Quantifying the Effect of Sex and Neuroanatomical Biomechanical Features on Brain Deformation Response in Finite Element Brain Models.

Recent automotive epidemiology studies have concluded that females have significantly higher odds of sustaining a moderate brain injury or concussion than males in a frontal crash after controlling for multiple crash and occupant variables. Differences in neuroanatomical features, such as intracranial volume (ICV), have been shown between male and female subjects, but how these sex-specific neuroanatomical differences affect brain deformation is unknown. This study used subject-specific finite element brain models, generated via registration-based morphing using both male and female magnetic resonance imaging scans, to investigate sex differences of a variety of neuroanatomical features and their effect on brain deformation; additionally, this study aimed to determine the relative importance of these neuroanatomical features and sex on brain deformation metrics for a single automotive loading environment. Based on the Bayesian linear mixed models, sex had a significant effect on ICV, white matter volume and gray matter volume, as well as a section of cortical gray matter regions' thicknesses and volumes; however, after these neuroanatomical features were accounted for in the statistical model, sex was not a significant factor in predicting brain deformation. ICV had the highest relative effect on the brain deformation metrics assessed. Therefore, ICV should be considered when investigating both brain injury biomechanics and injury risk.

The Effect of Muscle Activation on Head Kinematics During Non-injurious Head Impacts in Human Subjects.

In this study, twenty volunteers were subjected to three, non-injurious lateral head impacts delivered by a 3.7 kg padded impactor at 2 m/s at varying levels of muscle activation (passive, co-contraction, and unilateral contraction). Electromyography was used to quantify muscle activation conditions, and resulting head kinematics were recorded using a custom-fit instrumented mouthpiece. A multi-modal battery of diagnostic tests (evaluated using neurocognitive, balance, symptomatic, and neuroimaging based assessments) was performed on each subject pre- and post-impact. The passive muscle condition resulted in the largest resultant head linear acceleration (12.1 ± 1.8 g) and angular velocity (7.3 ± 0.5 rad/s). Compared to the passive activation, increasing muscle activation decreased both peak resultant linear acceleration and angular velocity in the co-contracted (12.1 ± 1.5 g, 6.8 ± 0.7 rad/s) case and significantly decreased in the unilateral contraction (10.7 ± 1.7 g, 6.5 ± 0.7 rad/s) case. The duration of angular velocity was decreased with an increase in neck muscle activation. No diagnostic metric showed a statistically or clinically significant alteration between baseline and post-impact assessments, confirming these impacts were non-injurious. This study demonstrated that isometric neck muscle activation prior to impact can reduce resulting head kinematics. This study also provides the data necessary to validate computational models of head impact.

An Image Registration-Based Morphing Technique for Generating Subject-Specific Brain Finite Element Models.

Finite element (FE) models of the brain are crucial for investigating the mechanisms of traumatic brain injury (TBI). However, FE brain models are often limited to a single neuroanatomy because the manual development of subject-specific models is time consuming. The objective of this study was to develop a pipeline to automatically generate subject-specific FE brain models using previously developed nonlinear image registration techniques, preserving both external and internal neuroanatomical characteristics. To verify the morphing-induced mesh distortions did not influence the brain deformation response, strain distributions predicted using the morphed model were compared to those from manually created voxel models of the same subject. Morphed and voxel models were generated for 44 subjects ranging in age, and simulated using head kinematics from a football concussion case. For each subject, brain strain distributions predicted by each model type were consistent, and differences in strain prediction was less than 4% between model type. This automated technique, taking approximately 2 h to generate a subject-specific model, will facilitate interdisciplinary research between the biomechanics and neuroimaging fields and could enable future use of biomechanical models in the clinical setting as a tool for improving diagnosis.

Test-retest reliability and long-term stability of three-tissue constrained spherical deconvolution methods for analyzing diffusion MRI data.

PURPOSE: Several recent studies have used a three-tissue constrained spherical deconvolution pipeline to obtain quantitative metrics of brain tissue microstructure from diffusion-weighted MRI data. The three tissue compartments, consisting of white matter, gray matter, and CSF-like (free water) signals, are potentially useful in the evaluation of brain microstructure in a range of pathologies. However, the reliability and long-term stability of these metrics have not yet been evaluated. METHODS: This study examined estimates of whole-brain microstructure for the three tissue compartments, in three separate test-retest cohorts. Each cohort had different lengths of time between baseline and retest, ranging from within the same scanning session in the shortest interval to 3 months in the longest interval. Each cohort was also collected with different acquisition parameters. RESULTS: The CSF-like compartment displayed the greatest reliability across all cohorts, with intraclass correlation coefficient (ICC) values being above 0.95 in each cohort. White matter-like and gray matter-like compartments both demonstrated very high reliability in the immediate cohort (both ICC > 0.90); however, this declined in the 3-month interval cohort to both compartments having ICC > 0.80. Regional CSF-like signal fraction was examined in bilateral hippocampus and had an ICC > 0.80 in each cohort. CONCLUSION: The three-tissue constrained spherical deconvolution techniques provide reliable and stable estimates of tissue-microstructure composition, up to 3 months longitudinally in a control population. This forms an important basis for further investigations using three-tissue constrained spherical deconvolution techniques to track changes in microstructure across a variety of brain pathologies.

Biomechanics of the Human Brain during Dynamic Rotation of the Head.

Traumatic brain injuries (TBI) are a substantial societal burden. The development of better technologies and systems to prevent and/or mitigate the severity of brain injury requires an improved understanding of the mechanisms of brain injury, and more specifically, how head impact exposure relates to brain deformation. Biomechanical investigations have used computational models to identify these relations, but more experimental brain deformation data are needed to validate these models and support their conclusions. The objective of this study was to generate a dataset describing in situ human brain motion under rotational loading at impact conditions considered injurious. Six head-neck human post-mortem specimens, unembalmed and never frozen, were instrumented with 24 sonomicrometry crystals embedded throughout the parenchyma that can directly measure dynamic brain motion. Dynamic brain displacement, relative to the skull, was measured for each specimen with four loading severities in the three directions of controlled rotation, for a total of 12 tests per specimen. All testing was completed 42-72 h post-mortem for each specimen. The final dataset contains approximately 5,000 individual point displacement time-histories that can be used to validate computational brain models. Brain motion was direction-dependent, with axial rotation resulting in the largest magnitude of displacement. Displacements were largest in the mid-cerebrum, and the inferior regions of the brain-the cerebellum and brainstem-experienced relatively lower peak displacements. Brain motion was also found to be positively correlated to peak angular velocity, and negatively correlated with angular velocity duration, a finding that has implications related to brain injury risk-assessment methods. This dataset of dynamic human brain motion will form the foundation for the continued development and refinement of computational models of the human brain for predicting TBI.