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.
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