Mechanical Properties of White Matter Tracts in Aging Assessed via Anisotropic MR Elastography.

Magnetic resonance elastography (MRE) is a promising neuroimaging technique to probe tissue microstructure, which has revealed widespread softening with loss of structural integrity in the aging brain. Traditional MRE approaches assume mechanical isotropy. However, white matter is known to be anisotropic from aligned, myelinated axonal bundles, which can lead to uncertainty in mechanical property estimates in these areas when using isotropic MRE. Recent advances in anisotropic MRE now allow for estimation of shear and tensile anisotropy, along with substrate shear modulus, in white matter tracts. The objective of this study was to investigate age-related differences in anisotropic mechanical properties in human brain white matter tracts for the first time. Anisotropic mechanical properties in all tracts were found to be significantly lower in older adults compared to young adults, with average property differences ranging between 0.028-0.107 for shear anisotropy and between 0.139-0.347 for tensile anisotropy. Stiffness perpendicular to the axonal fiber direction was also significantly lower in older age, but only in certain tracts. When compared with fractional anisotropy measures from diffusion tensor imaging, we found that anisotropic MRE measures provided additional, complementary information in describing differences between the white matter integrity of young and older populations. Anisotropic MRE provides a new tool for studying white matter structural integrity in aging and neurodegeneration.

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.

Viscoelastic polyacrylamide MR elastography phantoms with tunable damping ratio independent of shear stiffness.

Physiologically modeled test samples with known properties and characteristics, or phantoms, are essential for developing sensitive, repeatable, and accurate quantitative MRI techniques. Magnetic resonance elastography (MRE) is one such technique used to estimate tissue mechanical properties, and it is advantageous to use phantoms with independently tunable mechanical properties to benchmark the accuracy of MRE methods. Phantoms with tunable shear stiffness are commonly used for MRE, but tuning the viscosity or damping ratio has proven to be difficult. A promising candidate for MRE phantoms with tunable damping ratio is polyacrylamide (PAA). While pure PAA has very low attenuation, viscoelastic hydrogels have been made by entrapping linear polyacrylamide strands (LPAA) within the PAA network. In this study, we evaluate the use of LPAA/PAA gels as physiologically accurate phantoms with tunable damping ratio, independent of shear stiffness, via MRE. Phantoms were made with 15.3 wt% PAA while the LPAA concentration ranged from 4.5 wt% to 8.0 wt%. MRE was performed at 9.4 T with 400 Hz vibration on all phantoms revealing a strong, positive correlation between damping ratio and LPAA content (p < 0.001). There was no significant correlation between shear stiffness and LPAA content, confirming a constant PAA concentration yielded constant shear stiffness. Rheometry at 10 Hz was performed to verify the damping ratio of the phantoms. Nearly identical slopes for damping ratio versus LPAA content were found from both MRE and rheometry (0.0073 and 0.0075 respectively). Ultimately, this study validates the adaptation of polyacrylamide gels into physiologically-relevant MRE phantoms to enable testing of MRE estimates of damping ratio.

Magnetic resonance elastography captures a transient benefit of exercise intervention on forebrain stiffness in a rat model of fetal alcohol spectrum disorders.

BACKGROUND: Fetal alcohol spectrum disorders (FASD), a group of prevalent conditions resulting from prenatal alcohol exposure, affect the maturation of cerebral white matter as first identified with neuroimaging. However, traditional methods are unable to track subtle microstructural alterations to white matter. This preliminary study uses a highly sensitive and clinically translatable magnetic resonance elastography (MRE) protocol to assess brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD. METHODS: Female rat pups were either alcohol-exposed (AE) via intragastric intubation of alcohol in milk substitute (5.25 g/kg/day) or sham-intubated (SI) on postnatal days (PD) four through nine to model alcohol exposure during the brain growth spurt. On PD 30, half of AE and SI rats were randomly assigned to either a wheel-running or standard cage for 12 days. Magnetic resonance elastography was used to measure whole brain and callosal mechanical properties at the end of the intervention (around PD 42) and at 1 month post-intervention, and findings were validated with histological quantification of oligoglia. RESULTS: Alcohol exposure reduced forebrain stiffness (p = 0.02) in standard-housed rats. The adolescent exercise intervention mitigated this effect, confirming that increased aerobic activity supports proper neurodevelopmental trajectories. Forebrain damping ratio was lowest in standard-housed AE rats (p < 0.01), but this effect was not mitigated by intervention exposure. At 1 month post-intervention, all rats exhibited comparable forebrain stiffness and damping ratio (p > 0.05). Callosal stiffness and damping ratio increased with age. With cessation of exercise, there was a negative rebound effect on the quantity of callosal oligodendrocytes, irrespective of treatment group, which diverged from our MRE results. CONCLUSIONS: This is the first application of MRE to measure the brain's mechanical properties in a rodent model of FASD. MRE successfully captured alcohol-related changes in forebrain stiffness and damping ratio. Additionally, MRE identified an exercise-related increase to forebrain stiffness in AE rats.

