PROJECT SUMMARY/ABSTRACT There is a need for improved monitoring tools for the brain in TBI patients. Survivors of severe brain injuries may require care in an intensive care unit (ICU), where the brain is vulnerable to secondary brain injuries, defined by a mismatch between the metabolic supply and demand that creates ischemia. Existing technologies for monitoring secondary brain injuries are inadequate: continuous scalp EEG is noninvasive and detects seizures, but only indirectly reflects cerebral blood flow compromise. In some cases, invasive probes are placed within the brain to detect cerebral blood flow and brain tissue oxygenation directly. However, this strategy can be risky and only monitors a small region of the brain. Thus, there is a need for real-time, noninvasive, multimodal measurements of the brain’s electrical activity, oxygenation, and hemodynamics in humans. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data on brain activity and function. EEG records the brain’s local electrical field potentials with exquisite temporal resolution. Optical imaging uses low- intensity light to quantify cerebral blood flow (CBF) and cerebral oxygen saturation (StO2). In Aim 1, we will adapt our DCS current instrument for continuous for longitudinal monitoring of TBI patients alongside to clinical instruments. In Aim2, we will perform a validation study to evaluate this new, integrated, noninvasive technology by comparing directly with the gold standard, FDA-approved invasive measurement of brain blood flow and oxygenation in patients with TBI undergoing clinically-standard invasive monitoring. This study will lead directly to further device development and investigational device application, with a goal for a device that will allow for brain blood flow and oxygenation monitoring in all patients with acute brain injuries in order to guide management.