The effect of resolvin D in the treatment of vulnerable atherosclerotic plaque using in vivo magnetic resonance imaging in a rabbit model
Chapel, Andrew Jacob
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Serial high resolution in vivo magnetic resonance imaging (MRI) is a relatively new, powerful imaging method used to investigate atherosclerotic plaque progression in a rabbit model. This thesis studied the potential of Resolvin 01, an endogenous mediator of inflammation, to reduce high-risk or vulnerable plaque formation or to protect against plaque rupture as predicted by MRI measurements. A total of 4 New Zealand White Rabbits were fed a 1% high cholesterol chow diet for an 8-week period and had balloon catheter surgery performed to disrupt endothelial cells in the aorta in week 2. Three rabbits were treated with the endogenous inflammatory mediator Resolvin 01 for a 4 week period. Only two rabbits survived the entire experimental timeline. The rabbits were imaged noninvasively at 5 time points throughout the study. The contrast enhanced MR Angiography (MRA) data on the aorta of the rabbits demonstrated a remodeling ratio that remained level during the high cholesterol diet period, not determining that atherosclerotic plaques were progressing towards vulnerable plaques. MRA data produced positive remodeling in one rabbit during the treatment period signifying possible high-risk plaque formation. T1 black blood MRI data of the two rabbit aortas displayed a slight decrease in plaque area over the high cholesterol diet period followed by a slight increase during the Resolvin D1treatment period. MRI data also showed an increase in gadolinium uptake during the high cholesterol diet, followed by a decreased of gadolinium uptake during the treatment period in both rabbits. Neither rabbit that survived the experimental timeline suffered an atherosclerotic plaque rupture. In conclusion, this thesis supports the usefulness of MRI as a tool to investigate atherosclerotic plaque progression using a rabbit model. Additionally the results demonstrate the potential of Resolvin 01, an endogenous inflammatory mediator, as a prospective modulator capable of reducing high-risk plaque formation and of protecting against plaque rupture.
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