Post-mortem changes of anisotropic mechanical properties in the porcine brain assessed by MR elastography.

Knowledge of the mechanical properties of brain tissue in vivo is essential to understanding the mechanisms underlying traumatic brain injury (TBI) and to creating accurate computational models of TBI and neurosurgical simulation. Brain white matter, which is composed of aligned, myelinated, axonal fibers, is structurally anisotropic. White matter in vivo also exhibits mechanical anisotropy, as measured by magnetic resonance elastography (MRE), but measurements of anisotropy obtained by mechanical testing of white matter ex vivo have been inconsistent. The minipig has a gyrencephalic brain with similar white matter and gray matter proportions to humans and therefore provides a relevant model for human brain mechanics. In this study, we compare estimates of anisotropic mechanical properties of the minipig brain obtained by identical, non-invasive methods in the live (in vivo) and dead animals (in situ). To do so, we combine wave displacement fields from MRE and fiber directions derived from diffusion tensor imaging (DTI) with a finite element-based, transversely-isotropic nonlinear inversion (TI-NLI) algorithm. Maps of anisotropic mechanical properties in the minipig brain were generated for each animal alive and at specific times post-mortem. These maps show that white matter is stiffer, more dissipative, and more anisotropic than gray matter when the minipig is alive, but that these differences largely disappear post-mortem, with the exception of tensile anisotropy. Overall, brain tissue becomes stiffer, less dissipative, and less mechanically anisotropic post-mortem. These findings emphasize the importance of testing brain tissue properties in vivo. Statement of Significance: In this study, MRE and DTI in the minipig were combined to estimate, for the first time, anisotropic mechanical properties in the living brain and in the same brain after death. Significant differences were observed in the anisotropic behavior of brain tissue post-mortem. These results demonstrate the importance of measuring brain tissue properties in vivo as well as ex vivo, and provide new quantitative data for the development of computational models of brain biomechanics.

Shear wave speeds in a nearly incompressible fibrous material with two unequal fiber families.

The mechanical properties of soft biological tissues can be characterized non-invasively by magnetic resonance elastography (MRE). In MRE, shear wave fields are induced by vibration, imaged by magnetic resonance imaging, and inverted to estimate tissue properties in terms of the parameters of an underlying material model. Most MRE studies assume an isotropic material model; however, biological tissue is often anisotropic with a fibrous structure, and some tissues contain two or more families of fibers-each with different orientations and properties. Motivated by the prospect of using MRE to characterize such tissues, this paper describes the propagation of shear waves in soft fibrous material with two unequal fiber families. Shear wave speeds are expressed in terms of material parameters, and the effect of each parameter on the shear wave speeds is investigated. Analytical expressions of wave speeds are confirmed by finite element simulations of shear wave transmission with various polarization directions. This study supports the feasibility of estimating parameters of soft fibrous tissues with two unequal fiber families in vivo from local shear wave speeds and advances the prospects for the mechanical characterization of such biological tissues by MRE.

Effect of Direction and Frequency of Skull Motion on Mechanical Vulnerability of the Human Brain.

Strain energy and kinetic energy in the human brain were estimated by magnetic resonance elastography (MRE) during harmonic excitation of the head, and compared to characterize the effect of loading direction and frequency on brain deformation. In brain MRE, shear waves are induced by external vibration of the skull and imaged by a modified MR imaging sequence; the resulting harmonic displacement fields are typically "inverted" to estimate mechanical properties, like stiffness or damping. However, measurements of tissue motion from MRE also illuminate key features of the response of the brain to skull loading. In this study, harmonic excitation was applied in two different directions and at five different frequencies from 20 to 90 Hz. Lateral loading induced primarily left-right head motion and rotation in the axial plane; occipital loading induced anterior-posterior head motion and rotation in the sagittal plane. The ratio of strain energy to kinetic energy (SE/KE) depended strongly on both direction and frequency. The ratio of SE/KE was approximately four times larger for lateral excitation than for occipital excitation and was largest at the lowest excitation frequencies studied. These results are consistent with clinical observations that suggest lateral impacts are more likely to cause injury than occipital or frontal impacts, and also with observations that the brain has low-frequency (∼10 Hz) natural modes of oscillation. The SE/KE ratio from brain MRE is potentially a simple and powerful dimensionless metric of brain vulnerability to deformation and injury.

