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独特特征，其在毛细血管水平上的特征在于没有窗孔的紧密细胞间连接，并将大脑与身体的其余部分隔离。在许多脑病理中，血脑屏障的破坏是疾病的特征;这种病理的例子是再灌注脑缺血性梗塞和脑肿瘤。我们建议开发磁共振成像（MRI）技术，评估脑血管床的渗透性的化合物。从小到大，这些是：Gd-DTPA，钆-17，白蛋白络合Gd，和超小颗粒的氧化铁（USPIO的）。这些化合物将用于再灌注脑缺血性梗死和脑肿瘤的治疗。我们已经开发了技术来测量血脑屏障（BBB）的渗透性MRI造影剂在再灌注脑缺血性梗死和脑肿瘤的大鼠模型。我们已经开发，完善，并在初步研究中，测量血脑屏障渗透性的水和磁共振造影剂的理论确认。我们建议进一步发展MRI技术和分析，确定再灌注脑缺血性梗死和脑肿瘤模型中MRI造影剂的传递常数和渗透性-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，以及脑血管系统的相对脑血容量（rCBV）。我们将在Fischer 344大鼠的9L肿瘤和Wistar大鼠的再灌注缺血性梗死中证明这些措施。

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.