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: 9035424
• 负责人: Xiaofeng Jia
• 金额: $ 38.38万
• 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 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9035424
• 关键词: Affect; Algorithms; Animals; Area; Arousal; Biological Markers; Blood Glucose; Brain; Brain Injuries; Brain region; Categories; Cerebrum; Clinical; Coma; Consumption; Development; Electroencephalography; Electrophysiology (science); Entropy; Evaluation; Evolution; Experimental Models; External Defibrillator; Feedback; Frequencies; Glucose; Goals; Heart; Heart Arrest; Histology; Image; Injury; Measures; Metabolic; Metabolism; Methodology; Methods; Monitor; Neurologic Deficit; Neurological outcome; Outcome; Patient Monitoring; Pattern; Phase; Play; Positron-Emission Tomography; Procedures; Recovery; Recovery of Function; Resuscitation; Role; Signal Transduction; Standardization; Survivors; Synapses; Temperature; Testing; Thalamic structure; Therapeutic; Therapeutic Effect; Time; Titrations; base; clinical practice; clinical translation; clinically relevant; functional outcomes; glucose metabolism; improved; induced hypothermia; innovation; natural hypothermia; neurological recovery; neuroprotection; novel; outcome prediction; prevent; prognostic; protective effect; public health relevance; response; response to injury; restoration; spatiotemporal; sudden cardiac death; survival outcome; tool; Affect; Algorithms; Animals; Area; Arousal; Biological Markers; Blood Glucose; Brain; Brain Injuries; Brain region; Categories; Cerebrum; Clinical; Coma; Consumption; Development; Electroencephalography; Electrophysiology (science); Entropy; Evaluation; Evolution; Experimental Models; External Defibrillator; Feedback; Frequencies; Glucose; Goals; Heart; Heart Arrest; Histology; Image; Injury; Measures; Metabolic; Metabolism; Methodology; Methods; Monitor; Neurologic Deficit; Neurological outcome; Outcome; Patient Monitoring; Pattern; Phase; Play; Positron-Emission Tomography; Procedures; Recovery; Recovery of Function; Resuscitation; Role; Signal Transduction; Standardization; Survivors; Synapses; Temperature; Testing; Thalamic structure; Therapeutic; Therapeutic Effect; Time; Titrations; base; clinical practice; clinical translation; clinically relevant; functional outcomes; glucose metabolism; improved; induced hypothermia; innovation; natural hypothermia; neurological recovery; neuroprotection; novel; outcome prediction; prevent; prognostic; protective effect; public health relevance; response; response to injury; restoration; spatiotemporal; sudden cardiac death; survival outcome; 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）： 每年在美国发生40万多次心脏死亡。在心脏骤停的幸存者中，脑损伤是功能恢复的最大障碍。诱发体温过低是目前唯一改善CA幸存者生存和神经系统效果的治疗形式。但是，几十年来，体温过低一直盲目地针对更快的冷却，并且没有客观的大脑对温度反应的指标。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。这种疗法更有益结果的主要障碍是，体温过低的最佳水平和持续时间尚不清楚。体温过低的保护作用所基于的细节机制也在很大程度上未知。目标1：我们的第一个目标是开发和评估新颖，无创，定量的脑电图（QEEG）在大约之后的功能结果标记。我们测试了以下假设：a）基于我们的新型基于熵的算法的QEEG分析将捕获电生理恢复到前CA基线，并且b）子带中的顺序恢复将具有高度分化的熵水平，并且相应地表现出对损伤后恢复和效果的不同阶段的敏感性更高，并具有更高的效果。 AIM 2：我们将使用QEEG标记来获得有关大脑对A）深度（温度水平）和B）递送持续时间的反应的反馈。我们将检验以下假设：QEEG进行的电生理监测将成为大脑恢复的生物标志物，因此将为体温过低提供客观的指导。 AIM 3：我们的最后一个广泛目标是对体温过低对葡萄糖利用的时空模式的影响进行客观分析（通过小动物正电子发射断层扫描（PET）成像和电生理恢复（EEG））。我们测试了低温会增加葡萄糖的重新利用并改变皮层和皮质大脑区域的空间模式的假设，这有助于相应的脑电图改变信号恢复，并较早地归一化，以改善CA之后的功能性结果。该项目的重要性是三倍：1）CA之后的简单和客观QEEG监测脑损伤的工具的开发和系统评估，2）通过动态的低温滴定，改善功能和电生理结果的预期益处，以及3）预期的治疗机制背后使用治疗机制背后的保护性机制，以及葡萄糖性低热的效率和CORTICATIC PORIPTION和CORTICATIC ELECTOPLICTICALICICICICICIal Electoplysiolation yroplysiolation yroplysiolation yroplysicaliqualification yroplysiolation。该项目的创新在于1）全面和新颖的定量算法，以系统地监测和预测CA之后的唤醒，第2）首次指导大脑对温度反应的QEEG标记的低温标记，3）独特的双重监测方法（PET和EEG）在CA之后，以揭示了失常的保护机制。使用葡萄糖代谢和电生理恢复（EEG）模式评估改进的方法对于理解机制并开发出低温治疗的理性方法非常重要。我们的实验模型和提出的技术方法很容易将自己带入临床翻译：例如，可以轻松地将QEEG标记纳入临床床旁监视器中。像无处不在的外部除颤器一样彻底改变了心脏保护，我们希望对体温过低的新颖监测和滴定我们希望进入临床实践。