Diffuse Optical Tomography for Identifying Early Complicationsof Aneurysmal Subarachnoid Hemorrhage

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PROJECT SUMMARY/ABSTRACT Aneurysmal subarachnoid hemorrhage (aSAH) carries a mortality rate greater than 30%. For patients who survive the initial hemorrhage, their clinical course is fraught with complications including hydrocephalus, seizures, cerebral edema, vasospasm, and delayed cerebral ischemia. Clinical monitoring of aSAH patients, however, is often confounded by altered mental status and inability to fully participate in the bedside neurological exam, potentially impeding the early diagnosis of post-hemorrhagic complications. The ability to identify early biomarkers of neurological complications after aSAH would be an important advance in the current standard of care of aSAH patients. In the long-term, aSAH survivors suffer from cognitive deficits that have been correlated with alterations in functional connectivity (FC). Changes in FC occur rapidly after SAH in animal models and may reflect acute injury, but it remains unknown if FC changes correlate with acute neurological decline in humans subjects. Additionally, cortical spreading depolarization (CSD) has also been implicated as an etiology of neurological complications after aSAH. CSD is a wave of tissue depolarization that massively alters ion gradients, contributes to excitotoxicity and cerebral edema, and affects local vasculature. Using invasive subdural electrodes, CSD’s have been observed in aSAH patients, and clusters of CSD events correlate with delayed ischemic infarctions. However, noninvasive detection of CSD does not exist. This proposal will utilize high density diffuse optical tomography (DOT) to monitor aSAH patients to test the hypotheses that CSD and changes in resting state FC can predict neurological decline. DOT measures changes in light absorption of oxy- and deoxy-hemoglobin. DOT has been used to monitor resting state FC in stroke patients and can be used to detect CSD. One advantage of DOT as a monitoring method is that it can be used at the bedside in the ICU and used for longitudinal investigation, unlike MRI-based methods which are limited to discrete imaging epochs and are not easily accessible to critically ill patients. Aim 1 will test the hypothesis that neurological deterioration correlates with a changes in resting state FC. Aim 2 will test whether CSD after aSAH correlates with acute worsening of the neurologic exam. The results of this project will establish if FC alterations and CSD events after aSAH can serve as biomarkers for neurological decline in aSAH patients. The long-term implications of such biomarkers include earlier interventions and treatments of aSAH complications, such as blocking CSD with ketamine or vagal nerve stimulation, and/or using FC changes to guide rehabilitation. Additionally, noninvasive detection of CSD with DOT would provide a breakthrough method to study CSD in other neurological conditions.