Diffuse Optical Tomography for Identifying Early Complicationsof Aneurysmal Subarachnoid Hemorrhage

项目摘要/摘要 动脉瘤性蛛网膜下腔出血(ASAH)的死亡率超过30%。适用于以下患者 在最初的出血中幸存下来，他们的临床过程充满了并发症，包括脑积水， 癫痫发作、脑水肿、血管痉挛和迟发性脑缺血。ASAH患者的临床监测， 然而，精神状态的改变和不能完全参与床边活动经常使患者感到困惑 神经学检查，可能阻碍出血后并发症的早期诊断。有能力 确定ASAH后神经并发症的早期生物标志物将是一个重要的进展 目前对ASAH患者的护理标准。 从长远来看，ASAH幸存者患有认知缺陷，这种缺陷与 功能连接(FC)。在动物模型SAH后，Fc迅速发生变化，并可能反映急性 损伤，但仍不清楚FC的变化是否与人类受试者的急性神经功能下降有关。 此外，皮质扩散性去极化(CSD)也被认为是神经疾病的一种病因。 ASAH术后并发症。CSD是一种组织去极化波，它会大量改变离子梯度， 有助于兴奋毒性和脑水肿，并影响局部血管系统。使用侵入性硬膜下 已经在ASAH患者中观察到电极、CSD，并且CSD事件簇与延迟相关 缺血性脑梗塞。然而，CSD的非侵入性检测并不存在。 这项建议将利用高密度漫反射光学断层扫描(DOT)来监测ASAH患者以测试 假设CSD和静息状态FC的变化可以预测神经功能下降。点度量度 氧合和脱氧血红蛋白光吸收的变化。Dot已用于监控Fc中的休眠状态 中风患者和可用于检测慢性阻塞性肺疾病。DOT作为一种监测方法的一个优点是它可以 用于ICU的床边并用于纵向检查，不同于基于MRI的方法 仅限于离散成像时期，危重患者不易接触到。目标1将测试 假设神经恶化与静息状态Fc的变化相关。AIM 2将测试 ASAH后的CSD是否与神经学检查的急性恶化相关。 该项目的结果将确定ASAH后FC改变和CSD事件是否可以作为生物标记物 用于治疗ASAH患者的神经功能下降。这些生物标志物的长期影响包括 氯胺酮或迷走神经阻断CSD等ASAH并发症的干预和治疗 刺激，和/或使用FC变化来指导康复。此外，CSD的无创检测与 DOT为其他神经系统疾病的CSD研究提供了一种突破性的方法。

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.