Insights and improvements in correspondence between axonal volume fraction measured with diffusion-weighted MRI and electron microscopy.

Biophysical diffusion-weighted imaging (DWI) models are increasingly used in neuroscience to estimate the axonal water fraction ( f AW ), which in turn is key for noninvasive estimation of the axonal volume fraction ( f A ). These models require thorough validation by comparison with a reference method, for example, electron microscopy (EM). While EM studies often neglect the unmyelinated axons and solely report the fraction of myelinated axons, in DWI both myelinated and unmyelinated axons contribute to the DWI signal. However, DWI models often include simplifications, for example, the neglect of differences in the compartmental relaxation times or fixed diffusivities, which in turn might affect the estimation of f AW . We investigate whether linear calibration parameters (scaling and offset) can improve the comparability between EM- and DWI-based metrics of f A . To this end, we (a) used six DWI models based on the so-called standard model of white matter (WM), including two models with fixed compartmental diffusivities (e.g., neurite orientation dispersion and density imaging, NODDI) and four models that fitted the compartmental diffusivities (e.g., white matter tract integrity, WMTI), and (b) used a multimodal data set including ex vivo diffusion DWI and EM data in mice with a broad dynamic range of fibre volume metrics. We demonstrated that the offset is associated with the volume fraction of unmyelinated axons and the scaling factor is associated with different compartmental T 2 and can substantially enhance the comparability between EM- and DWI-based metrics of f A . We found that DWI models that fitted compartmental diffusivities provided the most accurate estimates of the EM-based f A . Finally, we introduced a more efficient hybrid calibration approach, where only the offset is estimated but the scaling is fixed to a theoretically predicted value. Using this approach, a similar one-to-one correspondence to EM was achieved for WMTI. The method presented can pave the way for use of validated DWI-based models in clinical research and neuroscience.

Towards a representative reference for MRI-based human axon radius assessment using light microscopy.

Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions.

Biophysically motivated efficient estimation of the spatially isotropic R2* component from a single gradient-recalled echo measurement.

PURPOSE: To propose and validate an efficient method, based on a biophysically motivated signal model, for removing the orientation-dependent part of R2* using a single gradient-recalled echo (GRE) measurement. METHODS: The proposed method utilized a temporal second-order approximation of the hollow-cylinder-fiber model, in which the parameter describing the linear signal decay corresponded to the orientation-independent part of R2* . The estimated parameters were compared to the classical, mono-exponential decay model for R2* in a sample of an ex vivo human optic chiasm (OC). The OC was measured at 16 distinct orientations relative to the external magnetic field using GRE at 7T. To show that the proposed signal model can remove the orientation dependence of R2* , it was compared to the established phenomenological method for separating R2* into orientation-dependent and -independent parts. RESULTS: Using the phenomenological method on the classical signal model, the well-known separation of R2* into orientation-dependent and -independent parts was verified. For the proposed model, no significant orientation dependence in the linear signal decay parameter was observed. CONCLUSIONS: Since the proposed second-order model features orientation-dependent and -independent components at distinct temporal orders, it can be used to remove the orientation dependence of R2* using only a single GRE measurement.

Single-subject independent component analysis-based intensity normalization in non-quantitative multi-modal structural MRI.

Non-quantitative MRI is prone to intersubject intensity variation rendering signal intensity level based analyses limited. Here, we propose a method that fuses non-quantitative routine T1-weighted (T1w), T2w, and T2w fluid-saturated inversion recovery sequences using independent component analysis and validate it on age and sex matched healthy controls. The proposed method leads to consistent and independent components with a significantly reduced coefficient-of-variation across subjects, suggesting potential to serve as automatic intensity normalization and thus to enhance the power of intensity based statistical analyses. To exemplify this, we show that voxelwise statistical testing on single-subject independent components reveals in particular a widespread sex difference in white matter, which was previously shown using, for example, diffusion tensor imaging but unobservable in the native MRI contrasts. In conclusion, our study shows that single-subject independent component analysis can be applied to routine sequences, thereby enhancing comparability in-between subjects. Unlike quantitative MRI, which requires specific sequences during acquisition, our method is applicable to existing MRI data. Hum Brain Mapp 38:3615-3622, 2017. © 2017 Wiley Periodicals, Inc.

Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder.

OBJECTIVES: Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). METHODS: 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. RESULTS: In NMOSD patients, a significant reduction of |G*| was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). CONCLUSIONS: MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. KEY POINTS: • Magnetic resonance elastography reveals diffuse cerebral tissue changes in patients with NMOSD. • Premature tissue softening in NMOSD patients indicates tissue degeneration. • Hypothesis of a widespread cerebral neurodegeneration in form of diffuse tissue alteration.

Afferent Visual Pathway Affection in Patients with PMP22 Deletion-Related Hereditary Neuropathy with Liability to Pressure Palsies.

BACKGROUND: The PMP22 gene encodes a protein integral to peripheral myelin. Its deletion leads to hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is not expressed in the adult central nervous system, but previous studies suggest a role in CNS myelin development. The objective of this study was to identify potential structural and functional alterations in the afferent visual system in HNPP patients. METHODS: Twenty HNPP patients and 18 matched healthy controls (HC) were recruited in a cross-sectional study. Participants underwent neurological examination including visual acuity, visual evoked potential (VEP) examination, optical coherence tomography (OCT), and magnetic resonance imaging with calculation of brain atrophy, regarding grey and white matter, and voxel based morphometry (VBM), in addition answered the National Eye Institute's 39-item Visual Functioning Questionnaire (NEI-VFQ). Thirteen patients and 6 HC were additionally examined with magnetic resonance spectroscopy (MRS). RESULTS: All patients had normal visual acuity, but reported reduced peripheral vision in comparison to HC in the NEI-VFQ (p = 0.036). VEP latency was prolonged in patients (P100 = 103.7±5.7 ms) in comparison to healthy subjects (P100 = 99.7±4.2 ms, p = 0.007). In OCT, peripapillary retinal nerve fiber layer thickness RNFL was decreased in the nasal sector (90.0±15.5 vs. 101.8±16.5, p = 0.013), and lower nasal sector RNFL correlated with prolonged VEP latency (Rho = -0.405, p = 0.012). MRS revealed reduced tNAA (731.4±45.4 vs. 814.9±62.1, p = 0.017) and tCr (373.8±22.2 vs. 418.7±31.1, p = 0.002) in the visual cortex in patients vs. HC. Whole brain volume, grey and white matter volume, VBM and metabolites in a MRS sensory cortex control voxel did not differ significantly between patients and HC. CONCLUSION: PMP22 deletion leads to functional, metabolic and macro-structural alterations in the afferent visual system of HNPP patients. Our data suggest a functional relevance of these changes for peripheral vision, which warrants further investigation and confirmation.

Higher-resolution MR elastography reveals early mechanical signatures of neuroinflammation in patients with clinically isolated syndrome.

PURPOSE: To assess if higher-resolution magnetic resonance elastography (MRE) is a technique that can measure the in vivo mechanical properties of brain tissue and is sensitive to early signatures of brain tissue degradation in patients with clinically isolated syndrome (CIS). MATERIALS AND METHODS: Seventeen patients with CIS and 33 controls were investigated by MRE with a 3T MRI scanner. Full-wave field data were acquired at seven drive frequencies from 30 to 60 Hz. The spatially resolved higher-resolution maps of magnitude |G*| and phase angle φ of the complex-valued shear modulus were obtained in addition to springpot model parameters. These parameters were spatially averaged in white matter (WM) and whole-brain regions and correlated with clinical and radiological parameters. RESULTS: Spatially resolved MRE revealed that CIS reduced WM viscoelasticity, independent of imaging markers of multiple sclerosis and clinical scores. |G*| was reduced by 14% in CIS (1.4 ± 0.2 kPa vs. 1.7 ± 0.2 kPa, P < 0.001, 95% confidence interval [CI] [-0.4, -0.1] kPa), while φ (0.66 ± 0.04 vs. 0.67 ± 0.04, P = 0.65, 95% CI [-0.04, 0.02]) remained unaltered. Springpot-based shear elasticity showed only a trend of CIS-related reduction (3.4 ± 0.5 kPa vs. 3.7 ± 0.5 kPa, P = 0.06, 95% CI [-0.6, 0.02] kPa) in the whole brain. CONCLUSION: We demonstrate that CIS leads to significantly reduced elasticity of brain parenchyma, raising the prospect of using MRE as an imaging marker for subtle and diffuse tissue damage in neuroinflammatory diseases. J. Magn. Reson. Imaging 2016;44:51-58.

