Pre-clinical imaging of transgenic mouse models of neuroblastoma using a dedicated 3-element solenoid coil on a clinical 3T platform.
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<h4>Background</h4>The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with clinical studies. Here the utility and sensitivity of anatomical and functional MRI data/biomarkers acquired from transgenic mouse models of neuroblastoma using a dedicated radiofrequency (RF) coil on a clinical 3T scanner was evaluated.<h4>Methods</h4>Multiparametric MRI of transgenic mice bearing abdominal neuroblastomas was performed at 3T, and data cross-referenced to that acquired from the same mice on a pre-clinical 7T MRI system. T<sub>2</sub>-weighted imaging, quantitation of the native longitudinal relaxation time (T<sub>1</sub>) and the transverse relaxation rate (R<sub>2</sub>*), and dynamic contrast-enhanced (DCE)-MRI, was used to assess tumour volume, phenotype and response to cyclophosphamide or cabozantinib.<h4>Results</h4>Excellent T<sub>2</sub>-weighted image contrast enabled clear tumour delineation at 3T. Significant correlations of tumour volume (R=0.98, P<0.0001) and R<sub>2</sub>* (R=0.87, P<0.002) measured at 3 and 7T were established. Mice with neuroblastomas harbouring the anaplastic lymphoma kinase mutation exhibited a significantly slower R<sub>2</sub>* (P<0.001), consistent with impaired tumour perfusion. DCE-MRI was performed simultaneously on three transgenic mice, yielding estimates of K<sup>trans</sup> for each tumour (median K<sup>trans</sup> values of 0.202, 0.168 and 0.114 min<sup>-1</sup>). Cyclophosphamide elicited a significant reduction in both tumour burden (P<0.002) and native T<sub>1</sub> (P<0.01), whereas cabozantinib induced significant (P<0.01) tumour growth delay.<h4>Conclusions</h4>Simultaneous multiparametric MRI of multiple tumour-bearing animals using this coil arrangement at 3T can provide high efficiency/throughput for both phenotypic characterisation and evaluation of novel therapeutics, and facilitate the introduction of functional MRI biomarkers into aligned imaging-embedded clinical trials.
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Disease Models, Animal
Receptor Protein-Tyrosine Kinases
Magnetic Resonance Imaging
N-Myc Proto-Oncogene Protein
Anaplastic Lymphoma Kinase
Paediatric Solid Tumour Biology and Therapeutics
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British journal of cancer, 2017, 117 (6), pp. 791 - 800