Diabetic nephropathy (DN) is a major diabetic complication that determines the morbidity and mortality of the diabetic patients

Diabetic nephropathy (DN) is a major diabetic complication that determines the morbidity and mortality of the diabetic patients. Although clinical indicators or risk factors of this disease have been described, the currently available tests do not reliably assess its severity or progression in individual patients, making it difficult to do the targeted and intensified treatment to high-risk patients. Renal fibrosis is a hallmark of progressive DN; therefore, it is critical to evaluate the presence and extent of renal fibrosis in the diabetic kidney to treat the patients as well as to predict their long-term outcome. However, the current clinical tests lack the sensitivity and specificity to measure renal fibrosis in diabetic kidney. Although renal biopsy can diagnose fibrosis, it is invasive and prone to sampling errors, and does not reliably measure renal fibrosis in the affected kidney. Thus, a non-invasive test that better evaluate renal fibrosis would greatly improve the assessment of this disease. In recent decade, a variety of magnetic resonance imaging (MRI) methods have been developed and applied to human disease including cancer and brain disorders. These techniques have enabled us to assess the pathological changes in disease organ at molecular and cellular levels. Magnetization transfer (MT) imaging is a MRI technique that evaluates large and immobile macromolecules distributed within the tissue and could provide a means to evaluate the pathological events that are accompanied by the changes of macromolecular components, such as fibrosis and apoptosis. However, this method is poorly applied to kidney disease including DN. Therefore, here we will evaluate the utility of MT imaging in measuring renal fibrosis in diabetic kidney using a mouse model of progressive DN (db/db eNOS -/- mice). The aims of this study are: 1) To optimize and establish the MT protocol for mouse kidney imaging; 2) To examine the correlation between MT data and histological or biochemical measures of renal fibrosis. Thus, this application explores a new MRI test to assess renal fibrosis in DN. Given the fact that this MRI technique can be translated to clinics, the present work should efficiently improve the outcome of the DN patients.