Renal Morphology and Cytoarchitecture in AT1-Deficient Mice Characterized by MRI
Luke Xie, Matthew A. Sparks, Wei Li, Yi Qi, Chunlei Liu, Thomas M. Coffman, G. Allan Johnson
NMR in Biomedicine 26(12): 1853-1863, 2013 PMCID: PMC3956055
The major functions of the kidney include filtration, reabsorption, secretion, and hormonal regulation. Disruption of key regulatory roles leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies, however quantifying or even detecting focal lesions due to inflammation and fibrosis has been challenging. We propose that quantitative susceptibility mapping (QSM) can be particularly sensitive for identifying inflammation and fibrosis in the kidney. In this study, we applied QSM in a mouse model deficient of angiotensin receptor type 1 (AT1). This model is known for its graded pathologies including focal areas of interstitial fibrosis, cortical inflammation, glomerular cysts, and inner medullary hypoplasia. We acquired high-resolution MRI on kidney specimens from AT1 deficient mice. Two MR sequences were used (3D spin echo and gradient echo) to produce three image contrasts<97>T1, T2* (magnitude), and QSM. The additional T1 and T2* (magnitude) images were acquired to segment major renal structures and provide landmarks for the focal lesions of inflammation and fibrosis in the 3D space. Focal lesions were segmented from QSM images and found to be closely associated with the major vessels. Susceptibility values from QSM were measured in renal regions and were found to be diamagnetic. This result was consistent with the increase of diamagnetic content, e.g., proteins and lipids, associated with inflammation and fibrosis. Focal lesions were validated with conventional histology. We found that QSM was very sensitive in detecting pathology due to small focal inflammation and fibrosis. QSM offers a new MR contrast mechanism to study this common disease marker in the kidney.
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The authors wish to thank Gary Cofer for technical assistance, Martin C. Fischer for microscopy, and Sally Zimney for editorial assistance. The authors also wish to thank members of the Duke Center for In Vivo Microscopy for their discussions and contributions. All work was in part supported by the NIH/NIBIB national Biomedical Technology Resource Center (P41 EB015897), NCI (U24 CA092656), and NIBIB (T32 GM008555).