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.

Measurement of relative motion of the brain and skull in the mini-pig in-vivo.

The mechanical role of the skull-brain interface is critical to the pathology of concussion and traumatic brain injury (TBI) and may evolve with age. Here we characterize the skull-brain interface in juvenile, female Yucatan mini-pigs from 3 to 6 months old using techniques from magnetic resonance elastography (MRE). The displacements of the skull and brain were measured by a motion-sensitive MR imaging sequence during low-amplitude harmonic motion of the head. Each animal was scanned four times at 1-month intervals. Harmonic motion at 100 Hz was excited by three different configurations of a jaw actuator in order to vary the direction of loading. Rigid-body linear motions of the brain and skull were similar, although brain rotations were consistently smaller than corresponding skull rotations. Relative displacements between the brain and skull were estimated for voxels on the surface of the brain. Amplitudes of relative displacements between skull and brain were 1-3 µm, approximately 25-50% of corresponding skull displacements. Maps of relative displacement showed variations by anatomical region, and the normal component of relative displacement was consistently 25-50% of the tangential component. These results illuminate the mechanics of the skull-brain interface in a gyrencephalic animal model relevant to human brain injury and development.

Mechanical stiffness and anisotropy measured by MRE during brain development in the minipig.

The relationship between brain development and mechanical properties of brain tissue is important, but remains incompletely understood, in part due to the challenges in measuring these properties longitudinally over time. In addition, white matter, which is composed of aligned, myelinated, axonal fibers, may be mechanically anisotropic. Here we use data from magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) to estimate anisotropic mechanical properties in six female Yucatan minipigs at ages from 3 to 6 months. Fiber direction was estimated from the principal axis of the diffusion tensor in each voxel. Harmonic shear waves in the brain were excited by three different configurations of a jaw actuator and measured using a motion-sensitive MR imaging sequence. Anisotropic mechanical properties are estimated from displacement field and fiber direction data with a finite element- based, transversely-isotropic nonlinear inversion (TI-NLI) algorithm. TI-NLI finds spatially resolved TI material properties that minimize the error between measured and simulated displacement fields. Maps of anisotropic mechanical properties in the minipig brain were generated for each animal at all four ages. These maps show that white matter is more dissipative and anisotropic than gray matter, and reveal significant effects of brain development on brain stiffness and structural anisotropy. Changes in brain mechanical properties may be a fundamental biophysical signature of brain development.

Design and characterization of 3-D printed hydrogel lattices with anisotropic mechanical properties.

The goal of this study was to design, fabricate, and characterize hydrogel lattice structures with consistent, controllable, anisotropic mechanical properties. Lattices, based on three unit-cell types (cubic, diamond, and vintile), were printed using stereolithography (SLA) of polyethylene glycol diacrylate (PEGDA). To create structural anisotropy in the lattices, unit cell design files were scaled by a factor of two in one direction in each layer and then printed. The mechanical properties of the scaled lattices were measured in shear and compression and compared to those of the unscaled lattices. Two apparent shear moduli of each lattice were measured by dynamic shear tests in two planes: (1) parallel and (2) perpendicular to the scaling direction, or cell symmetry axis. Three apparent Young's moduli of each lattice were measured by compression in three different directions: (1) the "build" direction or direction of added layers, (2) the scaling direction, and (3) the unscaled direction perpendicular to both scaling and build directions. For shear deformation in unscaled lattices, the apparent shear moduli were similar in the two perpendicular directions. In contrast, scaled lattices exhibit clear differences in apparent shear moduli. In compression of unscaled lattices, apparent Young's moduli were independent of direction in cubic and vintile lattices; in diamond lattices Young's moduli differed in the build direction, but were similar in the other two directions. Scaled lattices in compression exhibited additional differences in apparent Young's moduli in the scaled and unscaled directions. Notably, the effects of scaling on apparent modulus differed between each lattice type (cubic, diamond, or vintile) and deformation mode (shear or compression). Scaling of 3D-printed, hydrogel lattices may be harnessed to create tunable, structures of desired shape, stiffness, and mechanical anisotropy, in both shear and compression.

Anisotropic mechanical properties in the healthy human brain estimated with multi-excitation transversely isotropic MR elastography.

