Abstract 1488: In vivo magnetic resonance elastography in pediatric brain tumor models

Abstract

Abstract Refined imaging strategies that could improve diagnosis and management of children with brain malignancies are urgently required. Pediatric brain malignancies possess distinct underlying biologies that discriminate them from adult tumors, even within a common neuropathological diagnosis such as glioblastoma (GBM). Magnetic resonance elastography (MRE) exploits the ability of MRI to visualize the propagation of shear waves resulting from vibrations applied to the cranium to map and quantify (kPa) brain tissue elasticity (Gd) and viscosity (Gl) in vivo. The altered viscoelastic properties of tumors, combined with the sensitivity of MRE for differences in tumor microstructure, establishes MRE as an attractive modality for the detection and differential diagnosis of brain malignancies. Here we aimed to determine whether the potential of MRE in the neuroradiological management of patients with brain malignancies could be extended to the pediatric population. The viscoelastic properties of two pediatric brain tumor models that faithfully emulate high risk childhood disease were investigated: i) Orthotopic D-212 MG pediatric supratentorial giant cell GBM (H3F3A wildtype, 11 year old patient) xenografts propagated in NCr nu/nu mice and ii) GTML/Trp53KI/KI transgenic mice that spontaneously develop aggressive, MYCN driven, p53 depleted, medulloblastomas. D-212 MG and GTML/Trp53KI/KI tumors were less elastic (lower Gd) and viscous (lower Gl), and therefore softer, than the surrounding brain tissue. Both tumor types were also significantly less elastic (D-212 MG Gd = 3.9±0.2; GTML/Trp53KI/KI Gd = 3.5±0.1) than the soft thalamic parenchyma in non-tumor-bearing mice (Gd = 5.9±0.2; p = 0.001 and p = 0.02, respectively, Mann-Whitney), in addition to being less viscous. Interestingly, GTML/Trp53KI/KI tumors demonstrated a bimodal distribution of Gd, which reflected the more marked transition between their relatively stiffer rim and the softer core compared with D-212 MG tumors. We demonstrate that two representative models of major high risk pediatric brain malignancies share the unique softness previously observed in adult brain tumor models, allowing their detection by MRE. This supports observations that pediatric GBMs are morphologically indistinguishable from adult GBMs. Although median Gd values were not sufficient to discriminate between the tumor types, the marked bimodal distribution of Gd in the GTML/Trp53KI/KI tumors was not apparent in D-212 MG GBM tumors. Whilst ongoing histopathological investigation into growth patterns, vascular, cellular and extracellular networks will aid elucidation of the pathological determinants of the bimodal signature, to date unique to GTML/Trp53KI/KI, these data reinforce the potential of MRE for the detection and differential diagnosis of pediatric brain malignancies based on their mechanical properties. Citation Format: Jin Li, Jessica K.R. Boult, Maria Vinci, Sergey Popov, Karen Barker, Zai Ahmad, Yann Jamin, Craig Cummings, Suzanne A. Eccles, Jeffrey C. Bamber, Ralph Sinkus, Louis Chesler, Chris Jones, Simon P. Robinson. In vivo magnetic resonance elastography in pediatric brain tumor models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1488. doi:10.1158/1538-7445.AM2015-1488