Cerebral multifrequency MR elastography by remote excitation of intracranial shear waves.

The aim of this study was to introduce remote wave excitation for high-resolution cerebral multifrequency MR elastography (mMRE). mMRE of 25-45-Hz drive frequencies by head rocker stimulation was compared with mMRE by remote wave excitation based on a thorax mat in 12 healthy volunteers. Maps of the magnitude |G*| and phase φ of the complex shear modulus were reconstructed using multifrequency dual elasto-visco (MDEV) inversion. After the scan, the subjects and three operators assessed the comfort and convenience of cerebral mMRE using two methods of stimulating the brain. Images were acquired in a coronal view in order to identify anatomical regions along the spinothalamic pathway. In mMRE by remote actuation, all subjects and operators appreciated an increased comfort and simplified procedural set-up. The resulting strain amplitudes in the brain were sufficiently large to analyze using MDEV inversion, and yielded high-resolution viscoelasticity maps which revealed specific anatomical details of brain mechanical properties: |G*| was lowest in the pons (0.97 ± 0.08 kPa) and decreased within the corticospinal tract in the caudal-cranial direction from the crus cerebri (1.64 ± 0.26 kPa) to the capsula interna (1.29 ± 0.14 kPa). By avoiding onerous mechanical stimulation of the head, remote excitation of intracranial shear waves can be used to measure viscoelastic parameters of the brain with high spatial resolution. Therewith, the new mMRE method is suitable for neuroradiological examinations in the clinic.

Cerebellar neurochemical alterations in spinocerebellar ataxia type 14 appear to include glutathione deficiency.

Autosomal dominant ataxia type 14 (SCA14) is a rare usually adult-onset progressive disorder with cerebellar neurodegeneration caused by mutations in protein kinase C gamma. We set out to examine cerebellar and extracerebellar neurochemical changes in SCA14 by MR spectroscopy. In 13 SCA14 patients and 13 healthy sex- and age-matched controls, 3-T single-voxel brain proton MR spectroscopy was performed in a cerebellar voxel of interest (VOI) at TE = 30 ms to obtain a neurochemical profile of metabolites with short relaxation times. In the cerebellum and in additional VOIs in the prefrontal cortex, motor cortex, and somatosensory cortex, a second measurement was performed at TE = 144 ms to mainly extract the total N-acetyl-aspartate (tNAA) signal besides the signals for total creatine (tCr) and total choline (tCho). The cerebellar neurochemical profile revealed a decrease in glutathione (6.12E-06 ± 2.50E-06 versus 8.91E-06 ± 3.03E-06; p = 0028) and tNAA (3.78E-05 ± 5.67E-06 versus 4.25E-05 ± 5.15E-06; p = 0023) and a trend for reduced glutamate (2.63E-05 ± 6.48E-06 versus 3.15E-05 ± 7.61E-06; p = 0062) in SCA14 compared to controls. In the tNAA-focused measurement, cerebellar tNAA (296.6 ± 42.6 versus 351.7 ± 16.5; p = 0004) and tCr (272.1 ± 25.2 versus 303.2 ± 31.4; p = 0004) were reduced, while the prefrontal, somatosensory and motor cortex remained unaffected compared to controls. Neuronal pathology in SCA14 detected by MR spectroscopy was restricted to the cerebellum and did not comprise cortical regions. In the cerebellum, we found in addition to signs of neurodegeneration a glutathione reduction, which has been associated with cellular damage by oxidative stress in other neurodegenerative diseases such as Parkinson's disease and Friedreich's ataxia.

MR elastography of the liver and the spleen using a piezoelectric driver, single-shot wave-field acquisition, and multifrequency dual parameter reconstruction.

