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.

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.

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.

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.

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.

Transversely-isotropic brain in vivo MR elastography with anisotropic damping.

Measuring tissue parameters from increasingly sophisticated mechanical property models may uncover new contrast mechanisms with clinical utility. Building on previous work on in vivo brain MR elastography (MRE) with a transversely-isotropic with isotropic damping (TI-ID) model, we explore a new transversely-isotropic with anisotropic damping (TI-AD) model that involves six independent parameters describing direction-dependent behavior for both stiffness and damping. The direction of mechanical anisotropy is determined by diffusion tensor imaging and we fit three complex-valued moduli distributions across the full brain volume to minimize differences between measured and modeled displacements. We demonstrate spatially accurate property reconstruction in an idealized shell phantom simulation, as well as an ensemble of 20 realistic, randomly-generated simulated brains. We characterize the simulated precisions of all six parameters across major white matter tracts to be high, suggesting that they can be measured independently with acceptable accuracy from MRE data. Finally, we present in vivo anisotropic damping MRE reconstruction data. We perform t-tests on eight repeated MRE brain exams on a single-subject, and find that the three damping parameters are statistically distinct for most tracts, lobes and the whole brain. We also show that population variations in a 17-subject cohort exceed single-subject measurement repeatability for most tracts, lobes and whole brain, for all six parameters. These results suggest that the TI-AD model offers new information that may support differential diagnosis of brain diseases.

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.

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.

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.

Mapping brain mechanical property maturation from childhood to adulthood.

Magnetic resonance elastography (MRE) is a phase contrast MRI technique which uses external palpation to create maps of brain mechanical properties noninvasively and in vivo. These mechanical properties are sensitive to tissue microstructure and reflect tissue integrity. MRE has been used extensively to study aging and neurodegeneration, and to assess individual cognitive differences in adults, but little is known about mechanical properties of the pediatric brain. Here we use high-resolution MRE imaging in participants of ages ranging from childhood to adulthood to understand brain mechanical properties across brain maturation. We find that brain mechanical properties differ considerably between childhood and adulthood, and that neuroanatomical subregions have differing maturational trajectories. Overall, we observe lower brain stiffness and greater brain damping ratio with increasing age from 5 to 35 years. Gray and white matter change differently during maturation, with larger changes occurring in gray matter for both stiffness and damping ratio. We also found that subregions of cortical and subcortical gray matter change differently, with the caudate and thalamus changing the most with age in both stiffness and damping ratio, while cortical subregions have different relationships with age, even between neighboring regions. Understanding how brain mechanical properties mature using high-resolution MRE will allow for a deeper understanding of the neural substrates supporting brain function at this age and can inform future studies of atypical maturation.

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.

Mapping heterogenous anisotropic tissue mechanical properties with transverse isotropic nonlinear inversion MR elastography.

The white matter tracts of brain tissue consist of highly-aligned, myelinated fibers; white matter is structurally anisotropic and is expected to exhibit anisotropic mechanical behavior. In vivo mechanical properties of tissue can be imaged using magnetic resonance elastography (MRE). MRE can detect and monitor natural and disease processes that affect tissue structure; however, most MRE inversion algorithms assume locally homogenous properties and/or isotropic behavior, which can cause artifacts in white matter regions. A heterogeneous, model-based transverse isotropic implementation of a subzone-based nonlinear inversion (TI-NLI) is demonstrated. TI-NLI reconstructs accurate maps of the shear modulus, damping ratio, shear anisotropy, and tensile anisotropy of in vivo brain tissue using standard MRE motion measurements and fiber directions estimated from diffusion tensor imaging (DTI). TI-NLI accuracy was investigated with using synthetic data in both controlled and realistic settings: excellent quantitative and spatial accuracy was observed and cross-talk between estimated parameters was minimal. Ten repeated, in vivo, MRE scans acquired from a healthy subject were co-registered to demonstrate repeatability of the technique. Good resolution of anatomical structures and bilateral symmetry were evident in MRE images of all mechanical property types. Repeatability was similar to isotropic MRE methods and well within the limits required for clinical success. TI-NLI MRE is a promising new technique for clinical research into anisotropic tissues such as the brain and muscle.

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.

Quantifying stability of parameter estimates forin vivonearly incompressible transversely-isotropic brain MR elastography.

Easily computable quality metrics for measured medical data at point-of-care are important for imaging technologies involving offline reconstruction. Accordingly, we developed a new data quality metric forin vivotransversely-isotropic (TI) magnetic resonance elastography (MRE) based on a generalization of the widely accepted octahedral shear-strain calculation. The metric uses MRE displacement data and an estimate of the TI property field to yield a 'stability map' which predicts regions of low versus high accuracy in the resulting material property reconstructions. We can also calculate an average TI parameter stability (TIPS) score over all voxels in a region of interest for a given measurement to indicate how reliable the recovered mechanical property estimate for the region is expected to be. The calculation is rapid and places little demand on computing resources compared to the computationally intensive material property reconstruction from non-linear inversion (TI-NLI) of displacement fields, making it ideal for point-of-care evaluation of data quality. We test the predictions of the stability map for both simulated phantoms andin vivohuman brain data. We used a range of different displacement datasets from vibrations applied in the anterior-posterior (AP), left-right (LR) and combined AP + LR directions. The TIPS and variability maps (noise sensitivity or variation from the mean of repeated MRE scans) were consistently anti-correlated. Notably, Spearman correlation coefficients ∣R∣>0.6 were found between variability and TIPS score for individual white matter tracts within vivodata. These observations demonstrate the reliability and promise of this data quality metric to screen data rapidly in realistic clinical MRE applications.

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.