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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要动脉瘤性蛛网膜下腔出血 (aSAH) 的患者死亡率超过 30%。在最初的出血中幸存下来，他们的临床病程充满了并发症，包括脑积水， aSAH 患者癫痫发作、脑水肿、血管痉挛和迟发性脑缺血的临床监测。然而，经常因精神状态改变和无法充分参与床边工作而感到困惑神经系统检查，可能妨碍出血后并发症的早期诊断。识别 aSAH 后神经系统并发症的早期生物标志物将是一个重要的进步目前 aSAH 患者的护理标准。从长远来看，aSAH 幸存者会遭受认知缺陷，这与认知功能的改变有关。动物模型中 SAH 后功能连接 (FC) 迅速发生变化，可能反映了急性症状。损伤，但 FC 变化是否与人类受试者的急性神经功能衰退相关仍不清楚。此外，皮质扩散去极化（CSD）也被认为是神经系统疾病的病因之一。 aSAH 后的并发症是组织去极化波，会极大地改变离子梯度，导致兴奋性中毒和脑水肿，并影响局部脉管系统。在 aSAH 患者中观察到 CSD，并且与延迟相关的 CSD 事件簇然而，目前尚不存在 CSD 的无创检测。该提案将利用高密度扩散光学断层扫描 (DOT) 监测 aSAH 患者，以测试假设 CSD 和静息状态 FC 的变化可以预测 DOT 测量值。 DOT 已用于监测静息态 FC。 DOT 作为一种监测方法的一个优点是它可以对中风患者进行检测。与基于 MRI 的方法不同，可在 ICU 床边使用并用于纵向研究仅限于离散成像时期，并且危重患者不易获得，目标 1 将测试该方法。目标 2 将测试神经功能恶化与静息状态变化相关的假设。 aSAH 后的 CSD 是否与神经系统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志物对于 aSAH 患者的神经功能衰退，此类生物标志物的长期影响包括早期。 aSAH 并发症的干预和治疗，例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，还有 CSD 的无创检测。 DOT 将为研究其他神经系统疾病中的 CSD 提供突破性方法。