Development of High Resolution Magnetic Resonance Perfusion Imaging and Angiography Technique: Structural and Functional Assessment of Cerebral Angiogenesis

• Main Authors: Chien-Yuan Lin, 林建源
• Other Authors: 陳志宏
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/07085460547759640615

博士 === 國立臺灣大學 === 電機工程學研究所 === 97 === The hemodynamic parameters such as vascular permeability, blood volume (BV), blood flow, and mean transient time obtained by dynamic magnetic resonance imaging with the utilization of contrast agent, have been widely used to study vascular remodeling in pathological tissue. However, these parameters obtained from the dynamic imaging technique require rapid imaging technique that severely compromises the spatial resolution. In addition, these parameters such as BV have been used to link the vessel density. It alone may not be a reliable indicator of microvessel density because the BV change reflects the combined effect on the average size and density of microvessels. Alternatively, steady-state contrast-enhanced magnetic resonance imaging (SSCE-MRI) with calculating the transverse relaxation rate shift in blood vessel due to the presence of the contrast agent has been proposed to study the microvasculature of pathological tissue. The gradient echo-based ΔR2* map reflects the BV changes in a broad range of vessel sizes, while the spin echo-based ΔR2 map reflects BV changes primarily in small vessels (e.g. capillaries and venules). These two parameters can be further derived to provide information on vessel size (ΔR2* /ΔR2) and density (ΔR2/(ΔR2*)2/3). The purpose of this dissertation is to develop and validate the advanced perfusion MRI techniques to study angiogenesis. It is divided into two parts. First, we apply the dynamic contrast enhanced MRI (DCE-MRI) and SSCE-MRI techniques to investigate the postischemic change of vascular permeability, cerebral BV (CBV), vessel size and density in relation to evolving ischemia-induced angiogenesis over the course of 3 weeks, in a well-defined three-vessel occlusion model in the rat and the results were validated by immunohistology. Second, since the current angiographic methods of visualizing blood vessels in the clinical setting are excellent for evaluating larger arteries and veins but not the small vessels such as arterioles and venules, we developed a CBV-based microscopic magnetic resonance angiography technique, termed 3DΔR2-mMRA, which can simultaneously provide high-resolution 3D information on the cerebral anatomy, in vivo microvascular architecture, and hemodynamic response. Several findings are interesting and valuable in our results. First, we reported a prolonged increase in vascular permeability from day 3 to day 21 postischemia, in particular the reperfused outer cortical layers and leptomeninges. Increased CBV was observed from day 3 to day 14, whereas increased CBV in small vessels, primarily capillaries, was noticed from day 7 to day 14, in the reperfused cortex. An initial drop in vascular density and a reciprocal increase in vessel size were observed within the reperfused cortex at day 1 and day 3 postischemia. Immunohistological analysis confirmed a similar decrease in microvessel density and increase in vessel size. Second, proposed microscopy MRA method with the advantage of less geometric artifacts can depict small vessels and trace individual vessel in normal and pathological tissue. In summary, this dissertation successfully demonstrated the ability of SSCE-MRI and 3DΔR2-mMRA can provide the information of microvascular structure and function that may be useful to understand hemodynamic mechanisms of cerebro-vascular diseases and in assessing the efficacy of therapeutic strategies directed at angiogenesis.