Separation of fluid and solid shear wave fields and quantification of coupling density by magnetic resonance poroelastography.

PURPOSE: Biological soft tissues often have a porous architecture comprising fluid and solid compartments. Upon displacement through physiological or externally induced motion, the relative motion of these compartments depends on poroelastic parameters, such as coupling density ( ρ12 ) and tissue porosity. This study introduces inversion recovery MR elastography (IR-MRE) (1) to quantify porosity defined as fluid volume over total volume, (2) to separate externally induced shear strain fields of fluid and solid compartments, and (3) to quantify coupling density assuming a biphasic behavior of in vivo brain tissue. THEORY AND METHODS: Porosity was measured in eight tofu phantoms and gray matter (GM) and white matter (WM) of 21 healthy volunteers. Porosity of tofu was compared to values obtained by fluid draining and microscopy. Solid and fluid shear-strain amplitudes and ρ12 were estimated both in phantoms and in in vivo brain. RESULTS: T1 -based measurement of tofu porosity agreed well with reference values (R = 0.99, P < .01). Brain tissue porosity was 0.14 ± 0.02 in GM and 0.05 ± 0.01 in WM (P < .001). Fluid shear strain was found to be phase-locked with solid shear strain but had lower amplitudes in both tofu phantoms and brain tissue (P < .05). In accordance with theory, tofu and brain ρ12 were negative. CONCLUSION: IR-MRE allowed for the first time separation of shear strain fields of solid and fluid compartments for measuring coupling density according to the biphasic theory of poroelasticity. Thus, IR-MRE opens horizons for poroelastography-derived imaging markers that can be used in basic research and diagnostic applications.

Inversion-recovery MR elastography of the human brain for improved stiffness quantification near fluid-solid boundaries.

PURPOSE: In vivo MR elastography (MRE) holds promise as a neuroimaging marker. In cerebral MRE, shear waves are introduced into the brain, which also stimulate vibrations in adjacent CSF, resulting in blurring and biased stiffness values near brain surfaces. We here propose inversion-recovery MRE (IR-MRE) to suppress CSF signal and improve stiffness quantification in brain surface areas. METHODS: Inversion-recovery MRE was demonstrated in agar-based phantoms with solid-fluid interfaces and 11 healthy volunteers using 31.25-Hz harmonic vibrations. It was performed by standard single-shot, spin-echo EPI MRE following 2800-ms IR preparation. Wave fields were acquired in 10 axial slices and analyzed for shear wave speed (SWS) as a surrogate marker of tissue stiffness by wavenumber-based multicomponent inversion. RESULTS: Phantom SWS values near fluid interfaces were 7.5 ± 3.0% higher in IR-MRE than MRE (P = .01). In the brain, IR-MRE SNR was 17% lower than in MRE, without influencing parenchymal SWS (MRE: 1.38 ± 0.02 m/s; IR-MRE: 1.39 ± 0.03 m/s; P = .18). The IR-MRE tissue-CSF interfaces appeared sharper, showing 10% higher SWS near brain surfaces (MRE: 1.01 ± 0.03 m/s; IR-MRE: 1.11 ± 0.01 m/s; P < .001) and 39% smaller ventricle sizes than MRE (P < .001). CONCLUSIONS: Our results show that brain MRE is affected by fluid oscillations that can be suppressed by IR-MRE, which improves the depiction of anatomy in stiffness maps and the quantification of stiffness values in brain surface areas. Moreover, we measured similar stiffness values in brain parenchyma with and without fluid suppression, which indicates that shear wavelengths in solid and fluid compartments are identical, consistent with the theory of biphasic poroelastic media.

Tomoelastography of the abdomen: Tissue mechanical properties of the liver, spleen, kidney, and pancreas from single MR elastography scans at different hydration states.

