High-Resolution Structural and Functional Assessments of Cerebral Microvasculature after Cerebral Ischemia by Magnetic Resonance Imaging
Date Issued
2015
Date
2015
Author(s)
Huang, Chien-Hsiang
Abstract
Vascular remodeling is an important mechanism to rescue the affected tissues after ischemia. Current therapies for stroke base on amplifying the angiogenesis. Understanding the structural and functional changes of the cerebral microvasculature may facilitate the development of the novel angiogenic therapies for stroke. The purpose of this dissertation is to use gas-challenged blood oxygen level-dependent (BOLD) MRI to assess the vascular structure and function. There are two parts in this dissertation. The first part is to develop a new method that simultaneously visualizes the cerebral microvasculature and obtains relative cerebral blood volume (rCBV). The second part is to apply the previously developed approach to investigate the vascular reactivity (VR) and functionality (VF) at the proangiogenic stage after ischemia. In the first part, the new method of 3D gas-challenged ΔR2*-based microscopic MRA (3D gas ΔR2*-mMRA) utilizes gas-challenged BOLD contrast to assess rCBV and directly visualize the morphology of cerebral microvasculature in rat brains. The advantages of using 3D gas ΔR2*-mMRA to observe the microvasculature include the ability to distinguish air–tissue interfaces, a high vessel-to-tissue contrast, and not being affected by damage to the blood–brain barrier. A rat model of transient focal cerebral ischemia was used to demonstrate the ability of 3D gas ΔR2*-mMRA to provide information about poststroke revascularization at 3 days after reperfusion. However, this technique has some limitations that cannot be overcome and hence should be considered when it is applied, such as predominantly revealing venous vessels and magnifying vessel sizes due to the susceptibility effects. In the second part, using the rat stroke model, the hypercapnic BOLD response was used to evaluate VR, while the hyperoxic BOLD and tissue oxygen level-dependent (TOLD) responses were used to evaluate the VF at 1, 3, and 7 days after ischemia. VR is defined as the ability of the vasculature to dilate in response to an elevated partial pressure of carbon dioxide level in this dissertation. VF is defined as the ability of the vasculature to increase oxygen saturation in response to an elevated partial pressure of oxygen level. Vessel-like venous signals appeared on R2* maps on days 3 and 7, but not on day 1. The large hypercapnic BOLD responses on days 3 and 7 indicated that these areas have high VR. The temporal correlation between VR and the immunoreactivity to desmin and VEGF further indicates that the integrity of VR is associated with the pericyte coverage as regulated by the VEGF level. VF remained low on days 1, 3, and 7, as reflected by the small hyperoxic BOLD and large hyperoxic TOLD responses, indicating the low oxygen consumption of the ischemic tissues. The method development of 3D gas ΔR2*-mMRA and the investigations of VR and VF after ischemia in this dissertation may offer the opportunity to thoroughly understand both the structural and functional characteristics of microvascular alterations after ischemia.
Subjects
cerebral ischemia
vascular remodeling
vascular structure
vascular function
BOLD MRI
Type
thesis
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