity confirmed by EEG with healthy controls, to validate the hypothesis that a measure of oxygen consumption is better able to diagnose brain damage than measure of hemoglobin oxygenation. While CMRO2 monitoring has been performed previously in a research setting, by combining ISS FDNIRS systems with lab-built DCS instrumentation, these measurements have required highly trained operators and data analysis by optical imaging experts. Our goal is to transform these cumbersome research systems into a more robust turnkey device that will enable medical staff to obtain clinically and relevant measurements at the bedside. After completion of the Phase I portion of the project, we will proceed with Phase II, during which we plan to refine the system and start demonstrating the clinical relevance of our CMRO2 measurements in three hospitals (Brigham and Women's and Children's Hospitals in Boston, and Children's Hospital of Philadelphia with Dr. Daniel Licht). If the plan is accepted in its entirety, we expect to complete development of the FDNIRS/DCS system, which we call MetaOx, within the projected four-year period. PUBLIC HEALTH RELEVANCE: Newborn brain injury causes significant morbidity. The lack of a bedside monitor for newborn brain health is hindering progress in care that could improve neurodevelopmental outcomes. The overall goal of this SBIR is to develop an instrument with which to quantify cerebral oxygen metabolism in at the bedside to be used in neonatal intensive care units. Such a device will have significant clinical utility for assessing cerebral tissue injuy and disease, and to follow response to treatment.

Newborn brain injury causes significant morbidity. The lack of a bedside monitor for newborn brain health is hindering progress in care that could improve neurodevelopmental outcomes. The overall goal of this SBIR is to develop an instrument with which to quantify cerebral oxygen metabolism in at the bedside to be used in neonatal intensive care units. Such a device will have significant clinical utility for assessing cerebral tissue injuy and disease, and to follow response to treatment.