Project Summary / Abstract: The microvascular arterial system plays a key role in delivering oxygen and glucose to fulfill the high metabolic demand of the brain. Recently, microvascular abnormalities have been increasingly identified as the source or basis of many neurologic disorders including age-related dementia. Today, the mechanisms of both structural and functional changes due to aging are still largely unclear, and there is an urgent need for in vivo characterization as to how small vessel ages over the life course in both male and female adults. Although MRI is able to image the structural aspects of the brain with a resolution of 1mm today, it has not yet been used to study microvascular details in humans in vivo at the in-plane resolution of 100μm or less. We have developed a means by which to modify the susceptibility of the arteries using an ultra-small-superparamagnetic-iron-oxide (USPIO) to make it possible to image both small arteries and veins with susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) to see micro vessels less than 100μm. Our interest in this proposal is to bring together experts in a variety of medical and scientific areas such as MR physics, image processing and reconstruction to develop a new technique which we refer to ultra-high resolution USPIO-enhanced MR arteriogram and venogram (USPIO+-MRAV). We will take advantage of the blooming effect from the USPIO and the shift in susceptibility to create new means to image both arterioles and venules at the 50μm to 100μm level on both 3T and 7T MRI scanners. We expect to have a clinically viable method to create a “microvascular print” of the brain's angio-architecture based on 3D vascular tracking to assess micro-vessel topology and distribution that are not available on conventional imaging. We will develop quantitative measures of vascular density and capillary density to evaluate age-related changes in a cohort of healthy volunteers aged from 18 to 85 years. If successful, this innovative technology is expected to provide fundamental insights on how age-related microvascular alteration is detected and interpreted with in vivo brain imaging.