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: 10614054
• 负责人: Tsang-Wei Tu
• 金额: $ 39.13万
• 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/10614054
• 关键词: Acceleration; 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; Failure; Foundations; Functional disorder; Glucose; Goals; Head; Human; Hypoxia; Image; Image Enhancement; Imaging Device; Immunohistochemistry; Impairment; Injury; Intervention; Lithium; Magnetic Resonance Imaging; Maps; Measures; Mechanics; Mental Depression; Metabolic; Metabolic Diseases; Metabolism; Methodology; Microdialysis; Modality; Modeling; Molecular; Mood stabilizers; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neurological outcome; Non-Invasive Detection; Outcome; Pathology; Patients; Perfusion; Pharmacotherapy; Phase; Positron-Emission Tomography; Process; Prognosis; Protons; Public Health; Publishing; Quality of life; Radioisotopes; Rattus; Recommendation; Resolution; Risk; Scheme; Sensitivity and Specificity; Severities; Signal Transduction; Source; Spectrum Analysis; TBI Patients; TBI treatment; Techniques; Time; Tissues; Tracer; Translating; Traumatic Brain Injury; Treatment Efficacy; United States; United States Food and Drug Administration; Valproic Acid; analytical method; axon injury; 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; timeline; 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）代表了美国的主要公共卫生问题。 TBI可以导致 长期神经系统并发症，包括神经变性，行为功能障碍，抑郁和 严重影响患者生活质量的癫痫。发现脑葡萄糖的利用率已减少60％ 慢性TBI的患者是TBI长期预后的预后指标之一。两个都 动物和人类研究已经确定脑血流之间的神经血管解偶联 （CBF）和脑组织能量需求是TBI大脑中大脑代谢危机的关键因素。这 神经血管解偶联导致能量不匹配，会破坏正常的神经功能和逮捕 维修过程。尽管对潜在疗法进行了许多临床试验，但没有美国食品和药物 管理批准用于治疗TBI的药物治疗。临床试验失败的原因之一是 无法准确评估脑葡萄糖代谢和 确定治疗是否可以恢复TBI大脑中的神经血管耦合。存在的葡萄糖测量 技术，包括微透析，持续血糖监测，光谱或正电子发射 使用示踪剂放射性同位素的断层扫描（PET）提供的分辨率不足来确定特定区域 大脑中的葡萄糖利用。在此提案中，我们确定评估新型基于MRI的实用性 化学交换饱和转移（CEST）成像，以提供所需的高分辨率来测量 TBI的区域特异性代谢。葡萄糖检测CEST MRI（GELCOCEST）通过 检测葡萄糖的可交换质子信号，而无需使用放射性同位素并产生葡萄糖 分辨率的映射>比PET扫描高100倍。我们的初步和发布的数据有 证明糖蛋白可能是可行的，可以检测大鼠弥漫性TBI的延迟缺乏代谢。我们 提议将高分辨率葡萄糖蛋白和动态对比度增强（DCE）灌注MRI结合起来 随着时间的推移，TBI之后，CBF测量值鉴定了神经血管耦合状态。我们的目标 旨在（1）确定TBI大脑中体内葡萄糖蛋白的对比机制以增强 通过先进的采集方案和分析模型的葡萄糖的敏感性和特异性，（2） 表征脑葡萄糖代谢和TBI大脑灌注缺陷的扰动，（3） 证明双重模式CEST-DCE MRI的潜在应用无创监测 TBI临床推荐干预的治疗效果。总体而言，这些研究将提供强大的 技术和科学基础，以实现个性化的高级MRI利用来推动该领域的前进 在临床领域进行护理，并确定针对脑损伤患者的最佳治疗策略。