Monitoring lasting changes to brain tissue integrity through mechanical properties following adolescent exercise intervention in a rat model of Fetal Alcohol Spectrum Disorders.

Background: Fetal Alcohol Spectrum Disorders (FASD) encompass a group of highly prevalent conditions resulting from prenatal alcohol exposure. Alcohol exposure during the third trimester of pregnancy overlapping with the brain growth spurt is detrimental to white matter growth and myelination, particularly in the corpus callosum, ultimately affecting tissue integrity in adolescence. Traditional neuroimaging techniques have been essential for assessing neurodevelopment in affected youth; however, these methods are limited in their capacity to track subtle microstructural alterations to white matter, thus restricting their effectiveness in monitoring therapeutic intervention. In this preliminary study we use a highly sensitive and clinically translatable Magnetic Resonance Elastography (MRE) protocol for assessing brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD. Methods: Rat pups were divided into two groups: alcohol-exposed (AE) pups which received alcohol in milk substitute (5.25 g/kg/day) via intragastric intubation on postnatal days (PD) four through nine during the rat brain growth spurt (Dobbing and Sands, 1979), or sham-intubated (SI) controls. In adolescence, on PD 30, half AE and SI rats were randomly assigned to either a modified home cage with free access to a running wheel or to a new home cage for 12 days (Gursky and Klintsova, 2017). Previous studies conducted in the lab have shown that 12 days of voluntary exercise intervention in adolescence immediately ameliorated callosal myelination in AE rats (Milbocker et al., 2022, 2023). MRE was used to measure longitudinal changes to mechanical properties of the whole brain and the corpus callosum at intervention termination and one-month post-intervention. Histological quantification of precursor and myelinating oligoglia in corpus callosum was performed one-month post-intervention. Results: Prior to intervention, AE rats had lower forebrain stiffness in adolescence compared to SI controls ( p = 0.02). Exercise intervention immediately mitigated this effect in AE rats, resulting in higher forebrain stiffness post-intervention in adolescence. Similarly, we discovered that forebrain damping ratio was lowest in AE rats in adolescence ( p < 0.01), irrespective of intervention exposure. One-month post-intervention in adulthood, AE and SI rats exhibited comparable forebrain stiffness and damping ratio (p > 0.05). Taken together, these MRE data suggest that adolescent exercise intervention supports neurodevelopmental "catch-up" in AE rats. Analysis of the stiffness and damping ratio of the body of corpus callosum revealed that these measures increased with age. Finally, histological quantification of myelinating oligodendrocytes one-month post-intervention revealed a negative rebound effect of exercise cessation on the total estimate of these cells in the body of corpus callosum, irrespective of treatment group which was not convergent with noninvasive MRE measures. Conclusions: This is the first application of MRE to measure changes in brain mechanical properties in a rodent model of FASD. MRE successfully captured alcohol-related changes to forebrain stiffness and damping ratio in adolescence. These preliminary findings expand upon results from previous studies which used traditional diffusion neuroimaging to identify structural changes to the adolescent brain in rodent models of FASD (Milbocker et al., 2022; Newville et al., 2017). Additionally, in vivo MRE identified an exercise-related alteration to forebrain stiffness that occurred in adolescence, immediately post-intervention.

Clinical application of magnetic resonance elastography in pediatric neurological disorders.

Magnetic resonance elastography is a relatively new, rapidly evolving quantitative magnetic resonance imaging technique which can be used for mapping the viscoelastic mechanical properties of soft tissues. MR elastography measurements are akin to manual palpation but with the advantages of both being quantitative and being useful for regions which are not available for palpation, such as the human brain. MR elastography is noninvasive, well tolerated, and complements standard radiological and histopathological studies by providing in vivo measurements that reflect tissue microstructural integrity. While brain MR elastography studies in adults are becoming frequent, published studies on the utility of MR elastography in children are sparse. In this review, we have summarized the major scientific principles and recent clinical applications of brain MR elastography in diagnostic neuroscience and discuss avenues for impact in assessing the pediatric brain.

