Non-Invasive Multi-Modal Neuromonitoring in Adults Undergoing Extracorporeal Membrane Oxygenation

PROJECT SUMMARY Extracorporeal membrane oxygenation (ECMO) is a last resort procedure for patients with acute heart or lung failure. The procedure carries significant risk of brain injury, yet no brain monitoring is performed, partly due to significant risks of current neuroimaging technologies. Thus, the cause of these injuries, their relation with ECMO settings, and how they can be prevented are unknown. A critical need exists for non-invasive techniques to mon- itor brain physiology at the bedside for ECMO patients and for strategies to minimize brain injury. Our objective is to develop a means to find predictors of neurologic functional outcome based on severity of injury assessment in ECMO patients that can potentially lead to individualized optimization of extracorporeal support and timely neuroprotective interventions. To this end, we have carefully selected multi-modal monitoring techniques that can quantify cerebral autoregulation, neurovascular coupling, and neuronal health. To probe cerebral autoreg- ulation based on microvascular blood flow, diffuse correlation spectroscopy (DCS) will be used. Near-infrared spectroscopy (NIRS) will provide blood oxygenation and volume information. Electroencephalogram (EEG) will measure cortical electrical activity continuously, and evoked potentials (EPs) will measure the functionality of subcortical nuclei in the brainstem and midbrain. We hypothesize that this combination will enable prediction of functional outcome in patients undergoing ECMO. Furthermore, simultaneous measurements of hemodynamic and electrophysiological parameters will provide a unique opportunity to investigate disruption of neurovascu- lar coupling as an additional marker for brain injury. In Aim 1, we will construct several prediction models for functional outcome based on multi-modal neuromonitoring parameters from ECMO patients and evaluate their capabilities. In Aim 2, we will investigate whether our inter-hemispheric asymmetry measure of cerebral au- toregulation, developed during preliminary studies, is a unique marker for ECMO by comparing patients with and without ECMO treatment. In Aim 3, we will construct a new low-cost optical system and carefully validate against established DCS and NIRS system. The new system will enable continuous monitoring for future multi-center trials and multi-regional measurements. Successful completion of these aims will result in great advances in ECMO and neurology research by provid- ing a comprehensive innovative non-invasive longitudinal monitoring tool. In terms of ECMO, this work lays the foundation for using this tool to optimize ECMO settings and reduce the occurrence of brain injuries in critically-ill patients. Broadly, this multi-modal tool can be used to understand how the brain functions in diseased states in order to discover treatments to prevent and treat neurologic disorders.