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

描述(由申请人提供)：项目摘要：核磁共振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，这是它最大的优势之一。这些方面与体内成像能力的结合潜在地非常强大，并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，以绘制跨越血脑屏障(BBB)的平衡水分子交换图。这一目标将在7特斯拉(T)的人脑中使用FDA批准的常规低分子Gd造影剂(CRS)实现，并应用我们实验室开发的全面的快门速度药代动力学模型，该模型正确地考虑了多个组织间的水交换以及CR的外渗。这个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的优势；这是PI和研究人员广泛研究的一个主题。再加上公认的S/氮随磁场增加而增加，从而导致CR的检测限大大提高，这对这个项目至关重要。7T磁共振成像仪器的使用有望显著提高人脑参数图的精确度和准确度。在正常大脑中，水和CR(实际上是渗透表面积乘积)的跨血脑屏障通透性系数相差四个数量级(或更多)，每一个都与小血管生理的不同方面有关。这项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水渗透图，b)调查BBB水渗透的性别相关性，以及c)调查BBB水渗透与多发性硬化症(MS)疾病表现之间的关系。与公共健康相关：控制和调节大脑水分含量在许多疾病的发展过程中非常重要。本文提出的研究将探索新的、非侵入性的MRI测量血液和大脑之间的水交换。这项研究将导致更全面地了解正常大脑中的水稳态以及它是如何在多发性硬化症中受到干扰的，新兴的多发性硬化症治疗方法以血脑屏障水运输蛋白为靶标，该项目开发的方法将导致对这些干预措施的有效性的非侵入性评估。

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.