Supporting Information and Data for:
4D MRI of polycystic kidneys from Rapamycin-treated Glis3-deficient mice
Luke Xie1,2, Yi Qi2, Ergys Subashi1,3, Grace Liao4, Laura Miller-DeGraff4, Anton M. Jetten4, G. Allan Johnson1,2
1Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 277102Department of Biomedical Engineering, Duke University, Durham, NC 27708
3Medical Physics Graduate Program, Duke University, Durham, NC 27710
4Cell Biology Section, Division of Intramural Research, NIH / NIEHS, Research Triangle Park, NC 27709
NMR in Biomedicine 2015 May;28(5):546-554 PMCID: PMC4400264
Polycystic kidney disease (PKD) is a life-threatening disease that leads to a grotesque enlargement of the kidney and significant lose of function. Several imaging studies with MRI have demonstrated that cyst size in polycystic kidneys can determine disease severity and progression. In the present study, we found that while kidney volume and cyst volume decreased with drug treatment, renal function did not improve with treatment. Here, we applied dynamic contrast-enhanced MRI to study PKD in a Glis3-deficient mouse model. Cysts from this model have a wide range of sizes and develop at an early age. To capture this crucial stage and assess cysts in detail, we imaged during early development (3 to 17 weeks) and applied high spatiotemporal resolution MRI (125x125x125 cubic microns every 7.7 seconds). A drug treatment with Rapamycin was applied to determine whether disease progression could be halted. The effect and interaction of aging and treatment were evaluated using an analysis of variance. Structural measurements including kidney volume, cyst volume, and cyst-kidney volume ratio changed significantly with age. Drug treatment significantly decreased these metrics. Functional measurements, including time-to-peak (TTP) sum and mean, did not change with age, while TTP variance increased with age. However, the treatment of Rapamycin generally did not affect these functional metrics. Synergistic effects of treatment and age were not found for any measurements. Together, the size and volume ratio of cysts decreased with drug treatment, while renal function remained the same. Quantifying renal structure and function with MR imaging biomarkers can comprehensively assess the pathophysiology of PKD and response to treatment.
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All imaging was performed at the Duke Center for In Vivo Microscopy, an NIH/NIBIB National Biomedical Technology Resource Center (P41 EB015897).