PURPOSE: To develop a compact magnetic resonance elastography (MRE) protocol for abdomen and to investigate the effect of water uptake on tissue stiffness in the liver, spleen, kidney, and pancreas. METHODS: Nine asymptomatic volunteers were investigated by MRE before and after 1 liter water uptake. Shear-wave excitation at four frequencies was transferred to the abdomen from anterior and posterior directions using pressurized air drivers. Tomographic representations of shear-wave speed were produced by analysis of multifrequency wave numbers in axial and coronal images acquired within four breath-holds or under free breathing, respectively. RESULTS: Pre and post water, stiffness of the spleen (pre/post: 2.20 ± 0.10/2.06 ± 0.18 m/s) and kidney (pre/post: 1.93 ± 0.22/1.97 ± 0.23 m/s) was higher than in the liver (pre/post: 1.36 ± 0.10/1.38 ± 0.13 m/s) and pancreas (pre/post: 1.20 ± 0.12/1.20 ± 0.08 m/s), all P < 0.01. Accounting for four drive frequencies, water drinking only changed the splenic stiffness (-6%, P = 0.03), whereas in the frequency range from 50 to 60 Hz the effect became significant also in the pancreas (-6%, P = 0.04) and liver (+3%, P = 0.03). Elastograms of the kidney in coronal view clearly depicted higher stiffness in cortex than in medulla. CONCLUSION: Tomoelastography reveals sensitivity of tissue mechanical properties to the hydration state of multiple abdominal organs within one scan and in unprecedented resolution of anatomical details. Magn Reson Med 78:976-983, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Increasing the spatial resolution and sensitivity of magnetic resonance elastography by correcting for subject motion and susceptibility-induced image distortions.

PURPOSE: To improve the resolution of elasticity maps by adapting motion and distortion correction methods for phase-based magnetic resonance imaging (MRI) contrasts such as magnetic resonance elastography (MRE), a technique for measuring mechanical tissue properties in vivo. MATERIALS AND METHODS: MRE data of the brain were acquired with echo-planar imaging (EPI) at 3T (n = 14) and 7T (n = 18). Motion and distortion correction parameters were estimated using the magnitude images. The real and imaginary part of the complex MRE data were corrected separately and recombined. The width of the point-spread function (PSF) and the position variability were calculated. The images were normalized to the Montreal Neurological Institute (MNI) anatomical template. The gray-to-white matter separability of the elasticity maps was tested. RESULTS: Motion correction sharpened the |G*| maps as demonstrated by a narrowing of the PSF by 0.78 ± 0.51 mm at 7T and 0.52 ± 0.63 mm at 3T. The amount of individual head motion during MRE acquisition correlated with the decrease in the width of the PSF at 7T (r = 0.53, P = 0.025) and at 3T (r = 0.69, P = 0.006) and with the increase of gray-to-white matter separability after motion correction at 7T (r = 0.64, P = 0.0039) and at 3T (r = 0.57, P = 0.0319). Improved spatial accuracy after distortion correction results in a significant increase in separability of gray and white matter stiffness (P = 0.0067), especially in inferior parts of the brain suffering from strong B0 inhomogeneities. CONCLUSION: We demonstrate that our method leads to sharper images and higher spatial accuracy, raising the prospect of the investigation of smaller brain areas with increased sensitivity in studies using MRE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:134-141.

Three-parameter shear wave inversion in MR elastography of incompressible transverse isotropic media: Application to in vivo lower leg muscles.

PURPOSE: To develop and demonstrate MR elastography (MRE) for the measurement of three independent viscoelastic constants of skeletal muscle according to the theory of linear elasticity of incompressible materials with transverse isotropy (TI). METHODS: Three-dimensional multifrequency MRE was applied to soleus, gastrocnemius, and tibialis anterior muscles in 10 healthy volunteers. The rotational wave fields were solved for complex-valued viscoelastic parameters µ12, µ13, and E3 corresponding to two shear moduli (within the planes of isotropy and symmetry of TI materials) and Young's modulus (along the principal fiber axis). RESULTS: Anisotropy was represented by the inequality µ12 < µ13 < 1/3E3 considering storage and loss properties of the soleus and gastrocnemius muscles, whereas storage shear moduli of tibialis were indistinguishable. Storage moduli were: 1.06 ± 0.12, 1.33 ± 0.10, 6.92 ± 0.95 kPa (soleus); 0.90 ± 0.11, 1.30 ± 0.15, 8.22 ± 1.37 kPa (gastrocnemius); 1.26 ± 0.16, 1.27 ± 0.11, 9.29 ± 1.42 kPa (tibialis), for µ12, µ13, and E3, respectively. The muscles were different in their µ12 and E3 values, whereas µ13 was less sensitive to the muscle type. Leg differences were observed in the soleus and gastrocnemius muscles. CONCLUSION: Recovery of the full elasticity tensor in incompressible TI materials is feasible by three-dimensional inversion of the time-harmonic shear wave equation. The method is potentially useful for the clinical evaluation of skeletal muscle anisotropy.

