Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

Abstract

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

High-frequency microrheology in 3D reveals mismatch between cytoskeletal and extracellular matrix mechanics

“…Importantly, interpreting how mechanical phenotype relates to malignancy depends on the length scale at which the measurement is performed. For example, increased ECM deposition and polymer cross-linking concomitant with malignant transformation manifest increased bulk tissue stiffness as observed in macroscale measurements (21,(26)(27)(28)(29). In contrast, in vitro and ex vivo studies indicate individual cancer cells (microscale) are softer than their normal counterparts, a trait that is thought to be required for dissemination from the primary organ (30,31).…”

Mechanical Characterization by Mesoscale Indentation: Advantages and Pitfalls for Tissue and Scaffolds

“…1). [12][13][14] The cantilever-based probe is displaced vertically into the sample using a software-controlled, position-encoded piezoelectric stage (P-628.1CD; Physik Instrumente). The spherical indentation probe is brought into contact with the tissue sample following a time-dependent displacement profile set by the user in custom LabVIEW code.…”

“…7), rat myocardium, 12 and human tumors. 13,14 The concept of such an infinite, equilibrium, or aggregate modulus is widely applied to viscoelastic and poroelastic materials and models. The reader is directed to the reviews by Chen et al 17 yields similar effective modulus values to that of quasistatic loading (low strain rate; Supplementary Fig.…”

“…In this study, we explore the applicability of indentation at this mesoscale to hydrated, soft matter samples. We and others have developed custom equipment capable of performing indentations at the mesoscale, [7][8][9][10][11][12][13][14] but translating force-displacement data derived from indentation into intrinsic mechanical properties remains a contentious process. As many have argued, Hertz contact models originally developed to derive an elastic modulus from indentation data on hard, elastic materials are inadequate to quantify intrinsic mechanical properties for soft matter.…”

Viscoelastic mapping of mouse brain tissue: relation to structure and age

“…On a tissue scale, there is growing evidence that changes in brain tissue architecture that occurs during neuropathophysiological processes, development, or physiological aging affect the mechanical properties of the brain and thus the local mechanical environment of neurons and glia. To mention a few, reduction of shear modulus was observed during * Corresponding author neuroinflammation [7], Alzheimer's disease [8,9], multiple sclerosis [10,11,12], glial scaring [13] and cancer [14,15].…”