PURPOSE: Viscoelastic properties of the liver are sensitive to fibrosis. This study proposes several modifications to existing magnetic resonance elastography (MRE) techniques to improve the accuracy of abdominal MRE. METHODS: The proposed method comprises the following steps: (i) wave generation by a nonmagnetic, piezoelectric driver suitable for integration into the patient table, (ii) fast single-shot 3D wave-field acquisition at four drive frequencies between 30 and 60 Hz, and (iii) single-step postprocessing by a novel multifrequency dual parameter inversion of the wave equation. The method is tested in phantoms, healthy volunteers, and patients with portal hypertension and ascites. RESULTS: Spatial maps of magnitude and phase of the complex shear modulus were acquired within 6-8 min. These maps are not subject to bias from inversion-related artifacts known from classic MRE. The spatially averaged modulus for healthy liver was 1.44 ± 0.23 kPa with ϕ = 0.492 ± 0.064. Both parameters were significantly higher in the spleen (2.29 ± 0.97 kPa, P = 0.015 and 0.749 ± 0.144, P = 6.58·10(-5) , respectively). CONCLUSION: The proposed method provides abdominal images of viscoelasticity in a short time with spatial resolution comparable to conventional MR images and improved quality without being compromised by ascites. The new setup allows for the integration of abdominal MRE into the clinical workflow.

High-resolution mechanical imaging of the human brain by three-dimensional multifrequency magnetic resonance elastography at 7T.

Magnetic resonance elastography (MRE) is capable of measuring the viscoelastic properties of brain tissue in vivo. However, MRE is still limited in providing high-resolution maps of mechanical constants. We therefore introduce 3D multifrequency MRE (3DMMRE) at 7T magnetic field strength combined with enhanced multifrequency dual elasto-visco (MDEV) inversion in order to achieve high-resolution elastographic maps of in vivo brain tissue with 1mm(3) resolution. As demonstrated by phantom data, the new MDEV-inversion method provides two high resolution parameter maps of the magnitude (|G*|) and the phase angle (ϕ) of the complex shear modulus. MDEV inversion applied to cerebral 7T-3DMMRE data of five healthy volunteers revealed structures of brain tissue in greater anatomical details than previous work. The viscoelastic properties of cortical gray matter (GM) and white matter (WM) could be differentiated by significantly lower values of |G*| and ϕ in GM (21% [P<0.01]; 8%, [P<0.01], respectively) suggesting that GM is significantly softer and less viscous than WM. In conclusion, 3DMMRE at ultrahigh magnetic fields and MDEV inversion open a new window into characterizing the mechanical structure of in vivo brain tissue and may aid the detection of various neurological disorders based on their effects to mechanical tissue properties.

Towards an elastographic atlas of brain anatomy.

Cerebral viscoelastic constants can be measured in a noninvasive, image-based way by magnetic resonance elastography (MRE) for the detection of neurological disorders. However, MRE brain maps of viscoelastic constants are still limited by low spatial resolution. Here we introduce three-dimensional multifrequency MRE of the brain combined with a novel reconstruction algorithm based on a model-free multifrequency inversion for calculating spatially resolved viscoelastic parameter maps of the human brain corresponding to the dynamic range of shear oscillations between 30 and 60 Hz. Maps of two viscoelastic parameters, the magnitude and the phase angle of the complex shear modulus, |G*| and φ, were obtained and normalized to group templates of 23 healthy volunteers in the age range of 22 to 72 years. This atlas of the anatomy of brain mechanics reveals a significant contrast in the stiffness parameter |G*| between different anatomical regions such as white matter (WM; 1.252±0.260 kPa), the corpus callosum genu (CCG; 1.104±0.280 kPa), the thalamus (TH; 1.058±0.208 kPa) and the head of the caudate nucleus (HCN; 0.649±0.101 kPa). φ, which is sensitive to the lossy behavior of the tissue, was in the order of CCG (1.011±0.172), TH (1.037±0.173), CN (0.906±0.257) and WM (0.854±0.169). The proposed method provides the first normalized maps of brain viscoelasticity with anatomical details in subcortical regions and provides useful background data for clinical applications of cerebral MRE.

Compression-sensitive magnetic resonance elastography.

