Diffuse Optical Tomography for Identifying Early Complicationsof Aneurysmal Subarachnoid Hemorrhage

弥漫性光学断层扫描识别动脉瘤性蛛网膜下腔出血的早期并发症

• 批准号: 10723095
• 负责人: Anja Iwona Srienc
• 金额: $ 8.19万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10723095
• 关键词: Acute; Affect; Aneurysmal Subarachnoid Hemorrhages; Animal Model; Bilateral; Biological Assay; Biological Markers; Brain; Caring; Cerebral Edema; Cerebral Ischemia; Characteristics; Clinical; Cognitive deficits; Critical Illness; Deterioration; Diagnosis; Drops; Early Diagnosis; Early Intervention; Early identification; Early treatment; Edema; Effectiveness; Electrodes; Etiology; Event; Frequencies; Glasgow Coma Scale; Grant; Hemoglobin; Hemorrhage; Hour; Hydrocephalus; Image; Image Analysis; Imaging Techniques; Impaired cognition; Infarction; Injury; Intervention; Investigation; Ions; Ischemia; Ketamine; Life; Light; Link; Magnetic Resonance Imaging; Measures; Metabolic; Methods; Migraine; Monitor; Mus; Nerve; Nervous System Physiology; Neurologic; Neurons; Non-Invasive Detection; Patients; Pattern; Phase; Prognosis; Recovery; Recurrence; Rehabilitation therapy; Rest; Role; Scanning; Seizures; Severities; Signal Transduction; Stroke; Survivors; System; Taxes; Testing; Therapeutic Intervention; Time; Tissues; Traumatic Brain Injury; Vasospasm; Work; absorption; biomarker identification; clinical biomarkers; clinical care; cognitive function; cohort; density; deoxyhemoglobin; detection method; diffuse optical tomography; early detection biomarkers; excitotoxicity; experience; human subject; imaging modality; improved; indexing; mental state; mortality; nervous system disorder; neuron loss; non-invasive monitor; novel; prevent; research clinical testing; standard of care; stroke patient; tool

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.

项目总结/摘要 动脉瘤性蛛网膜下腔出血（aSAH）的死亡率超过30%。的患者 在最初的出血中存活下来，他们的临床过程充满了并发症，包括脑积水， 癫痫、脑水肿、血管痉挛和迟发性脑缺血。aSAH患者的临床监测， 然而，经常被精神状态的改变和无法充分参与床边治疗所混淆。 神经系统检查，可能妨碍出血后并发症的早期诊断。的能力 确定aSAH后神经系统并发症早期生物标志物将是一个重要的进展， 目前aSAH患者的护理标准。 从长远来看，aSAH幸存者患有认知缺陷，这与以下改变相关： 功能连通性（FC）。在动物模型中，蛛网膜下腔出血后FC的变化迅速发生，可能反映了急性 损伤，但仍然不清楚FC的变化是否与人类受试者的急性神经功能下降相关。 此外，皮层扩展性去极化（CSD）也被认为是神经系统性脑损伤的病因。 aSAH后的并发症CSD是一种组织去极化波，它会极大地改变离子梯度， 导致兴奋性毒性和脑水肿，并影响局部脉管系统。使用侵入性硬膜下 在aSAH患者中已经观察到CSD，并且CSD事件的集群与延迟的 缺血性梗塞然而，不存在CSD的非侵入性检测。 该提案将利用高密度扩散光学断层扫描（DOT）监测aSAH患者，以检测 CSD和静息状态FC的变化可以预测神经功能衰退的假说。DOT措施 氧合血红蛋白和脱氧血红蛋白的光吸收变化。DOT已用于监测静息状态FC， 脑卒中患者，可用于检测CSD。DOT作为监测方法的一个优点是， 在ICU的床边使用，并用于纵向调查，不像基于MRI的方法， 局限于离散的成像时期，并且不容易被危重患者接近。目标1将测试 假设神经功能恶化与静息状态FC的变化相关。目标2将测试 aSAH后CSD是否与神经系统检查的急性恶化相关。 本项目的结果将确定aSAH后FC改变和CSD事件是否可作为生物标志物 用于aSAH患者的神经功能下降。这些生物标志物的长期影响包括早期 aSAH并发症的干预和治疗，如用氯胺酮或迷走神经阻断CSD 刺激和/或使用FC变化来指导康复。此外，CSD的非侵入性检测， DOT将为研究CSD在其他神经系统疾病中的作用提供一种突破性的方法。