In this work, the applicant proposes to develop the skills necessary for effective technology development and clinical efficacy evaluation based on a specific imaging model: Magnetic Resonance Angiography (MRA) and Doppler Ultrasound (DUS) for the detection and evaluation of renal vascular disease. The objective of this proposal is to provide the support necessary for Dr. Grist to cultivate an independent research program aimed at the development and subsequent clinical evaluation of new imaging technologies. Although the applicant intends to continue his work involving development of new MR imaging techniques, a major emphasis of this proposal is to develop the skills necessary to perform clinical efficacy studies. These skills will be acquired through a combination of didactic courses at the University of Wisconsin, application of the techniques to the proposed research program, and mentorship by the applicant's sponsors and academic advisor. The research plan for developing these skills encompasses two phases. In the first phase the model will be used in order to assess the technical merit and diagnostic accuracy of renal MRA and DUS studies. In the second phase, the imaging studies will be used as a focal point to develop strategies to evaluate clinical efficacy of the techniques. In the second phase, we specifically aim to determine the value of DUS and quantitative MR techniques for predicting the functional significance of stenoses in patients with rapidly progressive renal failure where renovascular disease is a suspected etiology. To evaluate the first objective, MR angiograms will be obtained in a group of patients (n=22) using several new MRA techniques in our laboratory. After an optimal screening technique is identified, MRA and DUS studies will be performed in a large group of patients referred to conventional arteriography for evaluation of atherosclerotic vascular disease elsewhere. A blinded, prospective comparison of MRA, DUS and conventional arteriography will be performed in 100 patients using a consensus reading of the conventional arteriogram as the gold standard. In order to evaluate the functional significance of stenoses, a group of 146 patients with rapidly progressive renal failure will be evaluated using the MRA and DUS techniques. The gold standard for renal failure due to renal artery stenoses will be established based on clinical follow-up and response to revascularization therapy. The imaging data will be correlated with extensive clinical data acquired during patient management. A consensus determination of the presence of disease and patient outcome will be performed by a panel including the radiologist, nephrologist, and vascular surgeon involved in the care of the patient. The research proposal facilitates an interdisciplinary environment in which the applicant may address complex basic science and clinical issues related to renovascular disease with the guidance of experienced clinical and basic science co-sponsors.
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