PROJECT SUMMARY The Brimrose Technology Corporation and partner, The Johns Hopkins University, propose using non-invasive ultrasound neuromodulation to identify hypoxic-ischemic encephalopathy (HIE) in newborns to reduce death and lifelong brain injury. HIE is the leading cause of neonatal death and impacts 2-6 of every 1,000 live births in the developed world. Our goal is to investigate and demonstrate the effect of graded hypoxia and repeated oxygen/glucose deprivation on neural response using ultrasound modulation. We will then develop and validate an ultrasound-neuromodulation coupled with photoacoustic-imaging device prototype to monitor neonatal brain injury. This device will be used for early diagnosis of HIE to enable timely intervention, which minimizes long-term disability. The two organizations have established a strong research team and joint operating lab at Hopkins to develop this system. Due to various limitations of current methods, there is an urgent need for an early HIE diagnostic kit to enable prompt therapeutic interventions. There are no early diagnostic procedures or devices available in the clinic for HIE. Hence, our proposal addresses a critical unmet need.