Abstract Monitoring intracranial pressure (ICP) and treating elevations in ICP to maintain adequate cerebral blood flow (CBF), is the recommended standard of care following severe traumatic brain injury (TBI). ICP is measured by a small pressure-sensitive probe inserted through the skull, with risk of intracranial hemorrhage and infection, hence used only in comatose patients. The ability to monitor ICP non-invasively would improve global access to ICP monitoring, allow for faster and more effective triage of trauma patients, extend ICP monitoring to patients whose risk may be substantial but not enough to justify the invasive procedure. Transcranial Doppler ultrasound (TCD), the current leading non-invasive alternative to invasive ICP monitors, is not sufficiently accurate, requires specialized operators and is impractical for continuous monitoring. In this context, diffuse correlation spectroscopy (DCS) a near-infrared diffuse optical method, has emerged as a promising alternative to estimate ICP from the critical closing pressure (CrCP, the arterial blood pressure at which brain vessels collapse and cerebral blood flow ceases) or the morphology of the pulsatile cerebral blood flow signal (pCBF). The main barrier for widespread adoption of DCS for ICP measurements is the low signal to noise ratio (SNR) of currently available technology, which limits source-detector separation to 2.5 cm, offering relatively low brain sensitivity and strong scalp contamination, and requires pulse-gated averages of 50-60 cardiac cycles to extract clean pCBF waveforms, compromising the morphological information. Building on our expertise and on our preliminary results, we propose to develop a novel speckle contrast optical spectroscopy (SCOS) device, featuring pulsed- laser sources and heterodyne detection, able to assess pCBF at 3.5 cm and 50 Hz with superior SNR (>100 x gain over DCS). Moreover, we plan to integrate the SCOS device with our recently developed wearable near- infrared spectroscopy (NIRS) device (FlexNIRS), which, by synergistically operating between SCOS camera frames, will simultaneously measure pulsatile blood volume. As shown in our preliminary results and a recent publication, the simultaneous measure of pulsatile blood flow and volume will allow separation of arterial inflow and venous outflow, and further enhance pCBFi SNR and sampling rate, which, we hypothesize will improve ICP estimation accuracy. Finally, the integration of SCOS and FlexNIRS will provide additional important biomarkers to monitor brain health status on TBI patients, i.e., hemoglobin oxygenation, changes in cerebral blood flow, hemoglobin concentration and oxygen consumption, cerebrovascular resistance, and cerebral autoregulation.. The successful realization of this state-of-the-art, non-invasive cerebral monitor will have a transformative role in neurocritical care, especially in low resource and rural settings, by expanding access to ICP monitoring and providing new mo...