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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, [Formula: see text] , shear anisotropy, [Formula: see text] , and tensile anisotropy, [Formula: see text]. We calculate these anisotropic parameters in the corpus callosum body and find the mean values as [Formula: see text] = 3.78 kPa, [Formula: see text] = 0.151, and [Formula: see text] = 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.

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.

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.

The utility of harmonic phase (HARP) analysis has recently been demonstrated in humans and large animals as a technique for rapid and automatic analysis of tagged MR images. In the current study, the applicability and accuracy of HARP analysis for automatic strain quantification in small animals were investigated. A validation study was performed on seven post-infarct rats and seven age-matched controls. A method for direct computation of 2D Lagrangian strain fields from spatial derivatives of HARP images was also developed in this paper. The results of HARP analysis were evaluated by comparison with those of homogeneous strain analysis employing finite element method and manual tag tracking. Both methods were validated with simulated digital images. Compared to conventional homogeneous strain analysis, HARP analysis yielded similar results in the assessment of regional strain patterns in both control and infarct rats. Both methods detected a reduction in maximal stretch and shortening in infarct rats. Our results suggest that HARP analysis can also be applied to quantify alterations in regional myocardial wall motion in small animals.

Magnetic resonance elastography (MRE) is an imaging modality with which mechanical properties can be noninvasively measured in living tissue. Magnetic resonance elastography relies on the fact that the elastic shear modulus determines the phase velocity and, hence the wavelength, of shear waves which are visualized by motion-sensitive MR imaging. Local frequency estimation (LFE) has been used to extract the local wavenumber from displacement wave fields recorded by MRE. LFE -based inversion is attractive because it allows material parameters to be estimated without explicitly invoking the equations governing wave propagation, thus obviating the need to numerically compute the Laplacian. Nevertheless, studies using LFE have not explicitly addressed three important issues: (1) tissue viscoelasticity; (2) the effects of longitudinal waves and rigid body motion on estimates of shear modulus; and (3) mechanical anisotropy. In the current study we extend the LFE technique to (1) estimate the (complex) viscoelastic shear modulus in lossy media; (2) eliminate the effects of longitudinal waves and rigid body motion; and (3) determine two distinct shear moduli in anisotropic media. The extended LFE approach is demonstrated by analyzing experimental data from a previously-characterized, isotropic, viscoelastic, gelatin phantom and simulated data from a computer model of anisotropic (transversely isotropic) soft material.

Folding of the cerebral cortex is a critical phase of brain development in higher mammals but the biomechanics of folding remain incompletely understood. During folding, the growth of the cortical surface is heterogeneous and anisotropic. We developed and applied a new technique to measure spatial and directional variations in surface growth from longitudinal magnetic resonance imaging (MRI) studies of a single animal or human subject. MRI provides high resolution 3D image volumes of the brain at different stages of development. Surface representations of the cerebral cortex are obtained by segmentation of these volumes. Estimation of local surface growth between two times requires establishment of a point-to-point correspondence (“registration”) between surfaces measured at those times. Here we present a novel approach for the registration of two surfaces in which an energy function is minimized by solving a partial differential equation on a spherical surface. The energy function includes a strain-energy term due to distortion and an “error energy” term due to mismatch between surface features. This algorithm, implemented with the finite element method, brings surface features into approximate alignment while minimizing deformation in regions without explicit matching criteria. The method was validated by application to three simulated test cases and applied to characterize growth of the ferret cortex during folding. Cortical surfaces were created from MRI data acquired in vivo at 14 days, 21 days, and 28 days of life. Deformation gradient and Lagrangian strain tensors describe the kinematics of growth over this interval. These quantitative results illuminate the spatial, temporal, and directional patterns of growth during cortical folding.

Mechanical forces play an important role during brain development. In the early embryo, the anterior end of the neural tube enlarges and differentiates into the major brain subdivisions, including three expanding vesicles (forebrain, midbrain, and hindbrain) separated by two constrictions. Once the anterior neuropore and the spinal neurocoel occlude, the brain tube undergoes further regional growth and expansion in response to increasing cerebrospinal fluid pressure. Although this is known to be a response to mechanical loads, the mechanical properties of the developing brain remain largely unknown. In this work, we measured regional opening angles (due to residual stress) and stiffness of the embryonic chick brain during Hamburger–Hamilton stages 11–13 (approximately 42–51 h incubation). Opening angles resulting from a radial cut on transverse brain slices were about 40–110 deg (depending on region and stage) and served as an indicator of circumferential residual stress. In addition, using a custom-made microindentation device and finite-element models, we determined regional indentation stiffness and material properties. The results indicate that the modulus is relatively independent of position and stage of development with the average shear modulus being about 220 Pa for stages 11–13 chick brains. Information on the regional material properties of the early embryonic brain will help illuminate the process of early brain morphogenesis.

