Predicting Brain Recovery after Acute Hemorrhage and Resuscitation

预测急性出血和复苏后的大脑恢复

• 批准号: 7894723
• 负责人: JOHN J. A. MAROTA
• 金额: $ 22.07万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7894723
• 关键词: Acute; Adult; Algorithms; Anemia; Animal Experimentation; Animal Model; Animals; Blood; Blood Substitutes; Blood Transfusion; Blood flow; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Brain Ischemia; Carrying Capacities; Cerebral Ischemia-Hypoxia; Cerebral cortex; Cerebrovascular Circulation; Clinical; Data; Diagnosis; Diagnostic; Diagnostic Imaging; Diffusion; Diffusion Magnetic Resonance Imaging; Drops; Electrocardiogram; Erythrocytes; Evaluation; Functional Magnetic Resonance Imaging; Future; Gastrointestinal Surgical Procedures; Glutamates; Goals; Guidelines; Heart; Hemodilution; Hemoglobin; Hemorrhage; Hour; Human; Hypotension; Hypoxia; Image; Ischemia; Ischemic Brain Injury; Lead; Light; Liquid substance; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Metabolic; Methodology; Methods; Modeling; Monitor; N-acetylaspartate; Neurologic; Noise; Operative Surgical Procedures; Outcome; Outcome Study; Oxygen; Oxyhemoglobin; Patients; Perfusion; Physiological; Protocols documentation; Rattus; Recording of previous events; Recovery; Red Cell Mass result; Relaxation; Reperfusion Therapy; Research Project Grants; Resolution; Resuscitation; Risk; Rodent; Rodent Model; Signal Transduction; Sodium Chloride; Solutions; Spectrum Analysis; Stroke; Techniques; Technology; Testing; Thrombolytic Therapy; Time; Tissues; Transfusion; Trauma; Weight; absorption; acute stroke; brain tissue; clinical application; cranium; deoxyhemoglobin; diffuse optical tomography; effective therapy; follow-up; imaging modality; improved; light transmission; mortality; neonate; neuron loss; optical imaging; tool; transmission process

DESCRIPTION (provided by applicant): The overall goal of this research project is to develop a noninvasive Magnetic Resonance/Optical Imaging test to assess and predict ischemic brain damage and recovery after acute hemorrhage using a rat model. Patients who suffer acute blood loss (e.g. from trauma, surgery, gastrointestinal bleeding) are often initially resuscitated with asanguinous salt solutions before transfusion of blood is available and deemed necessary. Loss of red blood cell mass and hemodilution reduce oxygen delivery to tissues. The brain is particularly sensitive to oxygen delivery; even relatively short periods of tissue hypoxia can result in permanent damage or stroke. Presently, there is no clinically available method to assess adequate delivery of oxygen to the brain and predict stroke; resuscitation and transfusion is guided entirely by arbitrary clinical guidelines. Assessment of adequate oxygen delivery in such patients would lead to more effective treatment. Furthermore, there is no animal model of hemorrhage and resuscitation either to permit evaluation of imaging methods to predict stroke or appropriate resuscitation with asanguinous fluids, blood or oxygen carriers. The overall hypothesis of this proposal is that we can use information provided by magnetic resonance (MR) and diffuse optical tomography (DOT) to predict the status of brain tissue 24 hours after acute hemorrhage and resuscitation. The specific aims are: AIM 1.) Develop a rodent acute hemorrhage/resuscitation model to include recovery and follow-up imaging at 24 hrs that produces ischemic brain damage while optimizes transfusion protocol to avoid mortality. AIM 2.) Measure changes in MR relaxation rates, spectroscopy, and diffusion parameters throughout brain, as well as localized changes in oxy/deoxy/total hemoglobin with DOT during hemorrhage/resuscitation and recovery. These acute measurements will be compared to imaging and histological analysis of stroke 24 hours after hemorrhage. AIM 3.) Evaluate several approaches to characterize the multiparametric measurements during hemorrhage/resuscitation and follow-up time points to predict outcome. We will begin by using ISODATA clustering algorithm and GLM as approaches to predictive mapping. Using the optimum analysis method, we will test the primary hypothesis. A successful outcome from this study would demonstrate that acute noninvasive imaging could be used to define the extent of reversible or irreversible ischemic changes in brain from acute blood loss, as well as the impact and optimal timing of resuscitation with asanguinous fluids, blood or oxygen carriers. Such data would strongly support use of MR and/or DOT to monitor, assess and clinically manage hemorrhaging patients and would point the way for future studies in humans. The overall goal of this research project is to develop a noninvasive magnetic resonance/optical imaging test to assess and predict brain damage and recovery after acute blood loss using an experimental animal (rat) model. A successful outcome from this study would demonstrate that acute diagnostic imaging could be used to identify and define the extent of reversible or irreversible ischemic changes in brain caused by acute hemorrhage, as well as elucidate the impact and optimal timing of resuscitation with blood or artificial blood substitutes. These data would strongly support the application of this technology to assess and manage patients undergoing hemorrhage and would point the way for future studies in humans.

描述（由申请人提供）：该研究项目的总体目标是开发非侵入性磁共振/光学成像测试，以评估和预测使用大鼠模型急性出血后缺血性脑损伤和恢复。最初，在获得血液输血之前，通常会用微不足道的盐溶液复活并认为有必要。红细胞质量和血液稀释的损失减少了氧气递送到组织。大脑对氧递送特别敏感。即使是相对较短的组织缺氧，也可能导致永久性损害或中风。目前，尚无临床上可用的方法来评估氧气足够的大脑并预测中风。复苏和输血完全由任意临床准则指导。评估此类患者中足够的氧气递送将导致更有效的治疗。此外，没有动物模型的出血和复苏模型可以评估成像方法，以预测中风或使用无态流体，血液或氧气载体进行适当的复苏。该提案的总体假设是，我们可以使用磁共振（MR）和弥漫性光学层析成像（DOT）提供的信息来预测急性出血和复苏后24小时的脑组织状态。具体目的是：目标1.）开发一个啮齿动物急性出血/复苏模型，包括在24小时时恢复和随访成像，从而产生缺血性脑损伤，同时优化输血方案以避免死亡率。目标2.）衡量整个大脑中MR松弛率，光谱和扩散参数的变化，以及在出血/复苏和恢复过程中氧气/脱氧/总血红蛋白的局部变化。这些急性测量将与出血后24小时的成像和组织学分析进行比较。目标3.）评估几种方法，以表征出血/复苏期间多参数测量和随访时间点以预测结果。我们将首先使用ISODATA聚类算法和GLM作为预测映射的方法。使用最佳分析方法，我们将测试主要假设。这项研究的成功结果将表明，急性非侵入性成像可用于确定急性失血因急性失血而可逆或不可逆的缺血性变化的程度，以及用无为液体，血液或氧气载体使用急性流失的影响和最佳恢复时间。这样的数据将强烈支持MR和/或DOT的使用来监测，评估和临床管理出血患者，并将为未来在人类研究的过程中指出道路。该研究项目的总体目标是开发非侵入性磁共振/光学成像测试，以评估和预测使用实验动物（大鼠）模型急性失血后脑损伤和恢复。这项研究的成功结果将表明，急性诊断成像可用于识别和定义由急性出血引起的可逆性或不可逆性缺血性变化的程度，并阐明用血液或人工血液替代品恢复的影响和最佳时机。这些数据将强烈支持该技术在评估和管理发生出血的患者中的应用，并将指向未来在人类研究的道路。