Magnetic resonance elastography (MRE) is an MRI technique for imaging the mechanical properties of brain in vivo, and has shown differences in properties between neuroanatomical regions and sensitivity to aging, neurological disorders, and normal brain function. Past MRE studies investigating these properties have typically assumed the brain is mechanically isotropic, though the aligned fibers of white matter suggest an anisotropic material model should be considered for more accurate parameter estimation. Here we used a transversely isotropic, nonlinear inversion algorithm (TI-NLI) and multiexcitation MRE to estimate the anisotropic material parameters of individual white matter tracts in healthy young adults. We found significant differences between individual tracts for three recovered anisotropic parameters: substrate shear stiffness, µ (range: 2.57 - 3.02 kPa), shear anisotropy, ϕ (range: -0.026 - 0.164), and tensile anisotropy, ζ (range: 0.559 - 1.049). Additionally, we demonstrated the repeatability of these parameter estimates in terms of lower variability of repeated measures in a single subject relative to variability in our sample population. Further, we observed significant differences in anisotropic mechanical properties between segments of the corpus callosum (genu, body, and splenium), which is expected based on differences in axonal microstructure. This study shows the ability of MRE with TI-NLI to estimate anisotropic mechanical properties of white matter and presents reference properties for tracts throughout the healthy brain.

Estimation of the mechanical properties of a transversely isotropic material from shear wave fields via artificial neural networks.

Artificial neural networks (ANN), established tools in machine learning, are applied to the problem of estimating parameters of a transversely isotropic (TI) material model using data from magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI). We use neural networks to estimate parameters from experimental measurements of ultrasound-induced shear waves after training on analogous data from simulations of a computer model with similar loading, geometry, and boundary conditions. Strain ratios and shear-wave speeds (from MRE) and fiber direction (the direction of maximum diffusivity from diffusion tensor imaging (DTI)) are used as inputs to neural networks trained to estimate the parameters of a TI material (baseline shear modulus µ, shear anisotropy φ, and tensile anisotropy ζ). Ensembles of neural networks are applied to obtain distributions of parameter estimates. The robustness of this approach is assessed by quantifying the sensitivity of property estimates to assumptions in modeling (such as assumed loss factor) and choices in fitting (such as the size of the neural network). This study demonstrates the successful application of simulation-trained neural networks to estimate anisotropic material parameters from complementary MRE and DTI imaging data.

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.

Simulation of harmonic shear waves in the human brain and comparison with measurements from magnetic resonance elastography.

Magnetic Resonance Elastography (MRE) provides a non-invasive method to characterize the mechanical response of the living brain subjected to harmonic loading conditions. The peak magnitude of the harmonic strain is small and the excitation results in harmless deformation waves propagating through the brain. In this paper, we describe a three-dimensional computational model of the brain for comparison of simulated harmonic deformations of the brain with MRE measurements. Relevant substructures of the head were constructed from MRI scans. Harmonic wave motions in a live human brain obtained in an MRE experiment were used to calibrate the viscoelastic properties at 50 Hz and assess accuracy of the computational model by comparing the measured and the simulated harmonic response of the brain. Quantitative comparison of strain field from simulations with measured data from MRE shows that the harmonic deformation of the brain tissue is responsive to changes in the viscoelastic properties, loss and storage moduli, of the brain. The simulation results demonstrate, in agreement with MRE measurements, that the presence of the falx and tentorium membranes alter the spatial distribution of harmonic deformation field and peak strain amplitudes in the computational model of the brain.

Shear wave speeds in nearly-incompressible fibrous materials with two fiber families.

An analytical and numerical investigation of shear wave behavior in nearly-incompressible soft materials with two fiber families was performed, focusing on the effects of material parameters and imposed pre-deformations on wave speed. This theoretical study is motivated by the emerging ability to image shear waves in soft biological tissues by magnetic resonance elastography (MRE). In MRE, the relationships between wave behavior and mechanical properties can be used to characterize tissue properties non-invasively. We demonstrate these principles in two material models, each with two fiber families. One model is a nearly-incompressible linear elastic model that exhibits both shear and tensile anisotropy; the other is a two-fiber-family version of the widely-used Holzapfel-Gasser-Ogden (HGO) model, which is nonlinear. Shear waves can be used to probe nonlinear material behavior using infinitesimal dynamic deformations superimposed on larger, quasi-static "pre-deformations." In this study, closed-form expressions for shear wave speeds in the HGO model are obtained in terms of the model parameters and imposed pre-deformations. Analytical expressions for wave speeds are confirmed by finite element simulations of shear waves with various polarizations and propagation directions. These studies support the feasibility of estimating the parameters of an HGO material model noninvasively from measured shear wave speeds.

