Effect of Human Head Shape on the Risk of Traumatic Brain Injury: A Gaussian Process Regression-based Machine Learning Approach.

INTRODUCTION: Computational head injury models are promising tools for understanding and predicting traumatic brain injuries. However, most available head injury models are "average" models that employ a single set of head geometry (e.g., 50th-percentile U.S. male) without considering variability in these parameters across the human population. A significant variability of head shapes exists in U.S. Army soldiers, evident from the Anthropometric Survey of U.S. Army Personnel (ANSUR II). The objective of this study is to elucidate the effects of head shape on the predicted risk of traumatic brain injury from computational head injury models. MATERIALS AND METHODS: Magnetic resonance imaging scans of 25 human subjects are collected. These images are registered to the standard MNI152 brain atlas, and the resulting transformation matrix components (called head shape parameters) are used to quantify head shapes of the subjects. A generative machine learning model is used to generate 25 additional head shape parameter datasets to augment our database. Head injury models are developed for these head shapes, and a rapid injurious head rotation event is simulated to obtain several brain injury predictor variables (BIPVs): Peak cumulative maximum principal strain (CMPS), average CMPS, and the volume fraction of brain exceeding an injurious CMPS threshold. A Gaussian process regression model is trained between head shape parameters and BIPVs, which is then used to study the relative sensitivity of the various BIPVs on individual head shape parameters. We distinguish head shape parameters into 2 types: Scaling components ${T_{xx}}$, ${T_{yy}}$, and ${T_{zz}}$ that capture the breadth, length, and height of the head, respectively, and shearing components (${T_{xy}},{T_{xz}},{T_{yx}},{T_{yz}},{T_{zx}}$, and ${T_{zy}}$) that capture the relative skewness of the head shape. RESULTS: An overall positive correlation is evident between scaling components and BIPVs. Notably, a very high, positive correlation is seen between the BIPVs and the head volume. As an example, a 57% increase in peak CMPS was noted between the smallest and the largest investigated head volume parameters. The variation in shearing components ${T_{xy}},{T_{xz}},{T_{yx}},{T_{yz}},{T_{zx}}$, and ${T_{zy}}$ on average does not cause notable changes in the BIPVs. From the Gaussian process regression model, all 3 BIPVs showed an increasing trend with each of the 3 scaling components, but the BIPVs are found to be most sensitive to the height dimension of the head. From the Sobol sensitivity analysis, the ${T_{zz}}$ scaling parameter contributes nearly 60% to the total variance in peak and average CMPS; ${T_{yy}}$ contributes approximately 20%, whereas ${T_{xx}}$ contributes less than 5%. The remaining contribution is from the 6 shearing components. Unlike peak and average CMPS, the VF-CMPS BIPV is associated with relatively evenly distributed Sobol indices across the 3 scaling parameters. Furthermore, the contribution of shearing components on the total variance in this case is negligible. CONCLUSIONS: Head shape has a considerable influence on the injury predictions of computational head injury models. Available "average" head injury models based on a 50th-percentile U.S. male are likely associated with considerable uncertainty. In general, larger head sizes correspond to greater BIPV magnitudes, which point to potentially a greater injury risk under rapid neck rotation for people with larger heads.

Comparison of Deformation Patterns Excited in the Human Brain In Vivo by Harmonic and Impulsive Skull Motion.

Noninvasive measurements of brain deformation in human participants in vivo are needed to develop models of brain biomechanics and understand traumatic brain injury (TBI). Tagged magnetic resonance imaging (tagged MRI) and magnetic resonance elastography (MRE) are two techniques to study human brain deformation; these techniques differ in the type of motion and difficulty of implementation. In this study, oscillatory strain fields in the human brain caused by impulsive head acceleration and measured by tagged MRI were compared quantitatively to strain fields measured by MRE during harmonic head motion at 10 and 50 Hz. Strain fields were compared by registering to a common anatomical template, then computing correlations between the registered strain fields. Correlations were computed between tagged MRI strain fields in six participants and MRE strain fields at 10 Hz and 50 Hz in six different participants. Correlations among strain fields within the same experiment type were compared statistically to correlations from different experiment types. Strain fields from harmonic head motion at 10 Hz imaged by MRE were qualitatively and quantitatively similar to modes excited by impulsive head motion, imaged by tagged MRI. Notably, correlations between strain fields from 10 Hz MRE and tagged MRI did not differ significantly from correlations between strain fields from tagged MRI. These results suggest that low-frequency modes of oscillation dominate the response of the brain during impact. Thus, low-frequency MRE, which is simpler and more widely available than tagged MRI, can be used to illuminate the brain's response to head impact.

