Xie Luke, Qi Yi, Subashi Ergys, Liao Grace, Miller-DeGraff Laura, Jetten Anton M, Johnson G Allan
Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
NMR Biomed. 2015 May;28(5):546-54. doi: 10.1002/nbm.3281. Epub 2015 Mar 23.
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.
多囊肾病（PKD）是一种危及生命的疾病，会导致肾脏异常肿大并严重丧失功能。多项MRI成像研究表明，多囊肾囊肿的大小可决定疾病的严重程度和进展。在本研究中，我们发现，尽管药物治疗后肾脏体积和囊肿体积减小，但肾功能并未因治疗而改善。在此，我们应用动态对比增强MRI来研究Glis3（GLI相似3）基因缺陷小鼠模型中的PKD。该模型中的囊肿大小各异且在幼年时就开始形成。为了捕捉这一关键阶段并详细评估囊肿，我们在早期发育阶段（3 - 17周）进行成像，并应用高时空分辨率MRI（每7.7秒采集一次125×125×125立方微米的数据）。应用雷帕霉素（也称为西罗莫司）进行药物治疗，以确定疾病进展是否可以停止。使用方差分析（ANOVA）评估衰老与治疗的效果及协同作用（相互作用）。包括肾脏体积、囊肿体积和囊肿与肾脏体积比在内的结构测量值随年龄显著变化。药物治疗使这些指标显著降低。测定了达峰时间（TTP）均值和TTP方差的功能测量值。TTP均值不随年龄变化，而TTP方差随年龄增加。雷帕霉素治疗一般不影响这些功能指标。在任何测量中均未发现治疗与年龄的协同作用。总之，药物治疗使囊肿的大小和体积比减小，而肾功能保持不变。MRI对肾脏结构和功能的定量分析可全面评估PKD的病理生理学及对治疗的反应。
