MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials

Abstract

SUMMARY: Murine models are the most commonly used and best investigated among the animal models of HGG. They constitute an important weapon in the development and testing of new anticancer drugs and have long been used in preclinical trials. Neuroimaging methods, particularly MR imaging, offer important advantages for the evaluation of treatment response: shorter and more reliable treatment end points and insight on tumor biology and physiology through the use of functional imaging DWI, PWI, BOLD, and MR spectroscopy. This functional information has been progressively consolidated as a surrogate marker of tumor biology and genetics and may play a pivotal role in the assessment of specifically targeted drugs, both in clinical and preclinical trials. The purpose of this Research Perspectives was to compile, summarize, and critically assess the available information on the neuroimaging features of different murine models of HGGs, and explain how these correlate with human disease and reflect tumor biology.ABBREVIATIONS: AIF ϭ arterial input function; ATP ϭ adenosine triphosphate; BOLD ϭ blood oxygen level-dependent; DCE ϭ dynamic contrast-enhanced; DSC ϭ dynamic susceptibility contrast; FLASH ϭ fast low-angle shot; gadolinium-DTPA ϭ gadolinium-diethylene-triamine pentaacetic acid; GEMM ϭ genetically engineered mouse model; GRE ϭ gradient recalled-echo; HGG ϭ high-grade glioma; MMP2 ϭ matrix metalloproteinase type 2; MVD ϭ mean vascular density; rCBVϭ relative cerebral blood volume; VEGF ϭ vascular endothelial growth factor A nimal models of HGG have become an imperative tool in the development and testing of new anticancer drugs. The combination of these advanced neuroimaging methods provides a novel integrated environment in which a collection of noninvasive biomarkers validated on well-defined animal models may provide important clues to tumor biology and response to treatment, with potential applications in human neoplasms. In general, the use of animal models overcomes many of the limitations found in the clinical setting, including impracticable serial tissue sampling and difficulties in establishing correlations between tumor physiopathology and its genetic profile, a circumstance limiting considerably the successful implementation of tailored personalized cancer treatments.Among neuroimaging methods, MR imaging is the most common technique to assist the management of patients with brain tumors; it is free of ionizing radiation, overall well-tolerated, and provides detailed anatomic and functional information. Neuroimaging features of murine models of HGG have been less explored due to technical limitations. Highresolution MR imaging of small animals requires high-field magnets with small bores and dedicated coils, adequate anesthesia, and tailored fixation devices (Fig 1).Murines are the most commonly used and are the best investigated models of human glioma. They are easy to handle, have a short life span, and develop central nervous system tumors that are similar to their human counterparts.1,2 Moreover, t...

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