Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology

Simple Summary Biomechanics has emerged as a key player in diffuse glioma progression and invasion, as the glioma cells interact both chemically and mechanically with the extracellular matrix to facilitate proliferation and cell migration, altering the mechanical properties of tumor and adjacent brain tissue. The quantification of these properties is expected to contribute to advances in glioma biology, diagnostic instrumentation, and treatment technology. Previous studies have associated isocitrate dehydrogenase gene family (IDH) mutations and World Health Organization (WHO) grade with differences in glioma elasticity, although not on fresh tissue specimens. This is the first study to investigate the combined influence of glioma IDH mutation status and WHO grade on both tumor and peritumoral white matter fresh tissue elasticity by using atomic force microscope (AFM) nanoindentation. It is also the first to systematically determine the elastic modulus of human white matter using AFM nanoindentation with spherical tips on fresh tissue slices ex vivo. This study aims to investigate the influence of isocitrate dehydrogenase gene family (IDH) mutations, World Health Organization (WHO) grade, and mechanical preconditioning on glioma and adjacent brain elasticity through standard monotonic and repetitive atomic force microscope (AFM) nanoindentation. The elastic modulus was measured ex vivo on fresh tissue specimens acquired during craniotomy from the tumor and the peritumoral white matter of 16 diffuse glioma patients. Linear mixed-effects models examined the impact of tumor traits and preconditioning on tissue elasticity. Tissues from IDH-mutant cases were stiffer than those from IDH-wildtype ones among anaplastic astrocytoma patients (p = 0.0496) but of similar elasticity to IDH-wildtype cases for diffuse astrocytoma patients (p = 0.480). The tumor was found to be non-significantly softer than white matter in anaplastic astrocytomas (p = 0.070), but of similar elasticity to adjacent brain in diffuse astrocytomas (p = 0.492) and glioblastomas (p = 0.593). During repetitive indentation, both tumor (p = 0.002) and white matter (p = 0.003) showed initial stiffening followed by softening. Stiffening was fully reversed in white matter (p = 0.942) and partially reversed in tumor (p = 0.015). Tissue elasticity comprises a phenotypic characteristic closely related to glioma histopathology. Heterogeneity between patients should be further explored.

Automated summary

Biomechanics plays a key role in diffuse glioma progression, with glioma cells interacting chemically and mechanically with the extracellular matrix to affect proliferation and migration. Isocitrate dehydrogenase gene family mutations and WHO grade impact glioma elasticity, and AFM nanoindentation helps measure tissue elasticity. Different glioma types show varying responses in terms of tissue elasticity, indicating further research is needed to understand patient heterogeneity.