A heterogenous, time harmonic, nearly incompressible transverse isotropic finite element brain simulation platform for MR elastography.

In this study, we describe numerical implementation of a heterogenous, nearly incompressible, transverse isotropic (NITI) finite element (FE) model with key advantages for use in MR elastography of fibrous soft tissue. MR elastography (MRE) estimates heterogenous property distributions from MR-measured harmonic motion fields based on assumed mechanical models of tissue response. Current MRE property estimation methods usually assume isotropic properties, which cause inconsistencies arising from model-data mismatch when anisotropy is present. In this study, we use a NITI model parameterized by a base shear modulus, shear anisotropy, tensile anisotropy, and an isotropic bulk modulus, which describes the mechanical behavior of tissues with aligned fiber structures well. Property and fiber direction heterogeneity are implemented at the level of FE Gauss points, which allows high-resolution diffusion tensor imaging (DTI) data to be incorporated easily into the model. The resulting code was validated against analytical solutions and a commercial FEM package, and is suitable for incorporation into nonlinear inversion MRE algorithms. Simulations of MRE in brain tissue with heterogeneous properties and anisotropic fiber tracts, which produced wavefields similar to experimental MRE, were generated from anatomical, DTI and MRE image data, allowing investigation of MRE inversion performance in a realistic setting where the ground truth and underlying mechanical behavior are known. Two established isotropic inversion algorithms-nonlinear inversion (NLI) and local direct inversion (LDI)-were applied to simulated MRE data. Both algorithms performed well in simple isotropic homogenous cases; however, heterogeneity cased substantial artifacts in LDI arising from violation of local homogeneity assumptions. NLI was able to recover accurate heterogenous displacement fields in the presence of measurement noise. Isotropic NLI inversion of simulated anisotropic data (generated using the NITI model) produced maps of isotropic mechanical properties with undesirable dependence on the wavefield. Local anisotropy also caused wavefield-dependent errors of 7% in nearby isotropic structures, compared to 10% in the anisotropic structures.

Multi-Excitation Magnetic Resonance Elastography of the Brain: Wave Propagation in Anisotropic White Matter.

Magnetic resonance elastography (MRE) has emerged as a sensitive imaging technique capable of providing a quantitative understanding of neural microstructural integrity. However, a reliable method for the quantification of the anisotropic mechanical properties of human white matter is currently lacking, despite the potential to illuminate the pathophysiology behind neurological disorders and traumatic brain injury. In this study, we examine the use of multiple excitations in MRE to generate wave displacement data sufficient for anisotropic inversion in white matter. We show the presence of multiple unique waves from each excitation which we combine to solve for parameters of an incompressible, transversely isotropic (ITI) material: shear modulus, µ, shear anisotropy, ϕ, and tensile anisotropy, ζ. We calculate these anisotropic parameters in the corpus callosum body and find the mean values as µ = 3.78 kPa, ϕ = 0.151, and ζ = 0.099 (at 50 Hz vibration frequency). This study demonstrates that multi-excitation MRE provides displacement data sufficient for the evaluation of the anisotropic properties of white matter.

Estimation of Anisotropic Material Properties of Soft Tissue by MRI of Ultrasound-Induced Shear Waves.

This paper describes a new method for estimating anisotropic mechanical properties of fibrous soft tissue by imaging shear waves induced by focused ultrasound (FUS) and analyzing their direction-dependent speeds. Fibrous materials with a single, dominant fiber direction may exhibit anisotropy in both shear and tensile moduli, reflecting differences in the response of the material when loads are applied in different directions. The speeds of shear waves in such materials depend on the propagation and polarization directions of the waves relative to the dominant fiber direction. In this study, shear waves were induced in muscle tissue (chicken breast) ex vivo by harmonically oscillating the amplitude of an ultrasound beam focused in a cylindrical tissue sample. The orientation of the fiber direction relative to the excitation direction was varied by rotating the sample. Magnetic resonance elastography (MRE) was used to visualize and measure the full 3D displacement field due to the ultrasound-induced shear waves. The phase gradient (PG) of radially propagating "slow" and "fast" shear waves provided local estimates of their respective wave speeds and directions. The equations for the speeds of these waves in an incompressible, transversely isotropic (TI), linear elastic material were fitted to measurements to estimate the shear and tensile moduli of the material. The combination of focused ultrasound and MR imaging allows noninvasive, but comprehensive, characterization of anisotropic soft tissue.