Characterization of material properties and deformation in the ANGUS phantom during mild head impacts using MRI.

Traumatic brain injury (TBI) is a major health concern affecting both military and civilian populations. Despite notable advances in TBI research in recent years, there remains a significant gap in linking the impulsive loadings from a blast or a blunt impact to the clinical injury patterns observed in TBI. Synthetic head models or phantoms can be used to establish this link as they can be constructed with geometry, anatomy, and material properties that match the human brain, and can be used as an alternative to animal models. This study presents one such phantom called the Anthropomorphic Neurologic Gyrencephalic Unified Standard (ANGUS) phantom, which is an idealized gyrencephalic brain phantom composed of polyacrylamide gel. Here we mechanically characterized the ANGUS phantom using tagged magnetic resonance imaging (MRI) and magnetic resonance elastography (MRE), and then compared the outcomes to data obtained in healthy volunteers. The direct comparison between the phantom's response and the data from a cohort of in vivo human subjects demonstrate that the ANGUS phantom may be an appropriate model for bulk tissue response and gyral dynamics of the human brain under small amplitude linear impulses. However, the phantom's response differs from that of the in vivo human brain under rotational impacts, suggesting avenues for future improvements to the phantom.

Data-driven Uncertainty Quantification in Computational Human Head Models.

Computational models of the human head are promising tools for estimating the impact-induced response of the brain, and thus play an important role in the prediction of traumatic brain injury. The basic constituents of these models (i.e., model geometry, material properties, and boundary conditions) are often associated with significant uncertainty and variability. As a result, uncertainty quantification (UQ), which involves quantification of the effect of this uncertainty and variability on the simulated response, becomes critical to ensure reliability of model predictions. Modern biofidelic head model simulations are associated with very high computational cost and high-dimensional inputs and outputs, which limits the applicability of traditional UQ methods on these systems. In this study, a two-stage, data-driven manifold learning-based framework is proposed for UQ of computational head models. This framework is demonstrated on a 2D subject-specific head model, where the goal is to quantify uncertainty in the simulated strain fields (i.e., output), given variability in the material properties of different brain substructures (i.e., input). In the first stage, a data-driven method based on multi-dimensional Gaussian kernel-density estimation and diffusion maps is used to generate realizations of the input random vector directly from the available data. Computational simulations of a small number of realizations provide input-output pairs for training data-driven surrogate models in the second stage. The surrogate models employ nonlinear dimensionality reduction using Grassmannian diffusion maps, Gaussian process regression to create a low-cost mapping between the input random vector and the reduced solution space, and geometric harmonics models for mapping between the reduced space and the Grassmann manifold. It is demonstrated that the surrogate models provide highly accurate approximations of the computational model while significantly reducing the computational cost. Monte Carlo simulations of the surrogate models are used for uncertainty propagation. UQ of the strain fields highlights significant spatial variation in model uncertainty, and reveals key differences in uncertainty among commonly used strain-based brain injury predictor variables.

MR Imaging of Human Brain Mechanics In Vivo: New Measurements to Facilitate the Development of Computational Models of Brain Injury.

Computational models of the brain and its biomechanical response to skull accelerations are important tools for understanding and predicting traumatic brain injuries (TBIs). However, most models have been developed using experimental data collected on animal models and cadaveric specimens, both of which differ from the living human brain. Here we describe efforts to noninvasively measure the biomechanical response of the human brain with MRI-at non-injurious strain levels-and generate data that can be used to develop, calibrate, and evaluate computational brain biomechanics models. Specifically, this paper reports on a project supported by the National Institute of Neurological Disorders and Stroke to comprehensively image brain anatomy and geometry, mechanical properties, and brain deformations that arise from impulsive and harmonic skull loadings. The outcome of this work will be a publicly available dataset ( http://www.nitrc.org/projects/bbir ) that includes measurements on both males and females across an age range from adolescence to older adulthood. This article describes the rationale and approach for this study, the data available, and how these data may be used to develop new computational models and augment existing approaches; it will serve as a reference to researchers interested in using these data.

Group characterization of impact-induced, in vivo human brain kinematics.

