PROJECT SUMMARY Summary The Brimrose Technology Corporation and Johns Hopkins University are forming a powerful new team to make a new instrument that has the potential to dramatically reduce a major global health problem–perinatal hypoxic- ischemic encephalopathy (HIE)–by enabling early detection during labor. HIE caused by asphyxia is a leading cause of infant fatalities as well as a source of cerebral palsy and other long-term severe neurologic impairments. The medical community has been limited in early diagnosis of HIE because current fetal heart rate monitoring has poor specificity. If identified early, HIE can be treated effectively with therapeutic hypothermia. We are proposing a fetal photoacoustic monitoring system that measures oxyhemoglobin saturation of the sagittal sinus vein draining the fetal cerebral cortex during labor. Sagittal sinus oxyhemoglobin saturation decreases to very low levels when placental gas exchange is impaired (hypoxia) and/or when fetal cerebral perfusion pressure falls (ischemia). The photoacoustic instrument transmits light through the open fontanelle or bone and into cerebral veins and tissue where ultrasound waves are generated. Using near- infrared incident light at discrete wavelengths that are absorbed preferentially by oxy- and deoxy-hemoglobin, ultrasound detected on the fetal scalp at each wavelength can estimate oxyhemoglobin saturation. Brimrose has constructed a novel ultrasound detection technology with sensitivity orders of magnitude greater than the current best-use piezo-electric sensors. This will permit the use of low-power LED light sources rather than cumbersome laser lights now employed, thereby avoiding safety goggle use and promoting greater deployment. The Hopkins team has already validated the ability of a standard photoacoustic system to accurately estimate sagittal sinus oxyhemoglobin saturation through the skull of newborn piglets. The purpose of Phase I is to demonstrate the feasibility of using safe, low power LED light sources with the new ultrasensitive ultrasound sensor to detect critically low sagittal sinus oxyhemoglobin saturation when oxygenation is manipulated. The platform will be based on in-silico simulation to optimize the acoustic and optical pathways for the skull and brain. Real-time measurements on a time scale of seconds will inform the obstetric caregiver of dynamic fluctuations of brain oxygenation during contractions. The Phase II goal is to make a miniaturized photoacoustic device prototype that can report on fetal brain oxygenation. We believe the resulting instrument will provide early detection brain HI with greater specificity and sensitivity, enabling early intervention and treatment and is potentially transferrable to a commercial model for manufacture.