In vivo wideband multifrequency MR elastography of the human brain and liver.

PURPOSE: To demonstrate the feasibility of in vivo wideband MR elastography (wMRE) using continuous, time-harmonic shear vibrations in the frequency range of 10-50 Hz. THEORY AND METHODS: The method was tested in a gel phantom with marked mechanical loss. The brains and livers of eight volunteers were scanned by wMRE using multislice, single-shot MRE with optimized fractional encoding and synchronization of sequence acquisition to vibration. Multifrequency three-dimensional inversion was used to reconstruct compound maps of magnitude |G*| and phase φ of the complex shear modulus. A new phase estimation, φ*, was developed to avoid systematic bias due to noise. RESULTS: In the phantom, G*-dispersion measured by wMRE agreed well with oscillatory shear rheometry. |G*| and φ* measured at vibrations of 10-25 HZ, 25-35 HZ, and 40-50 HZ were 0.62 ± 0.08, 1.56 ± 0.16, 2.18 ± 0.20 kPa and 0.09 ± 0.17, 0.39 ± 0.16, 0.20 ± 0.13 rad in brain and 0.89 ± 0.11, 1.67 ± 0.20, 2.27 ± 0.35 kPa and 0.15 ± 0.10, 0.24 ± 0.05, 0.26 ± 0.05 rad in liver. Elastograms including all frequencies showed the best resolution of anatomical detail with |G*| = 1.38 ± 0.12 kPa, φ* = 0.24 ± 0.10 rad (brain) and |G*| = 1.79 ± 0.23 kPa, φ* = 0.24 ± 0.05 rad (liver). CONCLUSION: wMRE reveals highly dispersive G* properties of the brain and liver, and our results suggest that the influence of large-scale structures such as fluid-filled vessels and sulci on the MRE-measured parameters increases at low vibration frequencies. Magn Reson Med 76:1116-1126, 2016. © 2015 Wiley Periodicals, Inc.

Nonenhanced magnetic resonance angiography (MRA) of the calf arteries at 3 Tesla: intraindividual comparison of 3D flow-dependent subtractive MRA and 2D flow-independent non-subtractive MRA.

PURPOSE: To prospectively compare 3D flow-dependent subtractive MRA vs. 2D flow-independent non-subtractive MRA for assessment of the calf arteries at 3 Tesla. METHODS: Forty-two patients with peripheral arterial occlusive disease underwent nonenhanced MRA of calf arteries at 3 Tesla with 3D flow-dependent subtractive MRA (fast spin echo sequence; 3D-FSE-MRA) and 2D flow-independent non-subtractive MRA (balanced steady-state-free-precession sequence; 2D-bSSFP-MRA). Moreover, all patients underwent contrast-enhanced MRA (CE-MRA) as standard-of-reference. Two readers performed a per-segment evaluation for image quality (4 = excellent to 0 = non-diagnostic) and severity of stenosis. RESULTS: Image quality scores of 2D-bSSFP-MRA were significantly higher compared to 3D-FSE-MRA (medians across readers: 4 vs. 3; p < 0.0001) with lower rates of non-diagnostic vessel segments on 2D-bSSFP-MRA (reader 1: <1 % vs. 15 %; reader 2: 1 % vs. 29 %; p < 0.05). Diagnostic performance of 2D-bSSFP-MRA and 3D-FSE-MRA across readers showed sensitivities of 89 % (214/240) vs. 70 % (168/240), p = 0.0153; specificities: 91 % (840/926) vs. 63 % (585/926), p < 0.0001; and diagnostic accuracies of 90 % (1054/1166) vs. 65 % (753/1166), p < 0.0001. CONCLUSION: 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust nonenhanced MRA technique for assessment of the calf arteries at 3 Tesla with significantly higher image quality and diagnostic accuracy compared to 3D flow-dependent subtractive MRA (3D-FSE-MRA). KEY POINTS: • 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust NE-MRA technique at 3T • 2D-bSSFP-MRA outperforms 3D flow-dependent subtractive MRA (3D-FSE-MRA) as NE-MRA of calf arteries • 2D-bSSFP-MRA is a promising alternative to CE-MRA for calf PAOD evaluation.