Brain movement during an impact can elicit a traumatic brain injury, but tissue kinematics vary from person to person and knowledge regarding this variability is limited. This study examines spatio-temporal brain-skull displacement and brain tissue deformation across groups of subjects during a mild impact in vivo. The heads of two groups of participants were imaged while subjected to a mild (less than 350 rad s-2) impact during neck extension (NE, n = 10) and neck rotation (NR, n = 9). A kinematic atlas of displacement and strain fields averaged across all participants was constructed and compared against individual participant data. The atlas-derived mean displacement magnitude was 0.26 ± 0.13 mm for NE and 0.40 ± 0.26 mm for NR, which is comparable to the displacement magnitudes from individual participants. The strain tensor from the atlas displacement field exhibited maximum shear strain (MSS) of 0.011 ± 0.006 for NE and 0.017 ± 0.009 for NR and was lower than the individual MSS averaged across participants. The atlas illustrates common patterns, containing some blurring but visible relationships between anatomy and kinematics. Conversely, the direction of the impact, brain size, and fluid motion appear to underlie kinematic variability. These findings demonstrate the biomechanical roles of key anatomical features and illustrate common features of brain response for model evaluation.

Calibration of a Heterogeneous Brain Model Using a Subject-Specific Inverse Finite Element Approach.

Central to the investigation of the biomechanics of traumatic brain injury (TBI) and the assessment of injury risk from head impact are finite element (FE) models of the human brain. However, many existing FE human brain models have been developed with simplified representations of the parenchyma, which may limit their applicability as an injury prediction tool. Recent advances in neuroimaging techniques and brain biomechanics provide new and necessary experimental data that can improve the biofidelity of FE brain models. In this study, the CAB-20MSym template model was developed, calibrated, and extensively verified. To implement material heterogeneity, a magnetic resonance elastography (MRE) template image was leveraged to define the relative stiffness gradient of the brain model. A multi-stage inverse FE (iFE) approach was used to calibrate the material parameters that defined the underlying non-linear deviatoric response by minimizing the error between model-predicted brain displacements and experimental displacement data. This process involved calibrating the infinitesimal shear modulus of the material using low-severity, low-deformation impact cases and the material non-linearity using high-severity, high-deformation cases from a dataset of in situ brain displacements obtained from cadaveric specimens. To minimize the geometric discrepancy between the FE models used in the iFE calibration and the cadaveric specimens from which the experimental data were obtained, subject-specific models of these cadaveric brain specimens were developed and used in the calibration process. Finally, the calibrated material parameters were extensively verified using independent brain displacement data from 33 rotational head impacts, spanning multiple loading directions (sagittal, coronal, axial), magnitudes (20-40 rad/s), durations (30-60 ms), and severity. Overall, the heterogeneous CAB-20MSym template model demonstrated good biofidelity with a mean overall CORA score of 0.63 ± 0.06 when compared to in situ brain displacement data. Strains predicted by the calibrated model under non-injurious rotational impacts in human volunteers (N = 6) also demonstrated similar biofidelity compared to in vivo measurements obtained from tagged magnetic resonance imaging studies. In addition to serving as an anatomically accurate model for further investigations of TBI biomechanics, the MRE-based framework for implementing material heterogeneity could serve as a foundation for incorporating subject-specific material properties in future models.

Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures.

Traumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration. SARM1 protein is a central driver of axon degeneration through a conserved molecular pathway. Sarm1-/- mice with knockout (KO) of the Sarm1 gene enable genetic proof-of-concept testing of the SARM1 pathway as a therapeutic target. We evaluated Sarm1 deletion effects after TBI using a concussive model that causes traumatic axonal injury and progresses to CC atrophy at 10 weeks, indicating post-traumatic neurodegeneration. Sarm1 wild-type (WT) mice developed significant CC atrophy that was reduced in Sarm1 KO mice. Ultrastructural classification of pathology of individual axons, using electron microscopy, demonstrated that Sarm1 KO preserved more intact axons and reduced damaged or demyelinated axons. Longitudinal MRI studies in live mice identified significantly reduced CC volume after TBI in Sarm1 WT mice that was attenuated in Sarm1 KO mice. MR diffusion tensor imaging detected reduced fractional anisotropy in both genotypes while axial diffusivity remained higher in Sarm1 KO mice. Immunohistochemistry revealed significant attenuation of CC atrophy, myelin loss, and neuroinflammation in Sarm1 KO mice after TBI. Functionally, Sarm1 KO mice exhibited beneficial effects in motor learning and sleep behavior. Based on these findings, Sarm1 inactivation can protect axons and white matter tracts to improve translational outcomes associated with CC atrophy and post-traumatic neurodegeneration.

