Brain Monitoring and Therapeutic Hypothermia after Cardiac Arrest

心脏骤停后的脑部监测和低温治疗

• 批准号: 8831135
• 负责人: Xiaofeng Jia
• 金额: $ 37.61万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8831135
• 关键词: Affect; Algorithms; Animals; Area; Arousal; Biological Markers; Blood Glucose; Brain; Brain Injuries; Brain region; Categories; Cerebrum; Clinical; Coma; Consumption; Development; Electroencephalography; Entropy; Evaluation; Evolution; Experimental Models; External Defibrillator; Feedback; Frequencies; Glucose; Goals; Health; Heart; Heart Arrest; Histology; Image; Injury; Measures; Metabolic; Metabolism; Methodology; Methods; Monitor; Neurologic; Neurological outcome; Outcome; Patient Monitoring; Pattern; Phase; Play; Positron-Emission Tomography; Procedures; Recovery; Recovery of Function; Resuscitation; Role; Signal Transduction; Survivors; Synapses; Temperature; Testing; Thalamic structure; Therapeutic; Therapeutic Effect; Time; Titrations; Translations; base; clinical practice; functional outcomes; glucose metabolism; improved; induced hypothermia; innovation; natural hypothermia; neurological recovery; neuroprotection; novel; prevent; prognostic; protective effect; response; response to injury; restoration; sudden cardiac death; tool

DESCRIPTION (provided by applicant): More than 400,000 sudden cardiac deaths occur in the USA annually. Among survivors of cardiac arrest (CA), brain injury is the biggest impediment to functional recovery. Induced hypothermia is currently the only form of therapy that improves both survival and neurological outcome for CA survivors. However, for decades, hypothermia delivery has been blindly directed toward faster cooling, and without objective indicators of the brain's response to temperature. So far, there is no monitoring methodology to guide hypothermia therapy and to improve its efficiency. A major hindrance for more beneficial results of this therapy is that optimal level and duration of hypothermia is unknown. The detail mechanisms underlying the protective effect of hypothermia are also largely unknown. Aim 1: Our first goal is to develop and evaluate novel, non-invasive, quantitative EEG (qEEG) marker of functional outcome after CA. We test the hypotheses that a) qEEG analysis, based on our novel entropy based algorithms, will capture electrophysiological recovery to pre-CA baseline, and b) sequential recovery in subbands will have highly differentiated entropy level, and correspondingly show greater sensitivity to different phases of recovery after injury and effects of therapeutic hypothermia. Aim 2: We will use the qEEG marker to obtain feedback on brain's response to the a) depth (temperature level) and b) duration of hypothermia delivery. We will test the hypothesis that electrophysiological monitoring by qEEG will serve as a biomarker of the brain's recovery and, thus, will provide objective guidance for hypothermia delivery. Aim 3: Our last broad goal is to provide an objective analysis of hypothermia's effect on spatio-temporal pattern of glucose utilization (via small animal positron emission tomography (PET) imaging and electrophysiological recovery (EEG)) after CA. We test the hypotheses that hypothermia will increase the glucose re-utilization and change the spatial pattern in subcortical and cortical brain regions, which contribute to corresponding EEG changes signaling recovery with an earlier return of normalization, to improve the functional outcome after CA. The significance of this project is three fold: 1) development and systematic evaluation of simple and objective qEEG monitoring tools of brain injury after CA, 2) the expected benefits of improved functional and electrophysiological outcomes with dynamic hypothermia titration, and 3) expected discovery of the protective mechanism behind therapeutic hypothermia and consequent glucose utilization and cortical electrophysiological function. The innovation in this project lies in 1) comprehensive and novel quantitative algorithm to systemically monitor and predict arousal after CA, 2) for the first time, guiding hypothermia delivery by the qEEG markers of brain's response to temperature, and 3) unique dual monitoring approach (PET and EEG) after CA to uncover hypothermia's protective mechanism. The approach to assess the improvement using glucose metabolic and electrophysiological recovery (EEG) patterns will be highly important to understand the mechanisms and develop a rational approach to hypothermia treatment. Our experimental model and the proposed technical approaches readily lend themselves to clinical translation: for example qEEG markers could easily be incorporated in a clinical bedside monitor. Like ubiquitous external defibrillator revolutionized heart protection, our novel monitoring and titration of hypothermia we hope will enter clinical practice.

描述（由申请人提供）： 美国每年发生超过 400,000 例心脏性猝死。在心脏骤停（CA）的幸存者中，脑损伤是功能恢复的最大障碍。诱导低温是目前唯一能够改善 CA 幸存者的生存率和神经系统结果的治疗形式。然而，几十年来，低温治疗一直盲目地转向更快的降温，并且没有大脑对温度反应的客观指标。到目前为止，还没有监测方法来指导低温治疗并提高其效率。这种疗法取得更有益效果的一个主要障碍是最佳低温水平和持续时间尚不清楚。低温保护作用的详细机制在很大程度上也是未知的。目标 1：我们的首要目标是开发和评估 CA 后功能结果的新型、非侵入性定量脑电图 (qEEG) 标记。我们测试以下假设：a) 基于我们新颖的基于熵的算法的 qEEG 分析将捕捉到 CA 前基线的电生理恢复，b) 子带中的顺序恢复将具有高度差异化的熵水平，并相应地对不同阶段表现出更大的敏感性损伤后的恢复和低温治疗的效果。目标 2：我们将使用 qEEG 标记来获取大脑对 a) 深度（温度水平）和 b) 低温递送持续时间的反应反馈。我们将测试以下假设：qEEG 电生理监测将作为大脑恢复的生物标志物，从而为低温治疗提供客观指导。目标 3：我们最后一个广泛的目标是客观分析低温对 CA 后葡萄糖利用时空模式的影响（通过小动物正电子发射断层扫描 (PET) 成像和电生理恢复 (EEG)）。我们测试了这样的假设：低温会增加葡萄糖的再利用，并改变皮质下和皮质大脑区域的空间模式，这有助于相应的脑电图变化信号恢复，并提前恢复正常，从而改善 CA 后的功能结果。该项目的意义有三方面：1) 开发和系统评估 CA 后脑损伤的简单客观 qEEG 监测工具，2) 通过动态低温滴定改善功能和电生理结果的预期益处，以及 3) 预期发现治疗性低温背后的保护机制以及随后的葡萄糖利用和皮质电生理功能。该项目的创新之处在于 1) 全面且新颖的定量算法，用于系统监测和预测 CA 后的觉醒，2) 首次通过大脑对温度反应的 qEEG 标记来指导低温传递，以及 3) 独特的双重监测方法（PET 和 EEG）CA 后揭示低温的保护机制。使用葡萄糖代谢和电生理恢复（EEG）模式来评估改善情况的方法对于理解机制和制定合理的低温治疗方法非常重要。我们的实验模型和提出的技术方法很容易应用于临床转化：例如，qEEG 标记可以很容易地纳入临床床边监测仪中。就像无处不在的体外除颤器彻底改变了心脏保护一样，我们希望新型的低温监测和滴定技术能够进入临床实践。