Non-invasive measurements of tumor mechanical forces using fiber Bragg grating sensors

Mechanical forces in solid tumors strongly affect tumor progression, invasion and treatment. Over the years, several approaches have been developed to investigate tumor mechanobiology, however, existing techniques to quantify mechanical forces remain invasive and rely on indirect estimations of mechanical stress through mathematical modeling and entailing several assumptions. To address these challenges, we introduced a non-invasive method for in vivo measurement of macroscopic mechanical forces in solid tumors and the surrounding normal tissue. The proposed approach relies on a multi-sensor tactile imaging system based on fiber Bragg grating sensors (FBGs) to measure tumor forces and reconstruct 2D spatial force distributions. Unlike existing methods, this technique does not require the use of mathematical modeling, providing a clinically translatable framework for longitudinal monitoring of tumor mechanics. The method was applied to orthotopic 4T1 and E0771 murine breast tumor models at four time points during progression. The results demonstrated the capability of this technique to quantify the magnitude of forces in both tumor and surrounding normal tissue, allowing the reconstruction of spatial distributions that reflect the heterogeneous mechanical responses across the investigated area. Higher force levels were detected at tumor sites, and their temporal evolution was correlated with tumor volume and stiffness. The corresponding stress values were consistent with previous computational predictions, providing in vivo evidence of solid-stress accumulation in growing tumors. Overall, this study offers a complementary and directly translated to humans' strategy, expanding the experimental tools available for investigating tumor mechanics. STATEMENT OF SIGNIFICANCE: Tumor mechanical forces strongly affect tumor progression, invasion, and drug delivery. However, current approaches for quantifying these forces remain invasive and rely on indirect estimations through mathematical modeling. To address these limitations, we propose a method for the direct, non-invasive, in vivo measurement of tumor mechanical forces using fiber Bragg grating sensors. The method was assessed in orthotopic 4T1 and E0771 murine breast tumor models. Two-dimensional force maps revealed heterogeneous mechanical responses across tumor and surrounding normal tissue. Higher forces were detected at tumor sites and correlated with tumor volume and stiffness. This study provides a clinically translatable strategy that expands the experimental tools available for investigating tumor mechanics, with potential implications for cancer diagnosis, treatment, and therapy monitoring.