Sensitive detection of extremely small iron oxide nanoparticles in living mice using MP2RAGE with advanced image co-registration.

Magnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo. In this study, an optimized Magnetization Prepared-RApid Gradient Echo (MP-RAGE) with 2 inversion times called MP2RAGE combined with advanced image co-registration is presented as an effective non-invasive methodology to quantitatively detect T1 MR contrast agents. The optimized MP2RAGE produced high quality in vivo mouse brain T1 (or R1 = 1/T1) map with high spatial resolution, 160 × 160 × 160 µm3 voxel at 9.4 T. Test-retest signal to noise was > 20 for most voxels. Extremely small iron oxide nanoparticles (ESIONPs) having 3 nm core size and 11 nm hydrodynamic radius after polyethylene glycol (PEG) coating were intracranially injected into mouse brain and detected as a proof-of-concept. Two independent MP2RAGE MR scans were performed pre- and post-injection of ESIONPs followed by advanced image co-registration. The comparison of two T1 (or R1) maps after image co-registration provided precise and quantitative assessment of the effects of the injected ESIONPs at each voxel. The proposed MR protocol has potential for future use in the detection of T1 molecular contrast agents.

Translationally Relevant Magnetic Resonance Imaging Markers in a Ferret Model of Closed Head Injury.

Pre-clinical models of traumatic brain injury (TBI) have been the primary experimental tool for understanding the potential mechanisms and cellular alterations that follow brain injury, but the human relevance and translational value of these models are often called into question. Efforts to better recapitulate injury biomechanics and the use of non-rodent species with neuroanatomical similarities to humans may address these concerns and promise to advance experimental studies toward clinical impact. In addition to improving translational aspects of animal models, it is also advantageous to establish pre-clinical outcomes that can be directly compared with the same outcomes in humans. Non-invasive imaging and particularly MRI is promising for this purpose given that MRI is a primary tool for clinical diagnosis and at the same time increasingly available at the pre-clinical level. The objective of this study was to identify which commonly used radiologic markers of TBI outcomes can be found also in a translationally relevant pre-clinical model of TBI. The ferret was selected as a human relevant species for this study with folded cortical geometry and relatively high white matter content and the closed head injury model of engineered rotation and acceleration (CHIMERA) TBI model was selected for biomechanical similarities to human injury. A comprehensive battery of MRI protocols based on common data elements (CDEs) for human TBI was collected longitudinally for the identification of MRI markers and voxelwise analysis of T2, contrast enhancement and diffusion tensor MRI values. The most prominent MRI findings were consistent with focal hemorrhage and edema in the brain stem region following high severity injury as well as vascular and meningeal injury evident by contrast enhancement. While conventional MRI outcomes were not highly conspicuous in less severe cases, quantitative voxelwise analysis indicated diffusivity and anisotropy alterations in the acute and chronic periods after TBI. The main conclusions of this study support the translational relevance of closed head TBI models in intermediate species and identify brain stem and meningeal vulnerability. Additionally, the MRI findings highlight a subset of CDEs with promise to bridge pre-clinical studies with human TBI outcomes.

Integrating material properties from magnetic resonance elastography into subject-specific computational models for the human brain.

Advances in brain imaging and computational methods have facilitated the creation of subject-specific computational brain models that aid researchers in investigating brain trauma using simulated impacts. The emergence of magnetic resonance elastography (MRE) as a non-invasive mechanical neuroimaging tool has enabled in vivo estimation of material properties at low-strain, harmonic loading. An open question in the field has been how this data can be integrated into computational models. The goals of this study were to use a novel MRI dataset acquired in human volunteers to generate models with subject-specific anatomy and material properties, and then to compare simulated brain deformations to subject-specific brain deformation data under non-injurious loading. Models of five subjects were simulated with linear viscoelastic (LVE) material properties estimated directly from MRE data. Model predictions were compared to experimental brain deformation acquired in the same subjects using tagged MRI. Outcomes from the models matched the spatial distribution and magnitude of the measured peak strain components as well as the 95th percentile in-plane peak strains within 0.005 mm/mm and maximum principal strain within 0.012 mm/mm. Sensitivity to material heterogeneity was also investigated. Simulated brain deformations from a model with homogenous brain properties and a model with brain properties discretized with up to ten regions were very similar (a mean absolute difference less than 0.0015 mm/mm in peak strains). Incorporating material properties directly from MRE into a biofidelic subject-specific model is an important step toward future investigations of higher-order model features and simulations under more severe loading conditions.

