Rate- and Region-Dependent Mechanical Properties of Göttingen Minipig Brain Tissue in Simple Shear and Unconfined Compression.

Traumatic brain injury (TBI), particularly from explosive blasts, is a major cause of casualties in modern military conflicts. Computational models are an important tool in understanding the underlying biomechanics of TBI but are highly dependent on the mechanical properties of soft tissue to produce accurate results. Reported material properties of brain tissue can vary by several orders of magnitude between studies, and no published set of material parameters exists for porcine brain tissue at strain rates relevant to blast. In this work, brain tissue from the brainstem, cerebellum, and cerebrum of freshly euthanized adolescent male Göttingen minipigs was tested in simple shear and unconfined compression at strain rates ranging from quasi-static (QS) to 300 s-1. Brain tissue showed significant strain rate stiffening in both shear and compression. Minimal differences were seen between different regions of the brain. Both hyperelastic and hyper-viscoelastic constitutive models were fit to experimental stress, considering data from either a single loading mode (unidirectional) or two loading modes together (bidirectional). The unidirectional hyper-viscoelastic models with an Ogden hyperelastic representation and a one-term Prony series best captured the response of brain tissue in all regions and rates. The bidirectional models were generally able to capture the response of the tissue in high-rate shear and all compression modes, but not the QS shear. Our constitutive models describe the first set of material parameters for porcine brain tissue relevant to loading modes and rates seen in blast injury.

A Strain Rate-Dependent Constitutive Model for Göttingen Minipig Cerebral Arteries.

Computational simulations of traumatic brain injury (TBI) are commonly used to advance understanding of the injury-pathology relationship, tissue damage thresholds, and design of protective equipment such as helmets. Both human and animal TBI models have developed substantially over recent decades, partially due to the inclusion of more detailed brain geometry and representation of tissues like cerebral blood vessels. Explicit incorporation of vessels dramatically affects local strain and enables researchers to investigate TBI-induced damage to the vasculature. While some studies have indicated that cerebral arteries are rate-dependent, no published experimentally based, rate-sensitive constitutive models of cerebral arteries exist. In this work, we characterize the mechanical properties of axially failed porcine arteries, both quasi-statically (0.01 s-1) and at high rate (>100 s-1), and propose a rate-sensitive model to fit the data. We find that the quasi-static and high-rate stress-stretch curves become significantly different (p < 0.05) above a stretch of 1.23. We additionally find a significant change in both failure stretch and stress as a result of strain rate. The stress-stretch curve is then modeled as a Holzapfel-Gasser-Ogden material, with a Prony series added to capture the effects of viscoelasticity. Ultimately, this paper demonstrates that rate dependence should be considered in the material properties of cerebral arteries undergoing high strain-rate deformations and provides a ready-to-use model for finite element implementation.

Region specific anisotropy and rate dependence of Göttingen minipig brain tissue.

Traumatic brain injury is a major cause of morbidity in civilian as well as military populations. Computational simulations of injurious events are an important tool to understanding the biomechanics of brain injury and evaluating injury criteria and safety measures. However, these computational models are highly dependent on the material parameters used to represent the brain tissue. Reported material properties of tissue from the cerebrum and cerebellum remain poorly defined at high rates and with respect to anisotropy. In this work, brain tissue from the cerebrum and cerebellum of male Göttingen minipigs was tested in one of three directions relative to axon fibers in oscillatory simple shear over a large range of strain rates from 0.025 to 250 s-1. Brain tissue showed significant direction dependence in both regions, each with a single preferred loading direction. The tissue also showed strong rate dependence over the full range of rates considered. Transversely isotropic hyper-viscoelastic constitutive models were fit to experimental data using dynamic inverse finite element models to account for wave propagation observed at high strain rates. The fit constitutive models predicted the response in all directions well at rates below 100 s-1, after which they adequately predicted the initial two loading cycles, with the exception of the 250 s-1 rate, where models performed poorly. These constitutive models can be readily implemented in finite element packages and are suitable for simulation of both conventional and blast injury in porcine, especially Göttingen minipig, models.