Individual Muscle Force Estimation in the Human Forearm Using Multi-Muscle MR Elastography (MM-MRE).

OBJECTIVE: To establish the sensitivity of magnetic resonance elastography (MRE) to active muscle contraction in multiple muscles of the forearm. METHODS: We combined MRE of forearm muscles with an MRI-compatible device, the MREbot, to simultaneously measure the mechanical properties of tissues in the forearm and the torque applied by the wrist joint during isometric tasks. We measured shear wave speed of thirteen forearm muscles via MRE in a series of contractile states and wrist postures and fit these outputs to a force estimation algorithm based on a musculoskeletal model. RESULTS: Shear wave speed changed significantly upon several factors, including whether the muscle was recruited as an agonist or antagonist (p = 0.0019), torque amplitude (p = <0.0001), and wrist posture (p = 0.0002). Shear wave speed increased significantly during both agonist (p = <0.0001) and antagonist (p = 0.0448) contraction. Additionally, there was a greater increase in shear wave speed at greater levels of loading. The variations due to these factors indicate the sensitivity to functional loading of muscle. Under the assumption of a quadratic relationship between shear wave speed and muscle force, MRE measurements accounted for an average of 70% of the variance in the measured joint torque. CONCLUSION: This study shows the ability of MM-MRE to capture variations in individual muscle shear wave speed due to muscle activation and presents a method to estimate individual muscle force through MM-MRE derived measurements of shear wave speed. SIGNIFICANCE: MM-MRE could be used to establish normal and abnormal muscle co-contraction patterns in muscles of the forearm controlling hand and wrist function.

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.

In vivoestimation of anisotropic mechanical properties of the gastrocnemius during functional loading with MR elastography.

Objective.In vivoimaging assessments of skeletal muscle structure and function allow for longitudinal quantification of tissue health. Magnetic resonance elastography (MRE) non-invasively quantifies tissue mechanical properties, allowing for evaluation of skeletal muscle biomechanics in response to loading, creating a better understanding of muscle functional health.Approach. In this study, we analyze the anisotropic mechanical response of calf muscles using MRE with a transversely isotropic, nonlinear inversion algorithm (TI-NLI) to investigate the role of muscle fiber stiffening under load. We estimate anisotropic material parameters including fiber shear stiffness (µ1), substrate shear stiffness (µ2), shear anisotropy (ϕ), and tensile anisotropy (ζ) of the gastrocnemius muscle in response to both passive and active tension.Main results. In passive tension, we found a significant increase inµ1,ϕ,andζwith increasing muscle length. While in active tension, we observed increasingµ2and decreasingϕandζduring active dorsiflexion and plantarflexion-indicating less anisotropy-with greater effects when the muscles act as agonist.Significance. The study demonstrates the ability of this anisotropic MRE method to capture the multifaceted mechanical response of skeletal muscle to tissue loading from muscle lengthening and contraction.

Hippocampal subfield viscoelasticity in amnestic mild cognitive impairment evaluated with MR elastography.

Hippocampal subfields (HCsf) are brain regions important for memory function that are vulnerable to decline with amnestic mild cognitive impairment (aMCI), which is often a preclinical stage of Alzheimer's disease. Studies in aMCI patients often assess HCsf tissue integrity using measures of volume, which has little specificity to microstructure and pathology. We use magnetic resonance elastography (MRE) to examine the viscoelastic mechanical properties of HCsf tissue, which is related to structural integrity, and sensitively detect differences in older adults with aMCI compared to an age-matched control group. Group comparisons revealed HCsf viscoelasticity is differentially affected in aMCI, with CA1-CA2 and DG-CA3 exhibiting lower stiffness and CA1-CA2 exhibiting higher damping ratio, both indicating poorer tissue integrity in aMCI. Including HCsf stiffness in a logistic regression improves classification of aMCI beyond measures of volume alone. Additionally, lower DG-CA3 stiffness predicted aMCI status regardless of DG-CA3 volume. These findings showcase the benefit of using MRE in detecting subtle pathological tissue changes in individuals with aMCI via the HCsf particularly affected in the disease.

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.