Transplantation of induced neural stem cells (iNSCs) into chronically demyelinated corpus callosum ameliorates motor deficits.

Multiple Sclerosis (MS) causes neurologic disability due to inflammation, demyelination, and neurodegeneration. Immunosuppressive treatments can modify the disease course but do not effectively promote remyelination or prevent long term neurodegeneration. As a novel approach to mitigate chronic stage pathology, we tested transplantation of mouse induced neural stem cells (iNSCs) into the chronically demyelinated corpus callosum (CC) in adult mice. Male C57BL/6 mice fed 0.3% cuprizone for 12 weeks exhibited CC atrophy with chronic demyelination, astrogliosis, and microglial activation. Syngeneic iNSCs were transplanted into the CC after ending cuprizone and perfused for neuropathology 2 weeks later. Magnetic resonance imaging (MRI) sequences for magnetization transfer ratio (MTR), diffusion-weighted imaging (T2), and diffusion tensor imaging (DTI) quantified CC pathology in live mice before and after iNSC transplantation. Each MRI technique detected progressive CC pathology. Mice that received iNSCs had normalized DTI radial diffusivity, and reduced astrogliosis post-imaging. A motor skill task that engages the CC is Miss-step wheel running, which demonstrated functional deficits from cuprizone demyelination. Transplantation of iNSCs resulted in marked recovery of running velocity. Neuropathology after wheel running showed that iNSC grafts significantly increased host oligodendrocytes and proliferating oligodendrocyte progenitors, while modulating axon damage. Transplanted iNSCs differentiated along astrocyte and oligodendrocyte lineages, without myelinating, and many remained neural stem cells. Our findings demonstrate the applicability of neuroimaging and functional assessments for pre-clinical interventional trials during chronic demyelination and detect improved function from iNSC transplantation. Directly reprogramming fibroblasts into iNSCs facilitates the future translation towards exogenous autologous cell therapies.

In vivo estimates of axonal stretch and 3D brain deformation during mild head impact.

The rapid deformation of brain tissue in response to head impact can lead to traumatic brain injury. In vivo measurements of brain deformation during non-injurious head impacts are necessary to understand the underlying mechanisms of traumatic brain injury and compare to computational models of brain biomechanics. Using tagged magnetic resonance imaging (MRI), we obtained measurements of three-dimensional strain tensors that resulted from a mild head impact after neck rotation or neck extension. Measurements of maximum principal strain (MPS) peaked shortly after impact, with maximal values of 0.019-0.053 that correlated strongly with peak angular velocity. Subject-specific patterns of MPS were spatially heterogeneous and consistent across subjects for the same motion, though regions of high deformation differed between motions. The largest MPS values were seen in the cortical gray matter and cerebral white matter for neck rotation and the brainstem and cerebellum for neck extension. Axonal fiber strain (Ef) was estimated by combining the strain tensor with diffusion tensor imaging data. As with MPS, patterns of Ef varied spatially within subjects, were similar across subjects within each motion, and showed group differences between motions. Values were highest and most strongly correlated with peak angular velocity in the corpus callosum for neck rotation and in the brainstem for neck extension. The different patterns of brain deformation between head motions highlight potential areas of greater risk of injury between motions at higher loading conditions. Additionally, these experimental measurements can be directly compared to predictions of generic or subject-specific computational models of traumatic brain injury.

Quantitative Validation of MRI-Based Motion Estimation for Brain Impact Biomechanics.

Head impact can cause traumatic brain injury (TBI) through axonal overstretch or subsequent inflammation and understanding the biomechanics of the impact event is useful for TBI prevention research. Tagged magnetic resonance imaging (MRI) acquired during a mild-acceleration impact has enabled measurement and visualization of brain deformation in vivo. However, measurements using MRI are subject to error, and having independent validation while imaging in vivo is very difficult. Thus, characterizing the accuracy of these measurements needs to be done in a separate experiment using a phantom where a gold standard is available. This study describes a method for error quantification using a calibration phantom compatible with MRI and high-speed video (the gold standard). During linear acceleration, the maximum shear strain (MSS) in the phantom ranged from 0 to 12%, which is similar to in vivo brain deformation at a similar acceleration. The mean displacement error against video was 0.3±0.3 mm, and the MSS error was 1.4±0.3%. To match resolutions, video data was filtered temporally using an averaging filter. Compared to the unfiltered results, resolution matching improved the agreement between MRI and video results by 15%. In conclusion, tagged MRI analysis compares well to video data provided that resolutions are matched-a finding that is also applicable when using MRI to validate simulations.

