Novel MRI Imaging Biomarkers for Diabetic Complications
Katherine Dell   (Cleveland, OH)
Type II diabetes mellitus (DM) affects millions of people worldwide and causes a myriad of complications that affect multiple organs in the body, including kidneys, heart, vasculature, gastrointestinal system, skin and eyes. These complications contribute to significant morbidity and mortality in diabetic patients; however, not all patients with DM these complications. Thus, it is of utmost importance to detect complications at the early stages of disease before irreversible damage has occurred, so that specific interventions can be targeted to high risk populations. Unfortunately, many of the clinical indicators of "end-organ" involvement are not evident until substantial damage has occurred. This challenge highlights the importance of developing non-invasive, clinically applicable biomarkers of early disease. Newer, quantitative magnetic resonance imaging (MRI) techniques, such as Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) and Magnetization Transfer MRI (MT-MRI), have the potential to detect early disease but have not been rigorously studied in human or animal models of DM. The proposed studies will apply these quantitative techniques to the study of two diabetic complications: diabetic nephropathy (DN) and non-alcoholic fatty liver disease (NAFLD). The overall hypothesis is that MRI imaging techniques can be used as quantitative biomarkers to monitor progression of diabetic and kidney and liver disease in the early stages of disease. The proposed studies will use the db/db mouse, a well-characterized DM model that develops features of DN and fatty liver disease. The specific aim of the proposal to develop MRI imaging techniques to assess the development of nephropathy and fatty liver disease in the db/db mouse. Db/db animals will be imaged serially at different ages using the quantitative MRI imaging techniques, MT-MRI (to assess kidney collagen and hypertrophy) and IDEAL (to assess liver fat deposition). MRI results will be correlated with histologic/biochemical and clinical assessments, in order to determine the applicability of these techniques to detecting early kidney and liver disease and monitoring disease progression.