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.

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.

In vivo waveguide elastography: effects of neurodegeneration in patients with amyotrophic lateral sclerosis.

PURPOSE: Waveguide elastography (WGE) combines magnetic resonance elastography (MRE), diffusion tensor imaging (DTI), and anisotropic inversions for a determination of the elastic properties of white matter. Previously, the method evaluated the anisotropic elastic properties of the corticospinal tracts (CSTs) of healthy volunteers. Here, the sensitivity of WGE is tested for the detection of pathologic changes in a cohort of patients with Amyotrophic Lateral Sclerosis (ALS). METHODS: MRE and DTI were performed in 14 patients with ALS and 14 healthy, age-matched controls. A comparison was made between three components from WGE and the DTI metrics FA, MD, PD, and RD, for the detection of differences between patients and controls. It was hypothesized that the stiffness values in the CSTs of the patients would be significantly lower due to the known neurodegeneration associated with ALS. RESULTS: Two anisotropic shear moduli polarized parallel and perpendicular to the CSTs were significantly reduced in ALS patients (P < 0.0001), whereas the anisotropic longitudinal modulus polarized parallel to the CSTs showed no significant differences. CONCLUSION: The results of this study suggest a relatively high sensitivity of two anisotropic shear moduli as noninvasive metrics for the assessment of neuronal degeneration within the CSTs.

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.

Towards compression-sensitive magnetic resonance elastography of the liver: sensitivity of harmonic volumetric strain to portal hypertension.

PURPOSE: To assess induced oscillating volumetric strain as a biomarker for intrahepatic blood pressure abnormalities. MATERIALS AND METHODS: Harmonic vibrations of 25 and 50 Hz frequency were induced in the liver and measured by fast 3D vector field magnetic resonance elastography (MRE), followed by processing of the decomposed curl (shear) and divergence (compression) fields. After an initial study on an excised sheep liver, a group of 13 patients with hepatic hypertension were examined before and after implantation of a transjugular intrahepatic portosystemic shunt (TIPS). RESULTS: In the sheep liver specimen, volumetric strain decreased with excess portal pressure, whereas shear strain was not sensitive to portal pressure. In the patient cohort, volumetric strain was significantly higher after TIPS placement (P = 1.38·10(-5) ), while neither shear strain nor the shear modulus were affected. Normalized changes in volumetric strain were significantly correlated with the hepatic venous pressure gradient (R(2) = 0.7258, P = 6.95·10(-5) ) and portal venous pressure (R(2) = 0.5028, P = 0.0016). CONCLUSION: These results indicate for the first time the sensitivity of volumetric strain to symptomatically high values of tissue pressure and motivate further developments in compression-sensitive MRE and poroelastography towards image-based and noninvasive markers of tissue pressure.

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.

In vivo measurement of volumetric strain in the human brain induced by arterial pulsation and harmonic waves.

Motion-sensitive phase contrast magnetic resonance imaging and magnetic resonance elastography are applied for the measurement of volumetric strain and tissue compressibility in human brain. Volumetric strain calculated by the divergence operator using a biphasic effective-medium model is related to dilatation and compression of fluid spaces during harmonic stimulation of the head or during intracranial passage of the arterial pulse wave. In six volunteers, phase contrast magnetic resonance imaging showed that the central cerebrum expands at arterial pulse wave to strain values of (2.8 ± 1.9)·10(-4). The evolution of volumetric strain agrees well with the magnitude of the harmonic divergence measured in eight volunteers by magnetic resonance elastography using external activation of 25 Hz vibration frequency. Intracranial volumetric strain was proven sensitive to venous pressure altered by abdominal muscle contraction. In eight volunteers, an increase in volumetric strain due to abdominal muscle contraction of approximately 45% was observed (P = 0.0001). The corresponding compression modulus in the range of 9.5-13.5 kPa demonstrated that the compressibility of brain tissue at 25 Hz stimulation is much higher than that of water. This pilot study provides the background for compression-sensitive magnetic resonance imaging with or without external head stimulation. Volumetric strain may be sensitive to fluid flow abnormalities or pressure imbalances between vasculature and parenchyma as seen in hydrocephalus.

In vivo waveguide elastography of white matter tracts in the human brain.

