PROJECT SUMMARY Continuous intracranial pressure (ICP) monitoring is an important surveillance tool for critically ill neurologic patients that provides critical insights on disease severity for guiding medical management . However, ICP monitoring requires a highly invasive procedures that incurs risks for intracranial hemorrhage and infection.24–28 Thus, the clinical indications for ICP monitoring are a topic of debate and up to 50% of traumatic brain injury patients who fulfill recommendation criteria for an ICP monitor never receive it.22 Moreover, nearly half of patients admitted to the Neuro-Intensive Care Unit (Neuro-ICU) without an ICP monitor go on to later develop elevated ICP.1 Unfortunately, even eligible patients are only provided ICP monitoring while in the Neuro-ICU. After adequate recovery, they are transferred to a step-down unit without a monitor even though they are still at high risk for developing elevated ICPs and potentially fatal brain herniation. Therefore, there is a clear unmet need for a non-invasive approach to continuous ICP monitoring. We propose to develop a non-invasive sensing system to continuously monitor ICP by correlating beat- to-beat carotid artery BP to ICP. Prior studies have demonstrated that central aortic waveforms detected at the extracranial portion of the carotid artery closely resemble ICP waveforms.3-10 In our previous work, we developed highly sensitivity conformal sensors capable of measuring carotid artery BP waveforms with minimal applanation pressure. 36,37 W e have also demonstrated a novel pressure estimation algorithm that can sustain high accuracy radial artery BP measurements in surgical and ICU patients. 13 By combining our highly sensitive sensors with our generalizable pressure estimation algorithm, we hypothesize that we can non-invasively and continuously monitor ICP by developing a parameter estimation model to correlate our sensor's carotid BP measurements with ICP waveforms using recordings from Neuro-ICU patients for training and validation . Studies have also demonstrated the clinical utility of other ICP waveform-derived indices for assessing intracranial compliance and prognosticating patient outcomes.14–18 Due to the morphological similarity between carotid BP and ICP waveforms, we hypothesize that these waveform features can also be applied to our carotid BP measurements and sensor-derived ICP estimations to gain unique insights on patient neurologic status that can aid medical decision-making. T he findings of this project have the potential to form the basis for future investigations on utilizing the waveform features of carotid BP as a proxy measure of ICP. Moreover, i f successful, our proposed non-invasive, continuous ICP monitor has the potential to not only enhance neurologic monitoring across a broader range of patients, but also create a paradigm shift in existing clinical protocols in favor of more proactive ICP surveillance.