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T2 weighted MRI for assessing renal lesions in transgenic mouse models of tuberous sclerosis
Maria Kalogerou1, Yadan Zhang, Jian Yang
1Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Objective:
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.
Materials And Methods:
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.
Results:
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%).
Conclusion:
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.
Insights
T2 weighted MRI can detect tuberous sclerosis (TSC) renal lesions in mouse models. While effective for cysts, MRI needs improved sensitivity for solid tumors in pre-clinical TSC research.
Area of Science:
- Biomedical imaging
- Pre-clinical research
- Genetics and disease modeling
Background:
- Tuberous sclerosis (TSC) is a genetic disorder characterized by the development of various tumors, particularly in the kidneys.
- Transgenic mouse models are crucial for studying TSC pathogenesis and evaluating therapeutic interventions.
- Accurate in vivo assessment of renal lesions is vital for pre-clinical trials in TSC.
Purpose of the Study:
- To evaluate the efficacy of T2 weighted magnetic resonance imaging (MRI) for detecting and characterizing renal lesions in mouse models of tuberous sclerosis.
- To compare MRI findings with histological analysis for comprehensive lesion assessment.
Main Methods:
- T2 weighted MRI scans were performed on Tsc1(+/-) and Tsc2(+/-) mice at baseline and after a 2-month interval.
- One Tsc2(+/-) mouse received rapamycin treatment between scans.
- Post-scan, mice were sacrificed, and MRI data were correlated with renal histology.
Main Results:
- T2 weighted MRI successfully identified all types of TSC-associated renal lesions, with a minimum detectable size of <0.1 mm³.
- Lesions showed significant growth in untreated mice and shrinkage in the rapamycin-treated mouse over the 2-month period.
- MRI detected 66% of cysts and cystadenomas but only 29% of solid tumors compared to histology.
Conclusions:
- T2 weighted MRI shows promise as a tool for assessing certain renal lesions in pre-clinical TSC studies.
- Enhanced MRI sensitivity is necessary for accurate detection of solid renal tumors in these models.
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