Structure-Function Dissociations of Human Hippocampal Subfield Stiffness and Memory Performance.

Aging and neurodegenerative diseases lead to decline in thinking and memory ability. The subfields of the hippocampus (HCsf) play important roles in memory formation and recall. Imaging techniques sensitive to the underlying HCsf tissue microstructure can reveal unique structure-function associations and their vulnerability in aging and disease. The goal of this study was to use magnetic resonance elastography (MRE), a noninvasive MR imaging-based technique that can quantitatively image the viscoelastic mechanical properties of tissue to determine the associations of HCsf stiffness with different cognitive domains across the lifespan. Eighty-eight adult participants completed the study (age 23-81 years, male/female 36/51), in which we aimed to determine which HCsf regions most strongly correlated with different memory performance outcomes and if viscoelasticity of specific HCsf regions mediated the relationship between age and performance. Our results revealed that both interference cost on a verbal memory task and relational memory task performance were significantly related to cornu ammonis 1-2 (CA1-CA2) stiffness (p = 0.018 and p = 0.011, respectively), with CA1-CA2 stiffness significantly mediating the relationship between age and interference cost performance (p = 0.031). There were also significant associations between delayed free verbal recall performance and stiffness of both the dentate gyrus-cornu ammonis 3 (DG-CA3; p = 0.016) and subiculum (SUB; p = 0.032) regions. This further exemplifies the functional specialization of HCsf in declarative memory and the potential use of MRE measures as clinical biomarkers in assessing brain health in aging and disease.SIGNIFICANCE STATEMENT Hippocampal subfields are cytoarchitecturally unique structures involved in distinct aspects of memory processing. Magnetic resonance elastography is a technique that can noninvasively image tissue viscoelastic mechanical properties, potentially serving as sensitive biomarkers of aging and neurodegeneration related to functional outcomes. High-resolution in vivo imaging has invigorated interest in determining subfield functional specialization and their differential vulnerability in aging and disease. Applying MRE to probe subfield-specific cognitive correlates will indicate that measures of subfield stiffness can determine the integrity of structures supporting specific domains of memory performance. These findings will further validate our high-resolution MRE method and support the potential use of subfield stiffness measures as clinical biomarkers in classifying aging and disease states.

OSCILLATE: A low-rank approach for accelerated magnetic resonance elastography.

PURPOSE: MR elastography (MRE) is a technique to characterize brain mechanical properties in vivo. Due to the need to capture tissue deformation in multiple directions over time, MRE is an inherently long acquisition, which limits achievable resolution and use in challenging populations. The purpose of this work is to develop a method for accelerating MRE acquisition by using low-rank image reconstruction to exploit inherent spatiotemporal correlations in MRE data. THEORY AND METHODS: The proposed MRE sampling and reconstruction method, OSCILLATE (Observing Spatiotemporal Correlations for Imaging with Low-rank Leveraged Acceleration in Turbo Elastography), involves alternating which k-space points are sampled between each repetition by a reduction factor, ROSC. Using a predetermined temporal basis from a low-resolution navigator in a joint low-rank image reconstruction, all images can be accurately reconstructed from a reduced amount of k-space data. RESULTS: Decomposition of MRE displacement data demonstrated that, on average, 96.1% of all energy from an MRE dataset is captured at rank L = 12 (reduced from a full rank of 24). Retrospectively undersampling data with ROSC  = 2 and reconstructing at low-rank (L = 12) yields highly accurate stiffness maps with voxel-wise error of 5.8% ± 0.7%. Prospectively undersampled data at ROSC  = 2 were successfully reconstructed without loss of material property map fidelity, with average global stiffness error of 1.0% ± 0.7% compared to fully sampled data. CONCLUSIONS: OSCILLATE produces whole-brain MRE data at 2 mm isotropic resolution in 1 min 48 s.

Evaluation of cerebral cortex viscoelastic property estimation with nonlinear inversion magnetic resonance elastography.