Shear Wave Propagation and Estimation of Material Parameters in a Nonlinear, Fibrous Material.

This paper describes the propagation of shear waves in a Holzapfel-Gasser-Ogden (HGO) material and investigates the potential of magnetic resonance elastography (MRE) for estimating parameters of the HGO material model from experimental data. In most MRE studies the behavior of the material is assumed to be governed by linear, isotropic elasticity or viscoelasticity. In contrast, biological tissue is often nonlinear and anisotropic with a fibrous structure. In such materials, application of a quasi-static deformation (predeformation) plays an important role in shear wave propagation. Closed form expressions for shear wave speeds in an HGO material with a single family of fibers were found in a reference (undeformed) configuration and after imposed predeformations. These analytical expressions show that shear wave speeds are affected by the parameters (µ0, k1, k2, κ) of the HGO model and by the direction and amplitude of the predeformations. Simulations of corresponding finite element (FE) models confirm the predicted influence of HGO model parameters on speeds of shear waves with specific polarization and propagation directions. Importantly, the dependence of wave speeds on the parameters of the HGO model and imposed deformations could ultimately allow the noninvasive estimation of material parameters in vivo from experimental shear wave image data.

Insights Into Traumatic Brain Injury From MRI of Harmonic Brain Motion.

Measurements of dynamic deformation of the human brain, induced by external harmonic vibration of the skull, were analyzed to illuminate the mechanics of mild traumatic brain injury (TBI). Shear wave propagation velocity vector fields were obtained to illustrate the role of the skull and stiff internal membranes in transmitting motion to the brain. Relative motion between the cerebrum and cerebellum was quantified to assess the vulnerability of connecting structures. Mechanical deformation was quantified throughout the brain to investigate spatial patterns of strain and axonal stretch. Strain magnitude was generally attenuated as shear waves propagated into interior structures of the brain; this attenuation was greater at higher frequencies. Analysis of shear wave propagation direction indicates that the stiff membranes (falx and tentorium) greatly affect brain deformation during imposed skull motion as they serve as sites for both initiation and reflection of shear waves. Relative motion between the cerebellum and cerebrum was small in comparison with the overall motion of both structures, which suggests that such relative motion might play only a minor role in TBI mechanics. Strain magnitudes and the amount of axonal stretch near the bases of sulci were similar to those in other areas of the cortex, and local strain concentrations at the gray-white matter boundary were not observed. We tentatively conclude that observed differences in neuropathological response in these areas might be due to heterogeneity in the response to mechanical deformation rather than heterogeneity of the deformation itself.

Relationships between scalp, brain, and skull motion estimated using magnetic resonance elastography.

The objective of this study was to characterize the relationships between motion in the scalp, skull, and brain. In vivo estimates of motion transmission from the skull to the brain may illuminate the mechanics of traumatic brain injury. Because of challenges in directly sensing skull motion, it is useful to know how well motion of soft tissue of the head, i.e., the scalp, can approximate skull motion or predict brain tissue deformation. In this study, motion of the scalp and brain were measured using magnetic resonance elastography (MRE) and separated into components due to rigid-body displacement and dynamic deformation. Displacement estimates in the scalp were calculated using low motion-encoding gradient strength in order to reduce "phase wrapping" (an ambiguity in displacement estimates caused by the 2 π-periodicity of MRE phase contrast). MRE estimates of scalp and brain motion were compared to skull motion estimated from three tri-axial accelerometers. Comparison of the relative amplitudes and phases of harmonic motion in the scalp, skull, and brain of six human subjects indicate that data from scalp-based sensors should be used with caution to estimate skull kinematics, but that fairly consistent relationships exist between scalp, skull, and brain motion. In addition, the measured amplitude and phase relationships of scalp, skull, and brain can be used to evaluate and improve mathematical models of head biomechanics.

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies.

The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies.

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull-brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin "phantom," displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull-brain interface will be valuable in the parameterization and validation of computer models of TBI.