Strain-induced collagen denaturation is rate dependent in failure of cerebral arteries.

While soft tissues are commonly damaged by mechanical loading, the manifestation of this damage at the microstructural level is not fully understood. Specifically, while rate-induced stiffening has been previously observed in cerebral arteries, associated changes in microstructural damage patterns following high-rate loading are largely undefined. In this study, we stretched porcine middle cerebral arteries to failure at 0.01 and >150 s-1, both axially and circumferentially, followed by probing for denatured tropocollagen using collagen hybridizing peptide (CHP). We found that collagen fibrils aligned with the loading direction experienced less denaturation following failure tests at high than low rates. Others have demonstrated similar rate dependence in tropocollagen denaturation during soft tissue failure, but this is the first study to quantify this behavior using CHP and to report it for cerebral arteries. These findings may have significant implications for traumatic brain injury and intracranial balloon angioplasty. We additionally observed possible tropocollagen denaturation in vessel layers primarily composed of fibrils transversely aligned to the loading axis. To our knowledge, this is the first observation of collagen denaturation due to transverse loading, but further research is needed to confirm this finding. STATEMENT OF SIGNIFICANCE: Previous work shows that collagen hybridizing peptide (CHP) can be used to identify collagen molecule unfolding and denaturation in mechanically overloaded soft tissues, including the cerebral arteries. But experiments have not explored collagen damage at rates relevant to traumatic brain injury. In this work, we quantified collagen damage in cerebral arteries stretched to failure at both high and low rates. We found that the collagen molecule is less damaged at high than at low rates, suggesting that damage mechanisms of either the collagen molecule or other elements of the collagen superstructure are rate dependent. This work implies that arteries failed at high rates, such as in traumatic brain injury, will have different molecular-level damage patterns than arteries failed at low rates. Consequently, improved understanding of damage characteristics may be expanded in the future to better inform clinically relevant cases of collagen damage such as angioplasty and injury healing.

A 3-D Finite-Element Minipig Model to Assess Brain Biomechanical Responses to Blast Exposure.

Despite years of research, it is still unknown whether the interaction of explosion-induced blast waves with the head causes injury to the human brain. One way to fill this gap is to use animal models to establish "scaling laws" that project observed brain injuries in animals to humans. This requires laboratory experiments and high-fidelity mathematical models of the animal head to establish correlates between experimentally observed blast-induced brain injuries and model-predicted biomechanical responses. To this end, we performed laboratory experiments on Göttingen minipigs to develop and validate a three-dimensional (3-D) high-fidelity finite-element (FE) model of the minipig head. First, we performed laboratory experiments on Göttingen minipigs to obtain the geometry of the cerebral vasculature network and to characterize brain-tissue and vasculature material properties in response to high strain rates typical of blast exposures. Next, we used the detailed cerebral vasculature information and species-specific brain tissue and vasculature material properties to develop the 3-D high-fidelity FE model of the minipig head. Then, to validate the model predictions, we performed laboratory shock-tube experiments, where we exposed Göttingen minipigs to a blast overpressure of 210 kPa in a laboratory shock tube and compared brain pressures at two locations. We observed a good agreement between the model-predicted pressures and the experimental measurements, with differences in maximum pressure of less than 6%. Finally, to evaluate the influence of the cerebral vascular network on the biomechanical predictions, we performed simulations where we compared results of FE models with and without the vasculature. As expected, incorporation of the vasculature decreased brain strain but did not affect the predictions of brain pressure. However, we observed that inclusion of the cerebral vasculature in the model changed the strain distribution by as much as 100% in regions near the interface between the vasculature and the brain tissue, suggesting that the vasculature does not merely decrease the strain but causes drastic redistributions. This work will help establish correlates between observed brain injuries and predicted biomechanical responses in minipigs and facilitate the creation of scaling laws to infer potential injuries in the human brain due to exposure to blast waves.