In vivo MRI Measures of Brain Metabolism in Traumatic Brain Injury

项目总结 创伤性脑损伤(TBI)在美国是一个主要的公共卫生问题。TBI可能会导致 长期的神经并发症，包括神经退行性变、行为障碍、抑郁和 严重影响患者生活质量的癫痫。有60%的人大脑葡萄糖利用率下降 是慢性脑损伤患者的主要预后指标之一，是判断脑外伤患者长期预后的指标之一。两者都有 动物和人类的研究已经证实，脑血流之间的神经血管解偶联 脑血流量和脑组织能量需求是导致颅脑损伤后脑代谢危机的关键因素。这个 神经血管解偶联导致能量不匹配，从而扰乱正常的神经胶质功能和停滞 修复过程。尽管有许多关于潜在疗法的临床试验，但美国没有食品和药物 政府批准了治疗脑外伤的药物疗法。临床试验失败的原因之一是 不能准确评估大脑葡萄糖代谢的区域特异性扰动和 确定一种治疗方法是否能恢复脑外伤脑内的神经血管偶联。现存血糖测量 技术，包括微透析、持续血糖监测、光谱分析或正电子发射 断层摄影术(PET)使用示踪放射性同位素，提供的分辨率不足以确定区域特异性 大脑中葡萄糖的利用。在这项建议中，我们决定评估一种新的基于MRI的 化学交换饱和转移(CEST)成像，为测量提供所需的高分辨率 脑损伤的区域特异性代谢。葡萄糖检测CEST磁共振成像(GloCEST)通过以下方式测量大脑葡萄糖 不使用放射性同位素检测葡萄糖的可交换质子信号并产生葡萄糖 以高于正电子发射断层扫描100倍的分辨率绘制地图。我们的初步数据和公布的数据 提示用葡糖CEST检测弥漫性脑损伤大鼠迟发性低代谢是可行的。我们 建议联合应用高分辨率葡聚糖凝胶成像和动态增强(DCE)磁共振灌注成像 同时进行CBF测量，以确定脑外伤后随时间推移的神经血管耦合状态。我们的目标 旨在(1)确定脑损伤后体内葡糖CEST的对比剂机制，以增强脑组织 采用先进的采集方案和分析模型的葡糖CEST的敏感性和特异性，(2) 表征脑葡萄糖代谢的扰动和脑损伤后的脑血流灌注缺陷，以及(3) 展示了双模式CEST-DCE MRI在无创性监测脑血管病变中的潜在应用 临床推荐的脑外伤介入治疗效果分析。总体而言，这些研究将提供强有力的 利用先进的磁共振技术实现个性化，为推动这一领域的发展奠定了技术和科学基础 在临床领域进行关怀，确定脑损伤患者的最佳治疗策略。

PROJECT SUMMARY Traumatic brain injury (TBI) represents a major public health concern in the United States. TBI can result in long-term neurological complications, including neurodegeneration, behavioral dysfunction, depression and epilepsy that seriously affect patient quality-of-life. Brain glucose utilization has been found decreased in 60% of patients with chronic TBI and is one of the prognostic indicators for the long-term outcome of TBI. Both animal and human studies have identified that the neurovascular uncoupling between cerebral blood flow (CBF) and brain tissue energy demands is a key factor for cerebral metabolic crisis in the TBI brain. The neurovascular uncoupling results in energy mismatch that disrupts normal neuroglial function and arrests repairing process. Despite numerous clinical trials on potential therapies, there is no U.S. Food and Drug Administration approved drug therapy for the treatment of TBI. One of the reason clinical trials failed is due to the inability that can accurately evaluate the region-specific perturbations of brain glucose metabolism and determine if a treatment can restore neurovascular coupling in the TBI brain. Existent glucose measuring techniques, including microdialysis, continuing blood glucose monitoring, spectroscopy, or positron emission tomography (PET) which uses tracer radioisotopes, provide insufficient resolution to determine region-specific glucose utilization in the brain. In this proposal, we determine to assess the utility of a novel MRI-based Chemical Exchange Saturation Transfer (CEST) imaging, to provide the needed high-resolution for measuring region-specific metabolism for TBI. The glucose detecting CEST MRI (glucoCEST) measures brain glucose by detecting the exchangeable proton signals of glucose without using radioisotopes and generates glucose mapping in a resolution >100 times higher than PET scans. Our preliminary and published data have demonstrated that glucoCEST may be feasible to detect the delayed hypometabolism of diffuse TBI in rats. We propose to combine high-resolution glucoCEST and the Dynamic Contrast Enhanced (DCE) perfusion MRI for concomitant CBF measurements to identify the neurovascular coupling state following TBI over time. Our aims are designed to (1) Identify the contrast mechanism of in vivo glucoCEST in the TBI brain to enhance the sensitivity and specificity of glucoCEST with advanced acquisition scheme and analytical models, (2) Characterize perturbations in brain glucose metabolism and perfusion deficits in the TBI brain, and (3) Demonstrate the potential application of the dual-modality CEST-DCE MRI to noninvasively monitor the treatment effects of a clinically-recommended intervention for TBI. Overall, these studies will provide a strong technical and scientific foundation to move the field forward in utilization of advanced MRI for personalized care in the clinical arena and determine the best treatment strategy for the brain injured patients.