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

• Published in: British journal of cancer Vol. 117; no. 6; pp. 791 - 800
• Main Authors: Almeida, Gilberto S, Panek, Rafal, Hallsworth, Albert, Webber, Hannah, Papaevangelou, Efthymia, Boult, Jessica KR, Jamin, Yann, Chesler, Louis, Robinson, Simon P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-09-2017; Nature Publishing Group
• Subjects: 631/67/1857; 631/67/2321; Anaplastic Lymphoma Kinase; Anilides - therapeutic use; Animal models; Animals; Antineoplastic Agents - therapeutic use; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical trials; Contrast Media; Cyclophosphamide; Cyclophosphamide - therapeutic use; Delineation; Disease Models, Animal; Drug Resistance; Epidemiology; Female; Functional magnetic resonance imaging; Image contrast; Lymphoma; Magnetic Resonance Imaging - instrumentation; Magnetic Resonance Imaging - methods; Magnets; Male; Mice; Mice, Transgenic; Molecular Medicine; Mutation; N-Myc Proto-Oncogene Protein - metabolism; Neuroblastoma; Neuroblastoma - diagnostic imaging; Neuroblastoma - drug therapy; Neuroblastoma - genetics; Neuroblastoma - pathology; Oncology; Perfusion; Phantoms, Imaging; Phenotype; Protein-tyrosine kinase; Pyridines - therapeutic use; Quantitation; Radio frequency; Receptor Protein-Tyrosine Kinases - genetics; Relaxation time; Rodents; Signal-To-Noise Ratio; Stomach Neoplasms - diagnostic imaging; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Transgenic animals; Transgenic mice; Translational Therapeutics; Tumor Burden - drug effects; Tumors; neuroblastoma; murine model; MRI; clinical platform; cancer imaging; pre-clinical
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.251

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.
T
2
-weighted imaging, quantitation of the native longitudinal relaxation time (
T
1
) and the transverse relaxation rate (
R
2
*), and dynamic contrast-enhanced (DCE)-MRI, was used to assess tumour volume, phenotype and response to cyclophosphamide or cabozantinib.
Results:
Excellent
T
2
-weighted image contrast enabled clear tumour delineation at 3T. Significant correlations of tumour volume (
R
=0.98,
P
<0.0001) and
R
2
* (
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
2
* (
P
<0.001), consistent with impaired tumour perfusion. DCE-MRI was performed simultaneously on three transgenic mice, yielding estimates of
K
trans
for each tumour (median
K
trans
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
T
1
(
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.