MRI Measure of Blood Brain Barrier Permeability

描述(由申请人提供)： 血脑屏障是脑血管系统的一个独特特征，在毛细血管水平上的特征是紧密的细胞间连接，没有窗孔，并将大脑与身体的其他部分隔离开来。在许多脑部病理中，血脑屏障的破坏是这种疾病的特征；这类病理的例子有再灌注性脑缺血和脑肿瘤。我们建议开发磁共振成像(MRI)技术来评估脑血管床对各种化合物的通透性。从小到大是：Gd-DTPA、Gadmer-17、白蛋白络合物Gd和超小颗粒氧化铁(USPIO)。这些化合物将用于再灌注性脑梗塞和脑肿瘤。在大鼠脑缺血再灌注和脑肿瘤模型中，我们开发了测量血脑屏障(BBB)对MRI造影剂渗透性的技术。我们已经开发、完善并在初步研究中证实了测量血脑屏障对水和磁共振造影剂渗透性的理论。我们建议进一步发展MRI技术和分析，以确定MRI对比剂在大鼠脑缺血再灌注和脑肿瘤模型中的转移常数和渗透表面积乘积(PS乘积)。此外，我们将研究MRI方法来估计脑组织的细胞外、血管外体积分数，以及脑血管的相对脑血容量(RCBV)。我们将在Fischer 344大鼠的9L肿瘤和Wistar大鼠的再灌流脑梗塞中展示这些措施。

DESCRIPTION (provided by applicant): The blood-brain barrier is a unique feature of cerebral vasculature, characterized at the capillary level by tight intercellular junctions devoid of fenestrae, and isolating the brain from the rest of the body. In many cerebral pathologies, a breakdown of the blood-brain barrier is a characteristic of the disease; examples of such pathologies are reperfused cerebral ischemic infarction and cerebral tumor. We propose to develop magnetic resonance imaging (MRI) techniques that assess the permeability of the cerebral vascular bed for a wide range of compounds. From small to large these are: Gd-DTPA, gadomer-17, albumin-complexed Gd, and ultrasmall particles of iron oxide (USPIO's). These compounds will be used in reperfused cerebral ischemic infarction and cerebral tumor. We have developed techniques to measure blood-brain barrier (BBB) permeability to MRI contrast agents in rat models of reperfused cerebral ischemic infarction and cerebral tumor. We have developed, refined, and confirmed in preliminary studies, theories for measuring BBB permeability to water and to magnetic resonance contrast agents. We propose to further develop MRI techniques and analyses that determine the transfer constant and permeability-surface area product (PS product) of MRI contrast agents in rat models of reperfused cerebral ischemic infarction and cerebral tumor. Additionally, we will investigate MRI methods to estimate the extracellular, extravascular volume fraction of the cerebral tissue, and the relative cerebral blood volume (rCBV) of the cerebral vasculature. We will demonstrate these measures in 9L tumors in Fischer 344 rats, and in reperfused ischemic infarction in Wistar rats.