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: 7429699
• 负责人: WILLIAM D ROONEY
• 金额: $ 30.56万
• 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/7429699
• 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 在分子动力学和平衡交换测量方面贡献了悠久而丰富的历史。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学见解。该项目的长期目标是改进 MRI 方法，以绘制血脑屏障 (BBB) 上的平衡水分子交换图。这一目标将通过在 7 特斯拉 (T) 的人脑中使用经 FDA 批准的传统低分子量钆造影剂 (CR) 并应用我们实验室开发的综合快门速度药代动力学模型来实现，该模型可以正确解释多个组织隔室之间的水交换以及 CR 外渗。该项目利用了组织水质子纵向弛豫时间常数及其色散随磁场强度的同时增加； PI 和研究人员广泛研究的一个主题。加上众所周知的信噪比随磁场增加而增加，从而导致 CR 检测限大大提高，这对于该项目至关重要。 7T MRI仪器的使用有望显着提高人脑参数图的精度和准确度。在正常大脑中，水和 CR（实际上是渗透性表面积乘积）的跨 BBB 渗透系数相差四个数量级（或更多），并且每个系数都与小血管生理学的不同方面相关。拟议工作的总体目标是：a）改进我们的 MRI 方法，以获得准确可靠的人脑 BBB 水渗透性图，b）研究 BBB 水渗透性的性别依赖性，c）研究 BBB 水渗透性与多发性硬化症（MS）疾病表达之间的关联。与公共健康的相关性：脑含水量的控制和调节对于许多疾病的进展非常重要。这里提出的研究将探索血液和大脑之间水交换的新型、非侵入性 MRI 测量。这项研究将有助于更全面地了解正常大脑中的水稳态以及在多发性硬化症中水稳态如何受到干扰。新兴的 MS 疗法以 BBB 水转运蛋白为目标，该项目开发的方法将对这些干预措施的功效进行非侵入性评估。