Objective. Magnetic resonance elastography (MRE) of the brain has shown promise as a sensitive neuroimaging biomarker for neurodegenerative disorders; however, the accuracy of performing MRE of the cerebral cortex warrants investigation due to the unique challenges of studying thinner and more complex geometries.Approach. A series of realistic, whole-brain simulation experiments are performed to examine the accuracy of MRE to measure the viscoelasticity (shear stiffness,µ, and damping ratio, ξ) of cortical structures predominantly effected in aging and neurodegeneration. Variations to MRE spatial resolution and the regularization of a nonlinear inversion (NLI) approach are examined.Main results. Higher-resolution MRE displacement data (1.25 mm isotropic resolution) and NLI with a low soft prior regularization weighting provided minimal measurement error compared to other studied protocols. With the optimized protocol, an average error inµand ξ was 3% and 11%, respectively, when compared with the known ground truth. Mid-line structures, as opposed to those on the cortical surface, generally display greater error. Varying model boundary conditions and reducing the thickness of the cortex by up to 0.67 mm (which is a realistic portrayal of neurodegenerative pathology) results in no loss in reconstruction accuracy.Significance. These experiments establish quantitative guidelines for the accuracy expected ofin vivoMRE of the cortex, with the proposed method providing valid MRE measures for future investigations into cortical viscoelasticity and relationships with health, cognition, and behavior.

Correlated noise in brain magnetic resonance elastography.

PURPOSE: Magnetic resonance elastography (MRE) uses phase-contrast MRI to generate mechanical property maps of the in vivo brain through imaging of tissue deformation from induced mechanical vibration. The mechanical property estimation process in MRE can be susceptible to noise from physiological and mechanical sources encoded in the phase, which is expected to be highly correlated. This correlated noise has yet to be characterized in brain MRE, and its effects on mechanical property estimates computed using inversion algorithms are undetermined. METHODS: To characterize the effects of signal noise in MRE, we conducted 3 experiments quantifying (1) physiomechanical sources of signal noise, (2) physiological noise because of cardiac-induced movement, and (3) impact of correlated noise on mechanical property estimates. We use a correlation length metric to estimate the extent that correlated signal persists in MRE images and demonstrate the effect of correlated noise on property estimates through simulations. RESULTS: We found that both physiological noise and vibration noise were greater than image noise and were spatially correlated across all subjects. Added physiological and vibration noise to simulated data resulted in property maps with higher error than equivalent levels of Gaussian noise. CONCLUSION: Our work provides the foundation to understand contributors to brain MRE data quality and provides recommendations for future work to correct for signal noise in MRE.

Quantitative effects of off-resonance related distortion on brain mechanical property estimation with magnetic resonance elastography.

Off-resonance related geometric distortion can impact quantitative MRI techniques, such as magnetic resonance elastography (MRE), and result in errors to these otherwise sensitive metrics of brain health. MRE is a phase contrast technique to determine the mechanical properties of tissue by imaging shear wave displacements and estimating tissue stiffness through inverse solution of Navier's equation. In this study, we systematically examined the quantitative effects of distortion and corresponding correction approaches on MRE measurements through a series of simulations, phantom models, and in vivo brain experiments. We studied two different k-space trajectories, echo-planar imaging and spiral, and we determined that readout time, off-resonance gradient strength, and the combination of readout direction and off-resonance gradient direction, impact the estimated mechanical properties. Images were also processed through traditional distortion correction pipelines, and we found that each of the correction mechanisms works well for reducing stiffness errors, but are limited in cases of very large distortion. The ability of MRE to detect subtle changes to neural tissue health relies on accurate, artifact-free imaging, and thus off-resonance related geometric distortion must be considered when designing sequences and protocols by limiting readout time and applying correction where appropriate.

Aging brain mechanics: Progress and promise of magnetic resonance elastography.

Neuroimaging techniques that can sensitivity characterize healthy brain aging and detect subtle neuropathologies have enormous potential to assist in the early detection of neurodegenerative conditions such as Alzheimer's disease. Magnetic resonance elastography (MRE) has recently emerged as a reliable, high-resolution, and especially sensitive technique that can noninvasively characterize tissue biomechanical properties (i.e., viscoelasticity) in vivo in the living human brain. Brain tissue viscoelasticity provides a unique biophysical signature of neuroanatomy that are representative of the composition and organization of the complex tissue microstructure. In this article, we detail how progress in brain MRE technology has provided unique insights into healthy brain aging, neurodegeneration, and structure-function relationships. We further discuss additional promising technical innovations that will enhance the specificity and sensitivity for brain MRE to reveal considerably more about brain aging as well as its potentially valuable role as an imaging biomarker of neurodegeneration. MRE sensitivity may be particularly useful for assessing the efficacy of rehabilitation strategies, assisting in differentiating between dementia subtypes, and in understanding the causal mechanisms of disease which may lead to eventual pharmacotherapeutic development.

