Localized characterization of brain tissue mechanical properties by needle induced cavitation rheology and volume controlled cavity expansion.

Changes in the elastic properties of brain tissue have been correlated with injury, cancers, and neurodegenerative diseases. However, discrepancies in the reported elastic moduli of brain tissue are persistent, and spatial inhomogeneities complicate the interpretation of macroscale measurements such as rheology. Here we introduce needle induced cavitation rheology (NICR) and volume-controlled cavity expansion (VCCE) as facile methods to measure the apparent Young's modulus E of minimally manipulated brain tissue, at specific tissue locations and with sub-millimeter spatial resolution. For different porcine brain regions and sections analyzed by NICR, we found E to be 3.7 ± 0.7 kPa and 4.8 ± 1.0 kPa for gray matter, and white matter, respectively. For different porcine brain regions and sections analyzed by VCCE, we found E was 0.76 ± 0.02 kPa for gray matter and 0.92 ± 0.01 kPa for white matter. Measurements from VCCE were more similar to those obtained from macroscale shear rheology (0.75 ± 0.06 kPa) and from instrumented microindentation of white matter (0.97 ± 0.40 kPa) and gray matter (0.86 ± 0.20 kPa). We attributed the higher stiffness reported from NICR to that method's assumption of a cavitation instability due to a neo-Hookean constitutive response, which does not capture the strain-stiffening behavior of brain tissue under large strains, and therefore did not provide appropriate measurements. We demonstrate via both analytical modeling of a spherical cavity and finite element modeling of a needle geometry, that this strain stiffening may prevent a cavitation instability. VCCE measurements take this stiffening behavior into account by employing an incompressible one-term Ogden model to find the nonlinear elastic properties of the tissue. Overall, VCCE afforded rapid and facile measurement of nonlinear mechanical properties of intact, healthy mammalian brain tissue, enabling quantitative comparison among brain tissue regions and also between species. Finally, accurate estimation of elastic properties for this strain stiffening tissue requires methods that include appropriate constitutive models of the brain tissue response, which here are represented by inclusion of the Ogden model in VCCE.

The intimate relationship between cavitation and fracture.

Nearly three decades ago, the field of mechanics was cautioned of the obscure nature of cavitation processes in soft materials [A. Gent, Cavitation in rubber: a cautionary tale, Rubber Chem. Technol., 1990, 63, 49-53]. Since then, the debate on the mechanisms that drive this failure process is ongoing. Using a high precision volume controlled cavity expansion procedure, this paper reveals the intimate relationship between cavitation and fracture. Combining a Griffith inspired formulation for crack propagation, and a Gent inspired formulation for cavity expansion, we show that despite the apparent complexity of the fracture patterns, the pressure-volume response follows a predictable path. In contrast to available studies, both the model and our experiments are able to track the entire process including the unstable branch, by controlling the volume of the cavity. Moreover, this minimal theoretical framework is able to explain the ambiguity in previous experiments by revealing the presence of metastable states that can lead to first order transitions at onset of fracture. The agreement between the simple theory and all of the experimental results conducted in PDMS samples with shear moduli in the range of 25-246 [kPa] confirms that cavitation and fracture work together in driving the expansion process. Through this study we also determine the fracture energy of PDMS and show its significant dependence on strain stiffening.

Volume-controlled cavity expansion for probing of local elastic properties in soft materials.

Cavity expansion can be used to measure the local nonlinear elastic properties in soft materials, regardless of the specific damage or instability mechanism that it may ultimately induce. To that end, we introduce a volume-controlled cavity expansion procedure and an accompanying method that builds on the Cavitation Rheology technique [J. A. Zimberlin et al., Soft Matter, 2007, 3, 763-767], but without relying on the maximum recorded pressure. This is achieved by determining an effective radius of the cavity that is based on the volume measurements, and is further supported by numerical simulations. Applying this method to PDMS samples, we show that it consistently collapses the experimental curves to the theoretical prediction of cavity expansion prior to the occurrence of fracture or cavitation, thus resulting in high precision measurement with less than 5% of scatter and good agreement with results obtained via conventional techniques. Moreover, since it does not require visual tracking of the cavity, this technique can be applied to measure the nonlinear elastic response in opaque samples.