Recent evidence supports the notion that microvascular abnormalities and dementia are closely related; specifically, chronic and uncontrolled hypertension (HTN) is an important cause of cognitive decline in older people. We have developed a means by which to modify the susceptibility of the arteries using an ultra-small- superparamagnetic-iron-oxide (USPIO) to image the arteries with susceptibility weighted imaging (SWI) and mapping (SWIM) at the 50?m-100?m level. With this modification an entirely new research avenue of imaging small vessel diseases becomes possible. The goal of this proposal is to provide the Radiology and scientific community with the next generation of microvascular imaging, which we refer to as MICRO for ?Microvascular In-vivo Contrast Revealed Origins?. MICRO will make it possible to study the brain?s microvascular network including morphological and architectural changes at the arteriole and venule levels. In order to achieve our goals using MICRO MRAV (MR arterio-venous angiogram), we will use the susceptibility properties and blooming artifact from the USPIO as well as sub-voxel diffraction using a super-resolution strategy to image both arterioles and venules at the 50?m-100?m level.
Aim 1. To develop MICRO MRAV based on the combination of each of the above four concepts with simulations and human experiments to achieve the maximal SNR with minimal dose of Ferumoxytol at each field strength.
Aim 2. To create a 3D cerebral microvascular architecture print (cMAP) that allows for the quantification of both vascular density (VD) and capillary density (CD) for clinical use based on ultra-high resolution MICRO.
Aim 3. To apply MICRO MRAV to map the vasculature in normal rats for modeling purposes and validation and to quantify the microvascular abnormalities in an animal model for hypertension and stroke.
Aim 4. To apply MICRO MRAV in patients with mild cognitive impairment (MCI) who have chronic HTN (HTN/MCI) and determine its role in correlating with clinical symptoms and distinguishing changes from cognitively normal HTN patients and age- and gender- matched healthy controls. If successful, this innovative technology is expected to change how clinical diagnosis is made and how microvascular pathophysiology is detected and interpreted in patients with early dementia.
In this proposal, we will bring together experts in a variety of medical and scientific areas such as MR physics, vascular pathophysiology, image processing and reconstruction to plan the next generation of microvascular imaging, which we refer to as MICRO or, ?Microvascular In-vivo Contrast Revealed Origins? to study microvascular details in animals and in humans with hypertension and mild cognitive impairment using in vivo MRI with an in-plane resolution on the order of 50?m to 100?m.
