Human Brain Vascular Phenotyping with High-Field MRI:Water Permeability Mapping

使用高场 MRI 进行人脑血管表型分析：水渗透性绘图

• 批准号: 7245497
• 负责人: WILLIAM D ROONEY
• 金额: $ 31.17万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-21 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7245497
• 关键词: Accounting; Area; Blood; Blood - brain barrier anatomy; Blood Vessels; Blood Volume; Blood capillaries; Brain; Brain Mapping; Carrier Proteins; Cerebrum; Data; Dependence; Detection; Development; Diffuse; Disease; Edema; Equilibrium; Extravasation; Gadolinium; Goals; Health; Homeostasis; Human; Image; Imaging Techniques; Inflammatory; Invasive; Investigation; Kinetics; Knowledge; Laboratories; Lead; Lesion; Magnetic Resonance Imaging; Maps; Measurement; Measures; Metabolic; Methods; Modeling; Molecular; Molecular Weight; Multiple Sclerosis; Multiple Sclerosis Lesions; Pathology; Permeability; Phenotype; Physiological; Physiology; Play; Process; Property; Protons; Public Health; Rate; Reagent; Recording of previous events; Regulation; Relaxation; Research; Research Personnel; Resolution; Role; Speed; Standards of Weights and Measures; Surface; System; Techniques; Testing; Therapeutic Intervention; Time; Tissues; Treatment Efficacy; Water; Woman; Work; angiogenesis; base; brain tissue; capillary; hormone regulation; improved; in vivo; insight; instrument; interstitial; magnetic field; men; molecular dynamics; nervous system disorder; novel; pharmacokinetic model; programs; response; sex; spatiotemporal

DESCRIPTION (provided by applicant): Project Summary: NMR has contributed a long and rich history of molecular dynamics and equilibrium exchange measurements. Arguably, this is one of its greatest strengths. The combination of these aspects with in vivo imaging capabilities is potentially extremely powerful, and has already provided important physiological insights. The long-term objective of this project is to improve MRI methods to map equilibrium water molecular exchange across the blood-brain-barrier (BBB). This goal will be accomplished using conventional FDA-approved, low-molecular weight gadolinium contrast reagents (CRs) in human brain at 7 Tesla (T), and applying the comprehensive shutter-speed pharmacokinetic models developed in our laboratory that properly account for water exchanges between multiple tissue compartments as well as CR extravasation. This project takes advantage of the concurrent increase in the tissue water proton longitudinal relaxation time constant, and its dispersion, with magnetic field strength; a topic extensively studied by the PI and investigators. Taken together with the well-recognized S/N increases associated with increasing magnetic field, thus cause the CR detection limit to be greatly improved, which is crucial to this project. The use of a 7 T MRI instrument is expected to markedly improve the precision and accuracy of human brain parametric maps. In the normal brain, the trans-BBB permeability coefficients for water and CR (really, permeability surface area products) differ by four orders of magnitude (or more), and each is related to a different aspect of small vessel physiology. The overall goals of the proposed work are: a) to improve our MRI methods to obtain accurate and reliable human brain BBB water permeability maps, and b) to investigate sex dependences of BBB water permeability, and c) to investigate the association between BBB water permeability and multiple sclerosis (MS) disease expression. Relevance to Public Health: The control and regulation of brain water content is important in the progression of many diseases. The investigations proposed here will explore the novel, non-invasive MRI measurement of water exchange between blood and brain. This research will lead to a more complete understanding of water homeostasis in normal brain and how it is perturbed in MS. Emerging MS therapies have targeted BBB water transport proteins, and methods developed in this project will lead to non-invasive assessment of the efficacies of these interventions.

描述（由申请人提供）：项目摘要：NMR贡献了分子动力学和平衡交换测量的悠久历史。可以说，这是其最大的优势之一。这些方面与体内成像能力的结合可能非常强大，并且已经提供了重要的生理见解。该项目的长期目标是改善MRI方法，以绘制跨血脑屏障（BBB）绘制平衡水分子交换。该目标将使用传统的FDA批准，低分子量的低分子量gadolinium对比试剂（CRS）在7 tesla（t）的人脑中，并应用我们实验室中开发的全面的快门速度速度药物模型在多个组织室之间以及Cr渗出之间。该项目利用了组织水质子纵向松弛时间常数的同时增加，并具有磁场强度的分散体。 PI和研究人员对这个主题进行了广泛的研究。结合与磁场增加相关的良好认可的S/N的增加，从而导致CR检测极限得到极大的改善，这对该项目至关重要。 7 T MRI仪器的使用有望明显提高人脑参数图的精度和准确性。在正常的大脑中，水和Cr的反式BBB渗透率系数（实际上，渗透率表面积）差异四个数量级（或更多），并且每种均与小血管生理学的不同方面有关。拟议工作的总体目标是：a）改进我们的MRI方法，以获取准确可靠的人脑BBB水的渗透率图，b）研究BBB水渗透性的性别依赖性，c）研究BBB水之间的关联渗透性和多发性硬化症（MS）疾病表达。与公共卫生有关：脑含水含量的控制和调节在许多疾病的发展中很重要。这里提出的研究将探讨血液与大脑之间水交换的新颖，无创的MRI测量。这项研究将使对正常大脑中的水稳态以及MS的干扰有更全面的了解。新兴的MS疗法针对BBB水转运蛋白，该项目中开发的方法将导致对这些干预措施的效果的无创评估。