Imaging of tissue injury-repair addressing the significance of oxygen and its derivatives
The purpose of this work was to study tissue injury-repair using non-invasive biomedical imaging techniques. We employed Magnetic Resonance Imaging (MRI) to evaluate the effect of focal ischemic insult to brain and heart in rodent models. Electron Paramagnetic Resonance (EPR) Spectroscopy was used to study dermal wound healing in mouse models of excisional wounds. A robust Middle Cerebral Artery Occlusion model of focal cerebral ischemia in rodents was established. Serial evaluation of ischemic damage showed that MRI characteristics of ischemic regions change dynamically in the reperfusion period. It was concluded that prevention of vasogenic edema after ischemia is a valuable therapeutic target, and treatment efficacy may be evaluated with MRI. To assess the redox environment of dermal wound site in vivo, a novel EPR based approach was standardized. Non-invasive measurements of metabolism of topically applied nitroxide 15N-perdeuterated tempone in murine excisional dermal wounds demonstrated that the wound site is rich in oxidants, the level of which peaked two day post-wounding in the inflammatory phase. Using Rac2-deficient mice it was concluded that rac2 significantly contributes to oxidant production at the wound site supporting the healing process. High resolution (11.7T) cardiac MRI and histological approaches were employed in tandem to characterize the progressive secondary damage suffered by the murine myocardium following the initial insult caused by ischemia-reperfusion (IR). IR induced changes in the myocardium were examined at specific time-points post reperfusion. A progressive loss of myocardial function associated with increased infarct volume and worsened regional wall motion was observed both with MRI and histological approaches. It was established that myocardial remodeling following IR included progressive myocardial tissue damage which was tightly associated with loss of cardiac function. The final objective of this dissertation was to test the functional significance of tissue remodeling process induced by hyperoxic shock in the heart in a mouse IR model. Worst cardiac function post IR was observed in animals that suffered highest hyperoxic shock, and lowest loss of function in animals with least shock. The p21 pathway was implicated as a major player in the induction of perceived hyperoxic shock and its functional effects.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:biomedical imaging magnetic resonance electron paramagnetic stroke cardiac remodeling wound healing
Date of Publication:01/01/2007