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Magnetic Resonance Histology of Age-related Nephropathy in Sprague-Dawley Rats

Luke Xie, Rachel Cianciolo, Brian Hulette, Ha Won Lee, Yi Qi, Gary Cofer, G. Allan Johnson

Toxicologic Pathology 40(5):764-778, 2012

Magnetic resonance histology (MRH) has become a valuable tool in evaluating drug-induced toxicity in preclinical models. However, the application in renal injury has been limited. This study was designed to help understand the background pathology created by chronic disease, inflammation, or age-related de-generation in the kidney laying the foundation for more extensive use in drug toxicity evaluation. This study demonstrates the use of MRH to study the entire intact kidney in a spontaneous model of chronic kidney aged-associated nephropathy. Kidneys from male Sprague-Dawley rats were imaged at 8 weeks (n=4) and 52 weeks (n=4) on a 9.4T system dedicated to MR microscopy. Several potential contrast mechanisms were explored to optimize the scanning protocols. Full coverage of the entire kidney was achieved with isotropic spatial resolution at 31 microns (voxel volume =30 pl) using a gradient recalled echo. Isotropic spatial resolution down to 15.6 microns (voxel volume < 4 pl) was achieved over a smaller field of view. Qualitative age-related structural changes were apparent in the renal cortical microvascula-ture, tubule and interstitial fibrosis, and glomerular architecture. The nondestructive three-dimensional images allowed us to measure quantitative differences of the kidney volume, pelvis volume, main vessel volume, glomerular size, and thickness of the cortex, outer medulla, and inner medulla.

The authors wish to thank Sina Farsiu, Stephanie Chiu, Sally Gewalt, Brian Berridge, Larry Hedlund, Samuel Johnston, and Sally Zimney for their discussions, contributions, and editorial work. All work was performed at the Duke Center for In Vivo Microscopy, an NIBIB National Biomedical Technology Resource Center (P41 EB015897), with additional funding from NCI U24 CA092656 and NIBIB T32 GM008555.

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  • All work was performed at the Duke Center for In Vivo Microscopy, an NIH/NCRR national Biomedical Technology Research Center (P41 RR005959), with additional support from NCI (R01_CA_14282). We thank Sally Zimney for editorial work.