Assessment of Peripheral Microcirculation using Magnetic Resonance Imaging

This thesis describes the development of a new measurement and analysis tool to assess the microcirculation in limb ischemia. Peripheral arterial disease (PAD) is diagnosed by reduced bulk blood flow and blood pressures in the legs. Patients with severe limb ischemia have limited walking ability and may experience rest pain or foot ulceration. PAD can be treated with revascularization for their large-vessel diseases. However, some patients respond poorly to revascularization. It is hypothesized that the microvascular disease component of limb ischemia may contribute to the differential outcome of revascularization. Therefore, this project is motivated to probe peripheral microvascular perfusion and to investigate the related vascular physiology and clinical indications of limb ischemia. A magnetic resonance imaging-based technique, called arterial spin labeling (ASL), was developed to characterize the dynamic perfusion response to brief periods of flow interruption. In a group of healthy subjects, the technique captured the changes of calf muscle reactive hyperemia with respect to the different durations of flow interruption, reflecting the microvascular function in regulating perfusion for different amounts of metabolic stresses. In addition, the technique also captured the differences between patients with PAD and healthy subjects in the dynamic characteristics of reactive hyperemic responses. Next, a quantitative physiological model, incorporating the influences of arterial stenoses and microvascular dysfunction, was established to facilitate the physiological interpretation of ASL reactive hyperemia. Model-derived perfusion indices were compared between subject groups. Patients were found to have higher arterial resistance and lower microvascular sensitivity to hypoxia than the healthy subject group. Finally, the perfusion measures were compared with symptom severity and functional outcome 6-month following successful endovascular revascularization in a cohort of patients. Measures of arterial resistance were related to the manifested severity, whereas the microvascular sensitivity index appeared to differentiate prognosis following revascularization. Overall, this thesis improved the ASL method to assess peripheral muscle perfusion and demonstrated the clinical relevance of perfusion measures to symptom severity and revascularization outcome of PAD for the first time. A future study with a larger patient population and longer follow-up period will be required to confirm the current findings.Ph.D