Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Eur J Radiol. 2012 Sep;81(9):2069-74. doi: 10.1016/j.ejrad.2011.06.054. Epub 2011 Jul 28.
Transgenic mouse models of tuberous sclerosis (TSC) develop renal cysts, cystadenomas, solid adenomas and carcinomas. Identification and characterisation of these lesions in vivo may help in TSC pre-clinical trials. This study was to evaluate T2 weighted MRI for assessment of renal lesions in two Tsc mouse models.
Tsc1(+/-), Tsc2(+/-) and wild type mice were subjected to a first MRI scan at 12 months of age and a second scan 2 months later. One Tsc2(+/-) mouse was treated with rapamycin for two months after the initial scan. Immediately following the second scan, mice were sacrificed and MRI images were compared to renal histological findings.
MRI identified all types of Tsc-associated renal lesions in both Tsc1(+/-) and Tsc2(+/-) mice. The smallest detectable lesions were <0.1 mm(3). Eighty three percent of all renal lesions detected in the first scan were re-identified in the second scan. By MRI, these lesions demonstrated significant growth in the 9 untreated Tsc1(+/-) and Tsc2(+/-) mice but shrinkage in the rapamycin treated Tsc2(+/-) mouse. Between the two scans, MRI also revealed significant increase in both the total number and volume of lesions in untreated mice and decrease in the rapamycin treated mouse, respectively. In comparison to histological analysis MRI detected most cysts and cystadenomas (66%) but only a minority of solid tumours (29%).
These results suggest that T2 weighted MRI may be a useful tool for assessing some renal lesions in pre-clinical studies using Tsc mouse models. However, improved sensitivity for T2 weighted MRI is required, particularly for solid renal lesions.
结节性硬化症(TSC)的转基因小鼠模型会发展出肾囊肿、囊腺瘤、实体腺瘤和癌。在体内识别和描述这些病变可能有助于 TSC 的临床前试验。本研究旨在评估 T2 加权 MRI 用于评估两种 Tsc 小鼠模型的肾脏病变。
Tsc1(+/-)、Tsc2(+/-)和野生型小鼠在 12 个月大时进行第一次 MRI 扫描,两个月后进行第二次扫描。在初次扫描后,一只 Tsc2(+/-)小鼠接受雷帕霉素治疗两个月。第二次扫描后,立即处死小鼠,将 MRI 图像与肾脏组织学发现进行比较。
MRI 在 Tsc1(+/-)和 Tsc2(+/-)小鼠中均能识别出所有类型的 Tsc 相关肾脏病变。最小可检测病变<0.1mm(3)。第一次扫描中检测到的 83%的所有肾脏病变在第二次扫描中均被重新识别。通过 MRI,这些病变在未接受治疗的 9 只 Tsc1(+/-)和 Tsc2(+/-)小鼠中明显生长,但在接受雷帕霉素治疗的 Tsc2(+/-)小鼠中缩小。在两次扫描之间,MRI 还分别显示出未接受治疗的小鼠中病变的总数和体积显著增加,而接受雷帕霉素治疗的小鼠中则减少。与组织学分析相比,MRI 检测到大多数囊肿和囊腺瘤(66%),但只有少数实体瘤(29%)。
这些结果表明,T2 加权 MRI 可能是使用 Tsc 小鼠模型进行临床前研究评估某些肾脏病变的有用工具。然而,需要提高 T2 加权 MRI 的灵敏度,特别是对实体肾脏病变。