During morphogenesis, epithelia (cell sheets) undergo complex deformations as they stretch, bend, and twist to form the embryo. Often these changes in shape create multivalued surfaces that can be problematic for strain measurements. This paper presents a method for quantifying deformation of such surfaces. The method requires four-dimensional spatiotemporal coordinates of a finite number of surface markers, acquired using standard imaging techniques. From the coordinates of the markers, various deformation measures are computed as functions of time and space using straightforward matrix algebra. This method accommodates sparse randomly scattered marker arrays, with reasonable errors in marker locations. The accuracy of the method is examined for some sample problems with exact solutions. Then, the utility of the method is illustrated by using it to measure surface stretch ratios and shear in the looping heart and developing brain of the early chick embryo. In these examples, microspheres are tracked using optical coherence tomography. This technique provides a new tool that can be used in studies of the mechanics of morphogenesis.

Vibrational loading can stimulate the formation of new trabecular bone or maintain bone mass. Studies investigating vibrational loading have often used whole-body vibration (WBV) as their loading method. However, WBV has limitations in small animal studies because transmissibility of vibration is dependent on posture. In this study, we propose constrained tibial vibration (CTV) as an experimental method for vibrational loading of mice under controlled conditions. In CTV, the lower leg of an anesthetized mouse is subjected to vertical vibrational loading while supporting a mass. The setup approximates a one degree-of-freedom vibrational system. Accelerometers were used to measure transmissibility of vibration through the lower leg in CTV at frequencies from 20 Hz to 150 Hz. First, the frequency response of transmissibility was quantified in vivo, and dissections were performed to remove one component of the mouse leg (the knee joint, foot, or soft tissue) to investigate the contribution of each component to the frequency response of the intact leg. Next, a finite element (FE) model of a mouse tibia-fibula was used to estimate the deformation of the bone during CTV. Finally, strain gages were used to determine the dependence of bone strain on loading frequency. The in vivo mouse leg in the CTV system had a resonant frequency of 60 Hz for +/-0.5 G vibration (1.0 G peak to peak). Removing the foot caused the natural frequency of the system to shift from 60 Hz to 70 Hz, removing the soft tissue caused no change in natural frequency, and removing the knee changed the natural frequency from 60 Hz to 90 Hz. By using the FE model, maximum tensile and compressive strains during CTV were estimated to be on the cranial-medial and caudolateral surfaces of the tibia, respectively, and the peak transmissibility and peak cortical strain occurred at the same frequency. Strain gage data confirmed the relationship between peak transmissibility and peak bone strain indicated by the FE model, and showed that the maximum cyclic tibial strain during CTV of the intact leg was 330+/-82microepsilon and occurred at 60-70 Hz. This study presents a comprehensive mechanical analysis of CTV, a loading method for studying vibrational loading under controlled conditions. This model will be used in future in vivo studies and will potentially become an important tool for understanding the response of bone to vibrational loading.

Understanding the brain’s response to multiple loadings requires knowledge of how straining changes the mechanical response of brain tissue. We studied the inelastic behavior of bovine white matter and found that when this tissue is stretched beyond a critical strain threshold, its reloading stiffness drops. An upper bound for this strain threshold was characterized, and was found to be strain rate dependent at low strain rates and strain rate independent at higher strain rates. Results suggest that permanent changes to tissue mechanics can occur at strains below those believed to cause physiological disruption or rupture of axons. Such behavior is characteristic of disentanglement in fibrous-networked solids, in which strain-induced mechanical changes may result from fiber realignment rather than fiber breakage.

In this study, the magnetic resonance (MR) elastography technique was used to estimate the dynamic shear modulus of mouse brain tissue in vivo. The technique allows visualization and measurement of mechanical shear waves excited by lateral vibration of the skull. Quantitative measurements of displacement in three dimensions during vibration at 1200Hz were obtained by applying oscillatory magnetic field gradients at the same frequency during a MR imaging sequence. Contrast in the resulting phase images of the mouse brain is proportional to displacement. To obtain estimates of shear modulus, measured displacement fields were fitted to the shear wave equation. Validation of the procedure was performed on gel characterized by independent rheometry tests and on data from finite element simulations. Brain tissue is, in reality, viscoelastic and nonlinear. The current estimates of dynamic shear modulus are strictly relevant only to small oscillations at a specific frequency, but these estimates may be obtained at high frequencies (and thus high deformation rates), noninvasively throughout the brain. These data complement measurements of nonlinear viscoelastic properties obtained by others at slower rates, either ex vivo or invasively.