In vivo MRI Measures of Brain Metabolism in Traumatic Brain Injury

创伤性脑损伤中脑代谢的体内 MRI 测量

• 批准号: 10444479
• 负责人: Tsang-Wei Tu
• 金额: $ 39.39万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444479
• 关键词: Acute; Affect; Alzheimer' s Disease; Animals; Area; Autoradiography; Behavioral; Bioenergetics; Biological Assay; Blood - brain barrier anatomy; Blood Glucose; Brain; Brain Injuries; Brain region; Cause of Death; Cerebrovascular Circulation; Cerebrum; Chemicals; Chronic; Clinical; Clinical Trials; Data; Development; Diagnosis; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Energy Metabolism; Epilepsy; Event; Foundations; Functional disorder; Glucose; Goals; Head; Human; Hypoxia; Image; Image Enhancement; Imaging Device; Immunohistochemistry; Impairment; Injury; Intervention; Lithium; Magnetic Resonance Imaging; Measures; Mechanics; Mental Depression; Metabolic; Metabolic Diseases; Metabolism; Methodology; Microdialysis; Modality; Modeling; Molecular; Mood stabilizers; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neurological outcome; Outcome; Pathology; Patients; Perfusion; Pharmacotherapy; Phase; Positron-Emission Tomography; Process; Prognosis; Protons; Public Health; Publishing; Quality of life; Radioisotopes; Rattus; Resolution; Risk; Scheme; Sensitivity and Specificity; Severities; Signal Transduction; Source; Spectrum Analysis; TBI treatment; Techniques; Time; TimeLine; Tissues; Tracer; Translating; Traumatic Brain Injury; Treatment Efficacy; United States; United States Food and Drug Administration; Valproic Acid; analytical method; axon injury; base; blood flow measurement; brain metabolism; brain tissue; clinically relevant; contrast enhanced; design; disability; efficacy evaluation; glucose metabolism; glucose monitor; improved; in vivo; neurotransmission; neurotransmitter release; neurovascular; neurovascular coupling; non-invasive imaging; non-invasive monitor; novel; personalized care; prognostic indicator; public health relevance; repaired; therapy development; tissue injury; tool; treatment effect; treatment strategy

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.

项目摘要 创伤性脑损伤（TBI）是美国主要的公共卫生问题。TBI可能导致 长期神经系统并发症，包括神经变性、行为功能障碍、抑郁症和 严重影响患者生活质量的癫痫。大脑葡萄糖利用率已被发现下降60% 是TBI长期预后的预后指标之一。两 动物和人体研究已经确定，脑血流之间的神经血管解偶联 (CBF)脑组织能量需求是TBI脑代谢危象的关键因素。的 神经血管解偶联导致能量不匹配，破坏正常神经胶质细胞功能， 修复过程。尽管对潜在的治疗方法进行了大量的临床试验，但美国食品和药物管理局（FDA） 管理局批准的用于治疗TBI的药物疗法。临床试验失败的原因之一是 不能准确评估脑葡萄糖代谢的区域特异性扰动， 确定治疗是否可以恢复TBI大脑中的神经血管耦合。快速血糖测量 技术，包括微透析、持续血糖监测、光谱学或正电子发射 使用示踪放射性同位素的断层摄影术（PET）提供的分辨率不足以确定区域特异性 葡萄糖在大脑中的利用。在这项提议中，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，提供测量所需的高分辨率 TBI的区域特异性代谢葡萄糖检测CEST MRI（glucoCEST）通过以下方式测量脑葡萄糖： 不使用放射性同位素检测葡萄糖的可交换质子信号， 成像分辨率比PET扫描高100倍。我们的初步和公布的数据 表明glucoCEST可能是可行的，以检测大鼠弥漫性TBI的延迟代谢低下。我们 建议结合联合收割机高分辨率glucoCEST和动态对比增强（DCE）灌注MRI， 伴随CBF测量以识别TBI后随时间推移的神经血管耦合状态。我们的目标 设计用于（1）识别TBI脑中体内glucoCEST的对比机制，以增强TBI脑中的 采用先进的采集方案和分析模型，检测glucoCEST的灵敏度和特异性（2） 表征脑葡萄糖代谢的扰动和TBI脑中的灌注缺陷，以及（3） 证明双模态CEST-DCE MRI在无创监测 临床推荐的TBI干预治疗效果。总的来说，这些研究将提供一个强有力的 技术和科学基础，以推动该领域在利用先进的MRI进行个性化 在临床竞技场中进行护理，并确定脑损伤患者的最佳治疗策略。