Project Summary The objective of PREcision Care In Cardiac ArrEst - ICECAP (PRECICECAP) is to discover novel biomarker signatures of post cardiac arrest brain and extracerebral organ failure that predict treatment responsiveness and long-term recovery. We will achieve this by partnering with the ICECAP trial, a response-adaptive dose finding clinical research trial that seeks to determine the optimal duration of post-arrest hypothermia. Cardiac arrest is a major public health problem with high morbidity and mortality. Four in five patients hospitalized after cardiac arrest have significant brain injury, and death from neurologic damage is common. Improving survival and functional recovery is a critical public health objective and will require innovative approaches. The current clinical situation is unprecedented. Currently post-CA brain injury is an acute, sudden critical illness with major knowledge gaps about how best to characterize severity of injury and to identify which individual patients are likely to benefit from specific neuroprotective strategies. Thus, development of high- performing biomarker signatures is a critical need and would translate in to immediate changes in care. We hypothesize that not all patients are identical (i.e. there will be a heterogeneity of treatment effect) and that through our innovative, multi-parametric data driven approach, we will be able to identify novel signatures that define subgroups of patients. Advanced data science and analytical approaches will allow the identification of these subgroups that was previously not possible. These subgroups will be clinically important insofar as they will indicate differential responses to treatment and different trajectories of functional recovery. This project will acquire high resolution multi-modal data early in the disease course that will allow us to address these current knowledge gaps and improve our understanding of the disease in the early acute setting when interventions can improve outcome. The knowledge learned here will be applied to develop personalized treatments for cardiac arrest survivors, addressing the NIH's and our goals of lengthening life and reducing disability.