The glioblastoma biomechanical landscape: A systematic review of magnetic resonance elastography (MRE) of brain tumors and healthy brain.

Abstract

Diagnosis of a glioblastoma (GBM) brain tumor is associated with very poor prognosis. Currently, few preclinical models used to identify new therapies address the soft brain tissue environment and GBM mechanoresponses, which are implicated in disease progression. Understanding the GBM biomechanical landscape is critical to deriving improved preclinical models and magnetic resonance elastography (MRE) holds promise to address this gap. Due to technical and feasibility issues for MRE of patient tumors at scale, most studies only report on small cohorts of patients, thus limiting the conclusions that may be drawn from individual studies. To thus gain a better overview, we have undertaken a systematic review and meta-analysis of the reported tissue viscoelastic property values from studies of both healthy brain and brain tumors, with a particular focus on delineating measurements relative to MRE transducer vibration frequency. Based on these analyses, healthy white matter consistently appears stiffer than gray matter. Further, analyses of pooled healthy brain tissue measurements vs human GBM suggested that, overall, the GBM has the same stiffness as the surrounding healthy tissue. This contrasted with mouse models of GBM, where the tumors appear softer than brain tissue. The limited number of studies of human GBM in situ is a caveat to these conclusions and MRE analyses of larger GBM patient cohorts are urgently needed. Meanwhile, the information from this analysis can be used to guide engineering of improved preclinical models with features that recapitulate the in vivo brain tissue environment.