Mild traumatic brain injury induced by primary blast overpressure produces dynamic regional changes in [18F]FDG uptake.

Changes in 18F-fluorodeoxyglucose ([18F]FDG) measured by positron emission tomography (PET) can be used for the noninvasive detection of metabolic dysfunction following mild traumatic brain injury (mTBI). This study examined the time course of metabolic changes induced by primary blast injury by measuring regional [18F]FDG uptake. Adult, male rats were exposed to blast overpressure (15 psi) or sham injury, and [18F]FDG uptake was measured before injury and again at 1-3 h and 7 days post-injury, using both volume-of-interest (VOI) and voxel-based analysis. VOI analysis revealed significantly increased [18F]FDG uptake in corpus callosum and amygdala at both 1-3 h and 7 days following blast, while a transient decrease in uptake was observed in the midbrain at 1-3 h only. Voxel-based analysis revealed similar significant differences in uptake between sham and blast-injured rats at both time points. At 1-3 h post-injury, clusters of increased uptake were found in the amygdala, somatosensory cortex, and corpus callosum, while regions of decreased uptake were observed in midbrain structures (inferior colliculus, ventrolateral tegmental area) and dorsal auditory cortex. At day 7, a region of increased uptake in blast-injured rats was found in a cluster centered on the cortex-amygdala transition zone, while no regions of decreased uptake were observed. These results suggest that a relatively mild primary blast injury results in altered brain metabolism in multiple brain regions and that post-injury time of assessment is an important factor in observing regional changes in [18F]FDG uptake.

3-D Measurements of Acceleration-Induced Brain Deformation via Harmonic Phase Analysis and Finite-Element Models.

OBJECTIVE: To obtain dense spatiotemporal measurements of brain deformation from two distinct but complementary head motion experiments: linear and rotational accelerations. METHODS: This study introduces a strategy for integrating harmonic phase analysis of tagged magnetic resonance imaging (MRI) and finite-element models to extract mechanically representative deformation measurements. The method was calibrated using simulated as well as experimental data, demonstrated in a phantom including data with image artifacts, and used to measure brain deformation in human volunteers undergoing rotational and linear acceleration. RESULTS: Evaluation methods yielded a displacement error of 1.1 mm compared to human observers and strain errors between [Formula: see text] for linear acceleration and [Formula: see text] for rotational acceleration. This study also demonstrates an approach that can reduce error by 86% in the presence of corrupted data. Analysis of results shows consistency with 2-D motion estimation, agreement with external sensors, and the expected physical behavior of the brain. CONCLUSION: Mechanical regularization is useful for obtaining dense spatiotemporal measurements of in vivo brain deformation under different loading regimes. SIGNIFICANCE: The measurements suggest that the brain's 3-D response to mild accelerations includes distinct patterns observable using practical MRI resolutions. This type of measurement can provide validation data for computer models for the study of traumatic brain injury.

Statistical Characterization of Human Brain Deformation During Mild Angular Acceleration Measured In Vivo by Tagged Magnetic Resonance Imaging.

Understanding of in vivo brain biomechanical behavior is critical in the study of traumatic brain injury (TBI) mechanisms and prevention. Using tagged magnetic resonance imaging, we measured spatiotemporal brain deformations in 34 healthy human volunteers under mild angular accelerations of the head. Two-dimensional (2D) Lagrangian strains were examined throughout the brain in each subject. Strain metrics peaked shortly after contact with a padded stop, corresponding to the inertial response of the brain after head deceleration. Maximum shear strain of at least 3% was experienced at peak deformation by an area fraction (median±standard error) of 23.5±1.8% of cortical gray matter, 15.9±1.4% of white matter, and 4.0±1.5% of deep gray matter. Cortical gray matter strains were greater in the temporal cortex on the side of the initial contact with the padded stop and also in the contralateral temporal, frontal, and parietal cortex. These tissue-level deformations from a population of healthy volunteers provide the first in vivo measurements of full-volume brain deformation in response to known kinematics. Although strains differed in different tissue type and cortical lobes, no significant differences between male and female head accelerations or strain metrics were found. These cumulative results highlight important kinematic features of the brain's mechanical response and can be used to facilitate the evaluation of computational simulations of TBI.

