Cavitation induced fracture of intact brain tissue

Abstract

Nonpenetrating traumatic brain injuries (TBIs) are linked to cavitation. The structural organization of the brain makes it particularly susceptible to tears and fractures from these cavitation events, but limitations in existing characterization methods make it difficult to understand the relationship between fracture and cavitation in this tissue. More broadly, fracture energy is an important, yet often overlooked, mechanical property of all soft tissues. We combined needle-induced cavitation with hydraulic fracture models to induce and quantify fracture in intact brains at precise locations. We report here the first measurements of the fracture energy of intact brain tissue that range from 1.5 to 8.9 J/m², depending on the location in the brain and the model applied. We observed that fracture consistently occurs along interfaces between regions of brain tissue. These fractures along interfaces allow cavitation-related damage to propagate several millimeters away from the initial injury site. Quantifying the forces necessary to fracture brain and other soft tissues is critical for understanding how impact and blast waves damage tissue in vivo and has implications for the design of protective gear and tissue engineering.

Figure 1

Intact brain fracture energy using NIC. (a) Three observed pressure-time trends (1, pink; 2, teal, and 3, black) in experimental data have different slopes after a maximum pressure is reached. Burst shape indicates the timepoint for the critical event and blue dashed line indicates when the syringe pump is turned off. (b) Log-log data transformation from (a) between the maximum pressure value to when the pump was turned off. Trendlines show slopes of typical trends observed. (c) The distribution of experiments with slopes in the ranges: −0.38 ≤ slope ≤ −0.26 (pink), −0.25 ≤ slope ≤ −0.15 (teal), or −0.15 < slope < −0.38 (black). (d) The fracture energies of mouse brain calculated using the plane strain or axisymmetric hydraulic fracture models. Asterisks in (d) denote p < 0.05, the dashed line represents the mean, the dotted lines represent quartiles, and the violin plot shows the full range of data. To see this figure in color, go online.

Figure 2

Fracture occurs along tissue interface. Through subsequent 100-μm-thick horizontal slices of mouse brain, starting in the top left image (1.8 mm deep) and ending with the bottom right image (2.9 mm deep), fracture occurs along the hippocampus interface (white arrows) in the brain, visible by both DAPI staining (blue) and fluorescent beads (red). The scale bars represent 1 mm. To see this figure in color, go online.

Figure 3

Alginate gel fracture energies in NIC consistent with pure shear. (a) NIC measured moduli for soft and hard alginate gels (p < 0.0001). (b) Front and side views of NIC-induced fracture in a hard alginate gel. (c) Picture of pure shear testing of a hard alginate gel. Fracture energy of the (d) soft and (e) hard alginate gels measured by NIC and pure shear testing. For NIC experiments the values were calculated using either the plane strain (pink) or axisymmetric (teal) model. Scale bars represent 2 cm, and solid lines represent means of data sets. To see this figure in color, go online.

Figure 4

Numerical simulations of hydraulic fracture in brain tissue. (a) Cohesive traction-separation law is applied to study fracture in brain tissue. (b) A schematic of NIC-induced fracture. (c) Stress distribution of finite element simulations for the plane strain case. (d) The pressure-time curves for varying material properties for the plane strain case. (e) The slope of pressure-time curves with varied material properties for the plane strain case. (f) Stress distribution of finite element simulations for the axisymmetric case. (g) The pressure-time curves for varying material properties for the axisymmetric case. (h) The slope of pressure-time curves with varied material properties for the axisymmetric case. Dashed lines in (d and g) are the results of FE simulations, and solid lines are the results from theoretical analysis. To see this figure in color, go online.