Magnetic resonance elastography (MRE) quantifies the shear modulus of biological tissue to detect disease. Complementary to the shear elastic properties of tissue, the compression modulus may be a clinically useful biomarker because it is sensitive to tissue pressure and poromechanical interactions. In this work, we analyze the capability of MRE to measure volumetric strain and the dynamic bulk modulus (P-wave modulus) at a harmonic drive frequency commonly used in shear-wave-based MRE. Gel phantoms with various densities were created by introducing CO2-filled cavities to establish a compressible effective medium. The dependence of the effective medium's bulk modulus on phantom density was investigated via static compression tests, which confirmed theoretical predictions. The P-wave modulus of three compressible phantoms was calculated from volumetric strain measured by 3D wave-field MRE at 50 Hz drive frequency. The results demonstrate the MRE-derived volumetric strain and P-wave modulus to be sensitive to the compression properties of effective media. Since the reconstruction of the P-wave modulus requires third-order derivatives, noise remains critical, and P-wave moduli are systematically underestimated. Focusing on relative changes in the effective bulk modulus of tissue, compression-sensitive MRE may be useful for the noninvasive detection of diseases involving pathological pressure alterations such as hepatic hypertension or hydrocephalus.

Imaging of magnetic microfield distortions allows sensitive single-cell detection.

Cell tracking with magnetic resonance imaging (MRI) is mostly performed using superparamagnetic iron oxide (SPIO) nanoparticle-labeled cells. However, negative contrast in T2*-weighted imaging is inherently problematic as a homogeneous background signal is required to visualize the negative signal. In a magnetic field, SPIO-labeled cells develop their own magnetization, distorting the main field. We show here a method to visualize these distortions and use them to identify single cells with increased sensitivity and certainty compared to T2* images. We labeled HeLa cells with SPIOs, suspended labeled cells in agarose to make phantoms, and performed high-resolution gradient-echo MRI. Phase images were processed to enhance the visibility of single cells. To quantify SPIO content, we generated a map of frequency differences. MRI of cell phantoms showed that single cells could be detected at concentrations ranging from 200 to 10,000 cells mL(-1). Postprocessing of the magnetic resonance phase images reveals characteristic microfield distortions, increasing dramatically the sensitivity of cell recognition, compared to unprocessed T2* images. Calculating frequency shifts and comparing microfield distortions to simulations permit estimation of the nanoparticle load of single cells. We expect the ability to detect and quantify the iron load of single cells to prove useful in studies of cell trafficking, especially in rare cell populations.

Measurement of vibration-induced volumetric strain in the human lung.

Noninvasive image-based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase-contrast MRI to measure three-dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three-dimensional vector fields of 50-Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective-medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression-sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence-sensitive MRI may serve as a noninvasive marker sensitive to disease-related alterations of regional elastic recoil pressure in the lungs.

Fractal network dimension and viscoelastic powerlaw behavior: I. A modeling approach based on a coarse-graining procedure combined with shear oscillatory rheometry.

Recent advances in dynamic elastography and biorheology have revealed that the complex shear modulus, G*, of various biological soft tissues obeys a frequency-dependent powerlaw. This viscoelastic powerlaw behavior implies that mechanical properties are communicated in tissue across the continuum of scales from microscopic to macroscopic. For deriving constitutive constants from the dispersion of G* in a biological tissue, a hierarchical fractal model is introduced that accounts for multiscale networks. Effective-media powerlaw constants are derived by a constitutive law based on cross-linked viscoelastic clusters embedded in a rigid environment. The spatial variation of G* is considered at each level of hierarchy by an iterative coarse-graining procedure. The establishment of cross-links in this model network is associated with an increasing fractal dimension and an increasing viscoelastic powerlaw exponent. This fundamental relationship between shear modulus dynamics and fractal dimension of the mechanical network in tissue is experimentally reproduced in phantoms by applying shear oscillatory rheometry to layers of tangled paper strips embedded in agarose gel. Both model and experiments demonstrate the sensitivity of G* to the density of the mechanical network in tissue, corroborating disease-related alterations of the viscoelastic powerlaw exponent in human parenchyma demonstrated by in vivo elastography.

Multifrequency inversion in magnetic resonance elastography.

