Abstract

Background: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.Methods: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. T2-weighted imaging, quantitation of the native longitudinal relaxation time (T1) and the transverse relaxation rate (R2*), and dynamic contrast-enhanced (DCE)-MRI, was used to assess tumour volume, phenotype and response to cyclophosphamide or cabozantinib.Results:Excellent T2-weighted image contrast enabled clear tumour delineation at 3T. Significant correlations of tumour volume (R=0.98, P<0.0001) and R2* (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 R2* (P<0.001), consistent with impaired tumour perfusion. DCE-MRI was performed simultaneously on three transgenic mice, yielding estimates of Ktrans for each tumour (median Ktrans values of 0.202, 0.168 and 0.114 min−1). Cyclophosphamide elicited a significant reduction in both tumour burden (P<0.002) and native T1 (P<0.01), whereas cabozantinib induced significant (P<0.01) tumour growth delay.Conclusions: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.

Highlights

  • The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with clinical studies

  • The use of clinical scanners to conduct pre-clinical research is attractive, as it facilitates a more direct comparison with clinical studies, the application and development of clinically applicable imaging protocols, matching of field strength-related mechanisms such as relaxation, and provides evidence to support the clinical relevance of functional MRI data/ biomarkers

  • MRI of GEM tumour models on a clinical 3T scanner et al, 2007; Linn et al, 2007; Bilgen, 2013). This approach benefits from the hardware and software advances continuously being made on modern clinical MRI systems, such as parallel transmit and receive technology, motion and contrast tracking, k-space under-sampling and view-sharing strategies (Ullman et al, 2004; Wech et al, 2012; Jerome et al, 2016)

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Summary

Objectives

The purpose of this study was to evaluate the utility and sensitivity of a non-bespoke high resolution RF coil for use on a clinical 3T scanner for the acquisition of anatomical and functional MRI data/biomarkers from transgenic mouse models of neuroblastoma in vivo

Methods
Results
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Conclusion

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