Prospective Identification of Hypoxic Ischemic Brain Injury Using Portable Magnetic Resonance Imaging

PROJECT SUMMARY The largest determinant of survival and good neurologic outcomes in patients successfully resuscitated after cardiac arrest (CA) is the burden of hypoxic-ischemic brain injury (HIBI), a result of both the primary anoxic event and accrual of secondary brain injury. Mitigating secondary brain injury is critical to improving neurologic outcomes in this devastating disease. The lack of early, deployable biomarkers to phenotype CA patients has stifled advancements in therapeutics. Conventional high-field MRI is a guideline recommended component of neuroprognostication. A diffuse pattern of restricted diffusion on MRI is a reliable predictor of severe HIBI and functional dependence. Lack of access to MRI amongst critically ill CA survivors has led to underutilization, hindering the development of imaging-based biomarkers and intermediate endpoints. Low-field portable MRI costs a fraction of high-field MRI, is FDA approved, does not require magnetic shielding, and can be deployed in the emergency department and intensive care unit without disruption of vital patient monitoring. The proposed protocol will provide the scientific community with the largest systematically ascertained prospective observational cohort of low-field portable MRI in CA patients. To ensure the acquisition of clinically useful images, in agreement with conventional high-field MRI, we will evaluate the inter-rater agreement of low-field and high-field MRI for the evaluation of HIBI in 60 participants. Parallel to this, we will acquire ultra early (≤ 6 hours) and early (12-24 hours) low- field portable MRI to establish the positive predictive value and specificity of diffusion weighted imaging lesions for predicting HIBI on conventional MRI. Unlike focal ischemia, global ischemia, as seen in HIBI, progresses over days and may result in delayed apparent diffusion coefficient signal changes. Low-field portable MRI provides a unique opportunity to evaluate the time- dependent nature of HIBI on MRI. The development of early MRI-based HIBI biomarkers requires firm knowledge of the temporal and spatial variability of HIBI, including identification of early findings that persist on delayed imaging. This proposal is the first step towards developing a novel neuroimaging tool, low-field portable MRI, to understand HIBI mechanisms, therapeutic targets, and prognosis in patients resuscitated from CA.