Time-harmonic shear wave elastography is capable of measuring viscoelastic parameters in living tissue. However, finite tissue boundaries and waveguide effects give rise to wave interferences which are not accounted for by standard elasticity reconstruction methods. Furthermore, the viscoelasticity of tissue causes dispersion of the complex shear modulus, rendering the recovered moduli frequency dependent. Therefore, we here propose the use of multifrequency wave data from magnetic resonance elastography (MRE) for solving the inverse problem of viscoelasticity reconstruction by an algebraic least-squares solution based on the springpot model. Advantages of the method are twofold: (i) amplitude nulls appearing in single-frequency standing wave patterns are mitigated and (ii) the dispersion of storage and loss modulus with drive frequency is taken into account by the inversion procedure, thereby avoiding subsequent model fitting. As a result, multifrequency inversion produces fewer artifacts in the viscoelastic parameter map than standard single-frequency parameter recovery and may thus support image-based viscoelasticity measurement. The feasibility of the method is demonstrated by simulated wave data and MRE experiments on a phantom and in vivo human brain. Implemented as a clinical method, multifrequency inversion may improve the diagnostic value of time-harmonic MRE in a large variety of applications.

Viscoelasticity-based MR elastography of skeletal muscle.

An in vivo multifrequency magnetic resonance elastography (MRE) protocol was developed for studying the viscoelastic properties of human skeletal muscle in different states of contraction. Low-frequency shear vibrations in the range of 25-62.5 Hz were synchronously induced into the femoral muscles of seven volunteers and measured in a cross-sectional view by encoding the fast-transverse shear wave component parallel to the muscle fibers. The so-called springpot model was used for deriving two viscoelastic constants, µ and α, from the dispersion functions of the complex shear modulus in relaxed and in loaded muscle. Representing the shear elasticity parallel to the muscle fibers, µ increased in all volunteers upon contraction from 2.68 ± 0.23 kPa to 3.87 ± 0.50 kPa. Also α varied with load, indicating a change in the geometry of the mechanical network of muscle from relaxation (α = 0.253 ± 0.009) to contraction (α = 0.270 ± 0.009). These results provide a reference for a future assessment of muscular dysfunction using rheological parameters.

In vivo magnetic resonance elastography of human brain at 7 T and 1.5 T.

PURPOSE: To investigate the feasibility of quantitative in vivo ultrahigh field magnetic resonance elastography (MRE) of the human brain in a broad range of low-frequency mechanical vibrations. MATERIALS AND METHODS: Mechanical vibrations were coupled into the brain of a healthy volunteer using a coil-driven actuator that either oscillated harmonically at single frequencies between 25 and 62.5 Hz or performed a superimposed motion consisting of multiple harmonics. Using a motion sensitive single-shot spin-echo echo planar imaging sequence shear wave displacements in the brain were measured at 1.5 and 7 T in whole-body MR scanners. Spatially averaged complex shear moduli were calculated applying Helmholtz inversion. RESULTS: Viscoelastic properties of brain tissue could be reliably determined in vivo at 1.5 and 7 T using both single-frequency and multifrequency wave excitation. The deduced dispersion of the complex modulus was consistent within different experimental settings of this study for the measured frequency range and agreed well with literature data. CONCLUSION: MRE of the human brain is feasible at 7 T. Superposition of multiple harmonics yields consistent results as compared to standard single-frequency based MRE. As such, MRE is a system-independent modality for measuring the complex shear modulus of in vivo human brain in a wide dynamic range.

MR-elastography reveals degradation of tissue integrity in multiple sclerosis.

In multiple sclerosis (MS), diffuse brain parenchymal damage exceeding focal inflammation is increasingly recognized to be present from the very onset of the disease, and, although occult to conventional imaging techniques, may present a major cause of permanent neurological disability. Subtle tissue alterations significantly influence biomechanical properties given by stiffness and internal friction, that--in more accessible organs than the brain--are traditionally assessed by manual palpation during the clinical exam. The brain, however, is protected from our sense of touch, and thus our current knowledge on cerebral viscoelasticity is very limited. We developed a clinically feasible magnetic resonance elastography setup sensitive to subtle alterations of brain parenchymal biomechanical properties. Investigating 45 MS patients revealed a significant decrease (13%, P<0.001) of cerebral viscoelasticity compared to matched healthy volunteers, indicating a widespread tissue integrity degradation, while structure-geometry defining parameters remained unchanged. Cerebral viscoelasticity may represent a novel in vivo marker of neuroinflammatory and neurodegenerative pathology.