title: 4D MRI of polycystic kidneys from rapamycin-treated Glis3-deficient mice.
abstract: Polycystic kidney disease (PKD) is a life-threatening disease that leads to a grotesque enlargement of the kidney and significant loss 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, although 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 (GLI-similar 3)-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 (3-17 weeks) and applied high spatiotemporal resolution MRI (125 × 125 × 125 cubic microns every 7.7 s). A drug treatment with rapamycin (also known as sirolimus) was applied to determine whether disease progression could be halted. The effect and synergy (interaction) of aging and treatment were evaluated using an analysis of variance (ANOVA). Structural measurements, including kidney volume, cyst volume and cyst-to-kidney volume ratio, changed significantly with age. Drug treatment significantly decreased these metrics. Functional measurements of time-to-peak (TTP) mean and TTP variance were determined. TTP mean did not change with age, whereas TTP variance increased with age. Treatment with 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, whereas renal function remained the same. The quantification of renal structure and function with MRI can comprehensively assess the pathophysiology of PKD and response to treatment.
authors: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors: Luke
authors: L
authors: Xie
authors: Yi
authors: Y
authors: Qi
authors: Ergys
authors: E
authors: Subashi
authors: Grace
authors: G
authors: Liao
authors: Laura
authors: L
authors: Miller-DeGraff
authors: Anton M
authors: AM
authors: Jetten
authors: G Allan
authors: GA
authors: Johnson
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000473:pathology*; D012097:Repressor Proteins / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000627:therapeutic use*; D015534:Trans-Activators / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; C478000:Glis3 protein, mouse; D007166:Immunosuppressive Agents; D012097:Repressor Proteins; D015534:Trans-Activators; D020123:Sirolimus
keywords: Glis3 protein; MR microscopy; MRI; polycystic kidney disease; small animal preclinical imaging; three-dimensional dynamic contrast-enhanced