Cerebral autoregulation and MRI measures of brain injury after pediatric-post cardiac arrest

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PROJECT ABSTRACT Pediatric cardiac arrest is common, with resultant high morbidity and mortality. Neurologic disability occurs in up to 80% of children who survive a cardiac arrest. Brain injury after cardiac arrest is caused by the initial hypoxic-ischemic event and from secondary brain injury that occurs in the following hours to days. The focus of post-cardiac arrest care is to reduce secondary brain injury. Cerebral autoregulation (CAR) is a physiologic process by which cerebral blood vessels dilate or constrict to maintain relatively constant cerebral blood flow (CBF) across a range of mean arterial blood pressures (MAPs). Impaired CAR makes the brain vulnerable to states of hypoperfusion and hyperperfusion which can contribute to secondary brain injury and preventable neurologic disability. There is a knowledge gap regarding the MAP at which CAR is most intact after pediatric cardiac arrest, and the impact of the deviation from this optimal MAP on brain injury and clinical outcomes. The central hypothesis of this proposal is that patients with larger differences between their MAP and optimal MAP after cardiac arrest will have worse microstructural brain injury and clinical outcomes. For this proposal, CBF will be measured directly using an advanced, non-invasive optical imaging technique called diffuse correlation spectroscopy (DCS), which will be used to calculate optimal MAP. Brain injury will be quantified using diffusion magnetic resonance imaging (MRI). The primary clinical outcome is neurologic disability at hospital discharge based on the Pediatric Cerebral Performance Category. The objectives of the proposed research are to determine whether patients with larger deviations from their DCS- determined optimal MAP have worse clinical outcomes (Aim 1) and microstructural brain injury on diffusion MRI (Aim 2) compared to patients with smaller deviations from their optimal MAP. In addition, regional CBF derived from DCS will be correlated with CBF derived from arterial spin labeled (ASL) MRI (Aim 3). The successful completion of these studies will further our understanding of the mechanisms underlying post-cardiac arrest brain injury and inform future trials of cerebral physiology-targeted management strategies to improve pediatric cardiac arrest outcomes. The applicant, Dr. Matthew Kirschen, a pediatric intensivist and neurologist at the Children’s Hospital of Philadelphia and University of Pennsylvania, will engage in a rigorous training program of didactic courses and mentoring by experts in pediatric cardiac arrest, cerebral physiology and autoregulation, and brain imaging. He will gain expertise in clinical biostatistics through the Master of Science in Clinical Epidemiology program, advanced optical imaging, and diffusion MRI analytics. Through the proposed studies, his parallel career development plan, a team of dedicated and experienced mentors, and a world-class environment, Dr. Kirschen will achieve his goal of becoming an independent neurocritical care research scientist with special focus on neurologic resuscitation following pediatric cardiac arrest.