PROJECT SUMMARY/ABSTRACT The lack of a noninvasive, cost-effective, and highly accessible technology for monitoring cerebral metabolic rate of oxygen (CMRO2) poses a critical gap in neurology and brain health. Current methods, including positron emission tomography, functional magnetic resonance imaging, diffuse optical tomography, and catheter-based jugular venous oxygen saturation monitoring, have limitations such as radiation exposure, invasiveness, limited spatial and temporal resolution, and reduced accessibility. This project aims to address this unmet need by developing the next-generation photoacoustic computed tomography through an ergodic relay (PACTER) device for noninvasive CMRO2 monitoring. In Aim 1, the device will be designed and fabricated to enable high-resolution vascular imaging of oxygen metabolism. This will involve integrating an acoustic impedance-matching layer, using longer-wavelength illumination for improved spatial resolution and penetration depth for imaging the carotid artery and internal jugular vein, and employing dual-wavelength illumination for quantifying total hemoglobin concentration and oxygen saturation. Additionally, blood flow will be measured using photoacoustic vector tomography. The device will be customized for handheld operation, ensuring easy access to imaging regions. In Aim 2, the next-generation PACTER device will be characterized and validated for monitoring CMRO2 in humans. Imaging performance, accuracy, and sensitivity will be assessed using tissue-simulating phantoms, animal models, healthy volunteers, and patients with neurological conditions. By measuring relevant parameters in the carotid artery and internal jugular vein, including blood volume, hemoglobin concentration, oxygen saturation, and blood flow, the device will enable the calculation of oxygen extraction and CMRO2. Comparisons with existing methods, such as fMRI, will be conducted, setting the stage for future clinical validation studies. The proposed research addresses the significant gap in noninvasive CMRO2 monitoring and offers transformative advancements. The development of the next-generation PACTER device will facilitate personalized diagnostics and care for neurology, neurosurgery, and critical care patients. It will provide timely and crucial information for accurate diagnosis, treatment guidance, and surgical decision-making, ultimately leading to improved medical outcomes and quality of life. Furthermore, the cost-effectiveness and accessibility of PACTER will contribute to reducing the overall cost of medical care and benefit researchers in the field. The project's innovation lies in the creation of a highly accessible device with label-free, non-ionizing, and high-spatiotemporal-resolution imaging capabilities, overcoming the limitations of current CMRO2 monitoring techniques. In summary, the next- generation PACTER device offers a novel approach to noninvasive CMRO2 monitoring, addressing a critical gap in the field....