Longitudinal multifrequency MR elastography reveals biomechanical signatures of progression in a translational liver tumor model

Conventional magnetic resonance imaging (MRI) often detects liver tumors after morphologic and vascular changes become apparent, whereas biomechanical alterations may precede visible tumor formation. Here, we evaluate multifrequency magnetic resonance elastography (mMRE)-derived shear wave speed (SWS) and phase angle (ϕ) covering stiffness and viscosity as non-invasive biomechanical imaging markers for liver cancer formation and progression in a translational rabbit model. VX2 liver tumor-bearing New Zealand White rabbits underwent five longitudinal multiparametric MRI scans over 14 days, including mMRE at clinically relevant frequencies on a 3 Tesla scanner. SWS and ϕ maps were compared with apparent diffusion coefficient (ADC) maps, histopathology, and proteomics. Tumor SWS and ϕ increased 2-3 days after implantation and were significantly higher than liver at two weeks (SWS: p = .002; ϕ: p = .008). Tumor ADC decreased significantly only from days 11-13 onward (day 14: p = .02). Histopathology and proteomics demonstrated tumoral enrichment of collagen, proteoglycan, and glycosaminoglycan pathways compared to liver, suggesting matrix remodeling as a key contributor to increased stiffness and viscosity measured by mMRE. The early elevation of SWS and ϕ preceding ADC changes highlights mMRE as a promising tool for detecting tumor-associated biomechanical remodeling and enabling earlier liver cancer diagnosis and monitoring beyond conventional MRI.