Renal Lipids and Oxygenation in Diabetic Mice: Noninvasive Quantification with MR Imaging

Abstract

To determine the relationship between renal lipid content and intrarenal oxygenation in diabetic nephropathy by using noninvasive chemical shift-selective (CSS) imaging and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. The study was approved by the institutional Committee on Animal Research. Lipid and water phantoms for CSS imaging were made, and BOLD MR imaging phantoms from arterial and venous blood samples were collected from rats. CSS imaging and BOLD imaging were performed to measure lipid contents and T2* in phantoms and kidneys of diabetic gene (db) db/db mice and wild-type mice after exposure to nitrogen (four per group) and injection of furosemide (four per group). Results of MR imaging-measured lipid contents and oxygen tension were compared with known values in phantoms and reference standard from mice with histologic data. Statistical analysis was performed with independent sample and paired sample t tests and Pearson correlation test. Renal lipid content in db/db mice was significantly higher compared with that in control mice (9.40% ± 1.89 and 3.11% ± 0.57, respectively; P < .001). In addition, the lipid content in the cortex of db/db mice was significantly higher than that in medulla (12.73% ± 0.94 and 3.16% ± 0.50, respectively; P < .001). Correlation was significant between T2* measured with BOLD and oxygen tension in blood phantoms (r = 0.958; P < .001). Lower baseline T2* in diabetic kidney suggested lower oxygenation that reserved excess oxygen supply. Lower oxygenation in diabetic kidney cortex was observed after nitrogen exposure and furosemide injection. Noninvasive CSS imaging and MR imaging of db/db diabetic mice revealed the relationship between the renal lipid content and intrarenal oxygenation in diabetic kidney. Lipid accumulation in diabetic kidney compromises the oxygenation of the renal tissue and made it more susceptible to renal hypoxia. Online supplemental material is available for this article.