This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Affecting 10% of the world's population, Alzheimer's disease (AD) is one of the most common forms of dementia in the elderly. Despite enormous investigative efforts, the pathological basis for AD remains unclear. Recently, it was hypothesized that AD may be an angiogenesis-dependent disorder and anti-angiogenic drugs might be able to prevent and treat this disease. Researchers suggest that imaging vascular alterations, such as angiogenesis, could serve as a biomarker for AD disease onset and progression. Here we present the first MRI demonstration of AD associated angiogenesis by using a technique based on endogenous blood oxygenation level dependent (BOLD) effect. Relative to normoxia, hypoxia inhalation (8% O2) significantly reduces MR signal from cerebral vasculature, creating much higher BOLD effect than hyperoxia (100% O2). While signal from AD plaques and normal brain tissue is less sensitive to oxygenation changes, resulting in a clear cerebral vasculature image (CBV map), the relationship between AD plaque and vasculature network can be characterized. We demonstrate that the endogenous BOLD effect induced by hypoxia enables the visualization of angiogenesis and vasculature alterations associated with AD pathology in mice. It avoids confounding factor due to vessels permeability common in Dynamic Contrast Enhanced MRI (DCE-MRI) methods and produces much higher sensitivity than the endogenous contrast from Arterial Spin Labeling (ASL) MRI. With further development, MRI of angiogenesis and vasculature alternations could serve as a sensitive tool for investigation of AD pathology, early diagnosis and testing therapeutic efficacy of novel drugs.
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