An analytical model of full-field displacement and strain induced by amplitude-modulated focused ultrasound in harmonic motion imaging.

The majority of disease processes involves changes in the micro-structure of the affected tissue, which can translate to changes in the mechanical properties of the corresponding tissue. Harmonic motion imaging (HMI) is an elasticity imaging technique that allows the study of the mechanical parameters of tissue by detecting the tissue response by a harmonic motion field, which is generated by oscillatory acoustic radiation force. HMI has been demonstrated in tumor detection and characterization as well as monitoring of ablation procedures. In this study, an analytical HMI model is demonstrated and compared with a finite element model (FEM), allowing rapid and accurate computation of the displacement, strain, and shear wave velocity (SWV) at any location in a homogenous linear elastic material. Average absolute differences between the analytical model and the FEM were respectively 1.2% for the displacements and 0.5% for the strains for 41 940 force voxels at 0.22 s per displacement evaluation. A convergence study showed that the average difference could be further decreased to 1.0% and 0.15% for the displacements and strains, respectively, if force resolution is increased. SWV fields, as calculated with the FEM and the analytical model, have regional differences in velocities up to 0.57 m s-1with an average absolute difference of 0.11 ± 0.07 m s-1, primarily due to imperfections in the non-reflecting FEM boundary conditions. The apparent SWV differed from the commonly used plane-wave approximation by up to 1.2 m s-1due to near and intermediate field effects. Maximum displacement amplitudes for a model with an inclusion stabilize within 10% of the homogenous model at an inclusion radius of 10 mm while the maximum strain reacts faster, stabilizing at an inclusion radius of 3 mm. In conclusion, an analytical model for HMI stiffness estimation is presented in this paper. The analytical model has advantages over FEM as the full-field displacements do not need to be calculated to evaluate the model at a single measurement point. This advantage, together with the computational speed, makes the analytical model useful for real-time imaging applications. However, the analytical model was found to have restrictive assumptions on tissue homogeneity and infinite dimensions, while the FEM approaches were shown adaptable to variable geometry and non-homogenous properties.

Effect of Aging on the Viscoelastic Properties of Hippocampal Subfields Assessed with High-Resolution MR Elastography.

Age-related memory impairments have been linked to differences in structural brain parameters, including the integrity of the hippocampus (HC) and its distinct hippocampal subfields (HCsf). Imaging methods sensitive to the underlying tissue microstructure are valuable in characterizing age-related HCsf structural changes that may relate to cognitive function. Magnetic resonance elastography (MRE) is a noninvasive MRI technique that can quantify tissue viscoelasticity and may provide additional information about aging effects on HCsf health. Here, we report a high-resolution MRE protocol to quantify HCsf viscoelasticity through shear stiffness, µ, and damping ratio, ξ, which reflect the integrity of tissue composition and organization. HCsf exhibit distinct mechanical properties-the subiculum had the lowest µ and both subiculum and entorhinal cortex had the lowest ξ. Both measures correlated with age: HCsf µ was lower with age (P < 0.001) whereas ξ was higher (P = 0.002). The magnitude of age-related differences in ξ varied across HCsf (P = 0.011), suggesting differential patterns of brain aging. This study demonstrates the feasibility of using MRE to assess HCsf microstructural integrity and suggests incorporation of these metrics to evaluate HC health in neurocognitive disorders.

Poroelasticity as a Model of Soft Tissue Structure: Hydraulic Permeability Reconstruction for Magnetic Resonance Elastography in Silico.

Magnetic Resonance Elastography allows noninvasive visualization of tissue mechanical properties by measuring the displacements resulting from applied stresses, and fitting a mechanical model. Poroelasticity naturally lends itself to describing tissue - a biphasic medium, consisting of both solid and fluid components. This article reviews the theory of poroelasticity, and shows that the spatial distribution of hydraulic permeability, the ease with which the solid matrix permits the flow of fluid under a pressure gradient, can be faithfully reconstructed without spatial priors in simulated environments. The paper describes an in-house MRE computational platform - a multi-mesh, finite element poroelastic solver coupled to an artificial epistemic agent capable of running Bayesian inference to reconstruct inhomogenous model mechanical property images from measured displacement fields. Building on prior work, the domain of convergence for inference is explored, showing that hydraulic permeabilities over several orders of magnitude can be reconstructed given very little prior knowledge of the true spatial distribution.