In vivo solid stress is associated with poor patient survival in glioma

Abstract: Solid stress is increasingly being recognized as a key driver of tumor progression and aggressiveness, yet it has not been directly measured in patients so far. Here, we combine multifrequency magnetic resonance elastography with 3D magnetic resonance imaging (MRI)-based diffeomorphic deformable image registration network analysis to noninvasively quantify glioma-induced solid stress. In both a mouse model and patients, we identified spatially heterogeneous deformation patterns extending well beyond tumor margins. While deformation magnitude was not found to correlate with tumor size or clinical outcome, excess solid stress - defined as the product of peritumoral volumetric strain and stiffness differential between unaffected brain and peritumoral tissue - was inversely associated with patient survival. To our knowledge, these findings provide the first in vivo indication that tumor-associated mechanical stress affects clinical outcomes and can thus serve as a quantitative, imaging-derived biomarker with potential utility for prognostication and treatment guidance in patients with glioma.