White matter (WM) comprises about half of the brain (the other being the gray matter, GM), and is composed of bundles of myelinated nerve cell processes that connect various brain regions to each other. WM dysfunction is implicated in a number of neurological diseases such as Alzheimer's Disease, multiple sclerosis, and brain injury. At present, diagnostic and mechanistic studies of WM diseases primarily rely on structural imaging techniques such as T2-weighted image and Diffusion Tensor Imaging (DTI). Physiologic changes usually takes place before structure is altered, thus imaging of related parameters such as vascular physiology may provide an early marker for disease diagnosis and progression. While vascular physiology in the GM has been studied for more than a century, little is known about vascular physiology in the WM and researchers simply assume that WM vascular physiology follows the same rules as those for the GM except that everything is smaller in amplitude (because WM contains 70-75% less vasculature compared to GM). The goal of the present study is to challenge these traditional views by showing that blood supply and its regulation in the WM follow principles distinctive from that in the GM. We will further show that age-related changes in WM blood supply are also characteristically different from those in the GM. The proposed work was motivated by a series of surprising findings made by our group and others. First, despite recent availability of ultrahigh field (e.g. 7T) MRI, fMRI responses in the WM are rarely reported. Note that this cannot be explained by a lack of sensitivity, as WM fMRI signal (if present) at 7T/9.4T should be at least as large as GM signal at 1.5T. Second, we have initial evidence that baseline CBF in certain WM regions (e.g. frontal and parietal WM) actually increases with aging, in contrary to the situation in the GM where CBF decreases with aging. Finally, it is well known that GM CBF can be modulated by vasodilators such as CO2 inhalation. Our preliminary studies suggested that this principle is not applicable for WM and, if anything, higher CO2 corresponds to a lower CBF in the WM. These paradoxical findings led us to propose that vascular physiology in the WM is fundamentally different from that in the GM. This project has three Specific Aims.
Aim 1 : Determine spatial distribution of WM CBF at the level of individual fiber tracts and examine whether WM CBF has a relationship with other WM and GM biomarkers.
Aim 2 : Examine how WM CBF responds to vascular challenges and how the responses are different from those in the GM.
Aim 3 : Characterize age-related differences in WM vascular parameters. The present study serves as the first step to unravel the mechanism of blood supply in the WM. By demonstrating that WM vascular parameters can be determined reliably using state-of-the-art imaging methods and elucidating how blood supply is distributed and controlled in healthy WM, this study may open new avenues for future research of WM diseases.
Blood supply to one type of brain tissue called white matter is poorly understood and may be critical in several brain diseases such as Alzheimer's Disease; multiple sclerosis; and brain injury. The present study aims to improving our understanding of this phenomenon by measuring a comprehensive set of vascular parameters using non-invasive MR imaging technologies. This study will also investigate how blood supply in older individuals may be different from that in young participants.
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