Predicting Brain Recovery after Acute Hemorrhage and Resuscitation

描述(申请人提供)：本研究项目的总体目标是开发一种非侵入性磁共振/光学成像测试，以使用大鼠模型评估和预测急性出血后的缺血性脑损伤和恢复。遭受急性失血(如创伤、手术、胃肠道出血)的患者通常在输血可用和被认为有必要之前，首先用无血性盐溶液复苏。红细胞质量的丧失和血液稀释会减少组织中的氧气输送。大脑对氧气输送特别敏感；即使是相对较短的组织缺氧期也可能导致永久性损伤或中风。目前，还没有临床上可用的方法来评估足够的氧气输送到大脑和预测中风；复苏和输血完全由随意的临床指南指导。评估这类患者是否有足够的氧气供应将导致更有效的治疗。此外，目前还没有出血和复苏的动物模型，既不能评估预测中风的成像方法，也不能用无血性液体、血液或氧气载体进行适当的复苏。这一建议的总体假设是，我们可以使用磁共振(MR)和漫反射光学断层扫描(DOT)提供的信息来预测急性出血和复苏24小时后脑组织的状态。具体目标是：目标1。)建立啮齿动物急性出血/复苏模型，包括在24小时内恢复和跟踪成像，从而产生缺血性脑损伤，同时优化输血方案以避免死亡。目标2。)在出血/复苏和恢复期间，测量MR松弛速率、波谱和整个大脑的弥散参数的变化，以及用DOT测量局部氧/脱氧/总血红蛋白的变化。这些急性测量将与出血后24小时中风的成像和组织学分析进行比较。目标3。)评估几种方法来表征出血/复苏期间的多参数测量，以及预测预后的后续时间点。我们将首先使用ISODATA聚类算法和GLM作为预测映射的方法。运用最优分析方法，对基本假设进行检验。这项研究的成功结果将证明，急性非侵入性成像可以用来确定急性失血引起的可逆或不可逆脑缺血变化的程度，以及使用无血性液体、血液或氧气载体进行复苏的影响和最佳时机。这些数据将有力地支持使用MR和/或DOT来监测、评估和临床管理出血患者，并将为未来的人类研究指明方向。该研究项目的总体目标是开发一种非侵入性磁共振/光学成像测试，以使用实验动物(大鼠)模型评估和预测急性失血后的脑损伤和恢复。这项研究的成功结果将证明，急性诊断成像可以用于识别和定义急性出血引起的可逆或不可逆脑缺血变化的程度，以及阐明血液或人工血液替代品复苏的影响和最佳时机。这些数据将有力地支持这项技术的应用，以评估和管理出血患者，并为未来的人体研究指明方向。

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.