Pre-clinical imaging of transgenic mouse models of neuroblastoma using a dedicated 3-element solenoid coil on a clinical 3T platform

Br J Cancer. 2017 Sep 5;117(6):791-800. doi: 10.1038/bjc.2017.251. Epub 2017 Aug 8.

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.

Publication types

  • Evaluation Study

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Anilides / therapeutic use
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Contrast Media
  • Cyclophosphamide / therapeutic use
  • Disease Models, Animal
  • Female
  • Magnetic Resonance Imaging / instrumentation
  • Magnetic Resonance Imaging / methods*
  • Magnets*
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation
  • N-Myc Proto-Oncogene Protein / metabolism
  • Neuroblastoma / diagnostic imaging*
  • Neuroblastoma / drug therapy
  • Neuroblastoma / genetics
  • Neuroblastoma / pathology
  • Phantoms, Imaging
  • Phenotype
  • Pyridines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / genetics
  • Signal-To-Noise Ratio
  • Stomach Neoplasms / diagnostic imaging*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Tumor Burden / drug effects

Substances

  • Anilides
  • Antineoplastic Agents
  • Contrast Media
  • MYCN protein, mouse
  • N-Myc Proto-Oncogene Protein
  • Pyridines
  • cabozantinib
  • Cyclophosphamide
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases