Development of quantitative optical tools to continuously monitor cerebral autoregulation, blood flow, oxygenation and inflammation during pediatric extracorporeal life support

开发定量光学工具，在儿科体外生命支持过程中持续监测脑自动调节、血流、氧合和炎症

• 批准号: 10365859
• 负责人: David Richard Busch
• 金额: $ 68.25万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365859
• 关键词: Acids; Adult; Biological Assay; Biological Markers; Blood; Blood Pressure; Blood flow; Blood specimen; Brain; Cardiopulmonary Bypass; Cerebrovascular Circulation; Cerebrum; Cessation of life; Child; Childhood; Clinical; Critical Illness; Critically ill children; Development; Diffuse; Disease; Extracorporeal Membrane Oxygenation; Family; Financial cost; Future; Goals; Heart; Hemorrhage; Homeostasis; Hour; Image; Immunotherapy; Impairment; Inflammation; Inflammatory; Injury; Intervention; Knowledge; Lead; Life; Limes; Lung; Measurement; Measures; Mediator of activation protein; Methods; Monitor; Morbidity - disease rate; Neonatal; Nervous System Trauma; Neurologic; Neurologic Deficit; Nursery Schools; Optics; Outcome; Pathway interactions; Patients; Perfusion; Pilot Projects; Population; Protocols documentation; Quality of life; Research; Risk; Savings; School-Age Population; Scientist; Secondary to; Societies; Spectrum Analysis; Speed; Survivors; Systemic blood pressure; Testing; Time; TimeLine; Titrations; Up-Regulation; Work; base; blood lead; brain health; cohort; conventional therapy; cytokine; healing; healthy aging; high risk; indexing; insight; ischemic injury; mortality; neonatal patient; neurobehavioral; neuroinflammation; novel; pediatric patients; point of care; prevent; prospective; protocol development; recruit; temporal measurement; tool

Extracorporeal Membrane Oxygenation (ECMO) is a form of cardiopulmonary bypass which provides days to weeks of life-saving support to critically ill children and adults whose illness is progressing despite maximal conventional therapies. Use of ECMO is expanding rapidly and it has supported >71,000 children worldwide. Advances in ECMO have allowed more children to survive an otherwise fatal illness, however neurological injury reduces survival by 50-60% and leads to significant long-term neurologic morbidity. Only half of ECMO survivors have normal neurobehavioral outcomes. The underlying disease and ECMO may both disrupt cerebral autoregulatory mechanisms and cause neuroinflammation, which may also disrupt autoregulation. Disrupted cerebral autoregulation predisposes the brain to hemorrhagic or ischemic injury via excessive or inadequate perfusion, yet it is not monitored during ECMO. Current clinical tools do not predict neurological injury, greatly inhibiting the development of neuroprotective protocols. Specifically, there is no monitor to continuously assess the state of cerebral autoregulation, forcing clinicians to rely on imperfect systemic surrogates that may not reflect risks of impending neurological injury. The long-term goal of this research is to develop continuous non-invasive bedside monitors for critically ill patients. The primary goals of this proposal are to (1) test the hypothesis that continuous point-of-care optical monitoring of cerebral autoregulation can predict neurologic injury after the first 48 hours of ECMO and (2) demonstrate that optically measured indices of cerebral autoregulation are associated with neuroinflammatory biomarkers in serial blood samples throughout ECMO. A pilot study led by the Pl has demonstrated the feasibility of using advanced non-invasive optical monitors to assess cerebral autoregulation and cerebral perfusion in pediatric ECMO patients. Our ongoing pilot study has shown disrupted autoregulation indices correlate with neurological injury found on post-ECMO imaging. This proposal will utilize diffuse optics to longitudinally monitor cerebral autoregulation and inflammation throughout ECMO in a large pediatric population (0-18 y.o., n=125). In Aim 1, we will demonstrate that alterations in optical metrics of cerebral autoregulation during ECMO predict neurological injury found on intra-ECMO CT. In Aim 2, we will demonstrate that optical metrics of cerebral autoregulation measure the temporal course of neuroinflammation, as evidenced by biomarkers in lab-based blood assays. If successful, the work of this interdisciplinary team of physical scientists, clinicians, and neuroscientists will establish the value of continuous quantitative optical monitoring of cerebral autoregulation to prospectively identify periods of high risk of injury during ECMO. These results will enable the development of brain-focused cardio-pulmonary bypass protocols (e.g., blood pressure titration) to reduce the rate of neurologic injury and associated mortality and morbidity in ECMO patients.

体外膜氧合（ECMO）是一种心肺旁路的形式，可提供天数 至今仍有生命疾病的儿童和成年人的生命支持数周 常规疗法。 ECMO的使用正在迅速扩展，并且在全球范围内为71,000名儿童提供了支持。 ECMO的进步使更多的孩子能够生存在原本致命的疾病中，但是神经系统 损伤将存活率降低了50-60％，并导致显着的长期神经系统发病率。 ECMO的一半 幸存者具有正常的神经行为结局。潜在的疾病和ECMO可能会破坏 大脑自调机制并引起神经炎症，这也可能破坏自动调节。 脑自动调节破坏使大脑易出血或缺血性损伤 灌注不足，但在ECMO期间未经监测。当前的临床工具无法预测神经系统 受伤，极大地抑制了神经保护方案的发展。具体来说，没有监视器 不断评估脑自动调节状态，迫使临床医生依靠不完善的系统性 可能无法反映即将发生神经损伤的风险的代理。 这项研究的长期目标是开发持续的非侵入性床头监视器，以使重病 患者。该提案的主要目标是（1）检验以下假设，即连续护理光学的光学 脑自动调节的监测可以预测ECMO的最初48小时后的神经系统损伤和（2） 证明脑自动调节的光学测量指标与神经炎症有关 整个ECMO的系列血液样本中的生物标志物。 PL领导的一项试点研究证明了 使用先进的非侵入性光学监测仪评估脑自动调节的可行性 小儿ECMO患者的脑灌注。我们正在进行的试点研究显示 自动调节指数与ECMO后成像上发现的神经损伤有关。该建议将使用 扩散光学器件可纵向监测整个ECMO的大脑自动调节和炎症 小儿种群（0-18 Y.O.，n = 125）。在AIM 1中，我们将证明光学指标的变化 ECMO期间的脑自动调节预测ECMO内CT上发现的神经系统损伤。在AIM 2中，我们将 证明脑自动调节的光学指标衡量神经炎症的时间过程， 基于实验室的血液测定中的生物标志物证明了这一点。 如果成功的话，这个身体科学家，临床医生和神经科学家的跨学科团队的工作将会 确定对脑自动调节的连续定量光学监测的价值 确定ECMO期间高伤害风险的时期。这些结果将使以脑为中心的发展 心肺旁路方案（例如，血压滴定），以降低神经系统损伤和 ECMO患者的相关死亡率和发病率。