A Three-Dimensional Computational Human Head Model That Captures Live Human Brain Dynamics.

Diffuse axonal injury (DAI) is a debilitating consequence of traumatic brain injury (TBI) attributed to abnormal stretching of axons caused by blunt head trauma or acceleration of the head. We developed an anatomically accurate, subject-specific, three-dimensional (3D) computational model of the human brain, and used it to study the dynamic deformations in the substructures of the brain when the head is subjected to rotational accelerations. The computational head models use anatomy and morphology of the white matter fibers obtained using MRI. Subject-specific full-field shearing motions in live human brains obtained through a recently developed tagged MRI imaging technique are then used to validate the models by comparing the measured and predicted heterogeneous dynamic mechanical response of the brain. These results are used to elucidate the dynamics of local shearing deformations in the brain substructures caused by rotational acceleration of the head. Our work demonstrates that the rotational dynamics of the brain has a timescale of ∼100 ms as determined by the shearing wave speeds, and thus the injuries associated with rotational accelerations likely occur over these time scales. After subject-specific validation using the live human subject data, a representative subject-specific head model is used to simulate a real life scenario that resulted in a concussive injury. Results suggest that regions of the brain, in the form of a toroid, encompassing the white matter, the cortical gray matter, and outer parts of the limbic system have a higher susceptibility to injury under axial rotations of the head.

Three-dimensional regional strain computation method with displacement encoding with stimulated echoes (DENSE) in non-ischemic, non-valvular dilated cardiomyopathy patients and healthy subjects validated by tagged MRI.

PURPOSE: Fast cine displacement encoding with stimulated echoes (DENSE) MR has higher spatial resolution and enables rapid postprocessing. Thus we compared the accuracy of regional strains computation by DENSE with tagged MR in healthy and non-ischemic, non-valvular dilated cardiomyopathy (DCM) subjects. MATERIALS AND METHODS: Validation of three-dimensional regional strains computed with DENSE was conducted in reference to standard tagged MRI (TMRI) in healthy subjects and patients with DCM. Additional repeatability studies in healthy subjects were conducted to increase confidence in DENSE. A meshfree multiquadrics radial point interpolation method (RPIM) was used for computing Lagrange strains in sixteen left ventricular segments. Bland-Altman analysis and Student's t-tests were conducted to observe similarities in regional strains between sequences and in DENSE repeatability studies. RESULTS: Regional circumferential strains ranged from -0.21 ± 0.07 (Lateral-Apex) to -0.11 ± 0.05 (Posterorseptal-Base) in healthy subjects and -0.15 ± 0.04 (Anterior-Apex) to -0.02 ± 0.08 (Posterorseptal-Base) in DCM patients. Computed mean differences in regional circumferential strain from the DENSE-TMRI comparison study was 0.01 ± 0.03 (95% limits of agreement) in normal subjects, -0.01 ± 0.06 in DCM patients and 0.0 ± 0.02 in repeatability studies, with similar agreements in longitudinal and radial strains. CONCLUSION: We found agreement between DENSE and tagged MR in patients and volunteers in terms of evaluation of regional strains.

Improved measurement of brain deformation during mild head acceleration using a novel tagged MRI sequence.

In vivo measurements of human brain deformation during mild acceleration are needed to help validate computational models of traumatic brain injury and to understand the factors that govern the mechanical response of the brain. Tagged magnetic resonance imaging is a powerful, noninvasive technique to track tissue motion in vivo which has been used to quantify brain deformation in live human subjects. However, these prior studies required from 72 to 144 head rotations to generate deformation data for a single image slice, precluding its use to investigate the entire brain in a single subject. Here, a novel method is introduced that significantly reduces temporal variability in the acquisition and improves the accuracy of displacement estimates. Optimization of the acquisition parameters in a gelatin phantom and three human subjects leads to a reduction in the number of rotations from 72 to 144 to as few as 8 for a single image slice. The ability to estimate accurate, well-resolved, fields of displacement and strain in far fewer repetitions will enable comprehensive studies of acceleration-induced deformation throughout the human brain in vivo.