White matter is composed primarily of myelinated axons which form fibrous, organized structures and can act as waveguides for the anisotropic propagation of sound. The evaluation of their elastic properties requires both knowledge of the orientation of these waveguides in space, as well as knowledge of the waves propagating along and through them. Here, we present waveguide elastography for the evaluation of the elastic properties of white matter tracts in the human brain, in vivo, using a fusion of diffusion tensor imaging, magnetic resonance elastography, spatial-spectral filtering, a Helmholtz decomposition, and anisotropic inversions, and apply this method to evaluate the material parameters of the corticospinal tracts of five healthy human volunteers. We begin with an Orthotropic inversion model and demonstrate that redundancies in the solution for the nine elastic coefficients indicate that the corticospinal tracts can be approximated by a Hexagonal model (transverse isotropy) comprised of five elastic coefficients representative of a medium with fibers aligned parallel to a central axis, and provides longitudinal and transverse wave velocities on the order of 5.7 m/s and 2.1 m/s, respectively. This method is intended as a new modality to assess white matter structure and health by means of the evaluation of the anisotropic elasticity tensor of nerve fibers.

Vibration-synchronized magnetic resonance imaging for the detection of myocardial elasticity changes.

Vibration synchronized magnetic resonance imaging of harmonically oscillating tissue interfaces is proposed for cardiac magnetic resonance elastography. The new approach exploits cardiac triggered cine imaging synchronized with extrinsic harmonic stimulation (f = 22.83 Hz) to display oscillatory tissue deformations in magnitude images. Oscillations are analyzed by intensity threshold-based image processing to track wave amplitude variations over the cardiac cycle. In agreement to literature data, results in 10 volunteers showed that endocardial wave amplitudes during systole (0.13 ± 0.07 mm) were significantly lower than during diastole (0.34 ± 0.14 mm, P < 0.001). Wave amplitudes were found to decrease 117 ± 40 ms before myocardial contraction and to increase 75 ± 31 ms before myocardial relaxation. Vibration synchronized magnetic resonance imaging improves the temporal resolution of magnetic resonance elastography as it overcomes the use of extra motion encoding gradients, is less sensitive to susceptibility artifacts, and does not suffer from dynamic range constraints frequently encountered in phase-based magnetic resonance elastography.

Simulating Local Deformations in the Human Cortex Due to Blood Flow-Induced Changes in Mechanical Tissue Properties: Impact on Functional Magnetic Resonance Imaging.

Investigating human brain tissue is challenging due to the complexity and the manifold interactions between structures across different scales. Increasing evidence suggests that brain function and microstructural features including biomechanical features are related. More importantly, the relationship between tissue mechanics and its influence on brain imaging results remains poorly understood. As an important example, the study of the brain tissue response to blood flow could have important theoretical and experimental consequences for functional magnetic resonance imaging (fMRI) at high spatial resolutions. Computational simulations, using realistic mechanical models can predict and characterize the brain tissue behavior and give us insights into the consequent potential biases or limitations of in vivo, high-resolution fMRI. In this manuscript, we used a two dimensional biomechanical simulation of an exemplary human gyrus to investigate the relationship between mechanical tissue properties and the respective changes induced by focal blood flow changes. The model is based on the changes in the brain's stiffness and volume due to the vasodilation evoked by neural activity. Modeling an exemplary gyrus from a brain atlas we assessed the influence of different potential mechanisms: (i) a local increase in tissue stiffness (at the level of a single anatomical layer), (ii) an increase in local volume, and (iii) a combination of both effects. Our simulation results showed considerable tissue displacement because of these temporary changes in mechanical properties. We found that the local volume increase causes more deformation and consequently higher displacement of the gyrus. These displacements introduced considerable artifacts in our simulated fMRI measurements. Our results underline the necessity to consider and characterize the tissue displacement which could be responsible for fMRI artifacts.

Viscoelasticity of striatal brain areas reflects variations in body mass index of lean to overweight male adults.

Although a variety of MRI studies investigated the link between body mass index (BMI) and parameters of neural gray matter (GM), the technique applied in most of these studies, voxel-based morphometry (VBM), focusses on the regional GM volume, a macroscopic tissue property. Thus, the studies were not able to exploit the BMI-related information contained in the GM microstructure although PET studies suggest that these factors are important. Here, we used cerebral MR Elastography (MRE) to characterize features of tissue microstructure by evaluating the propagation of shear waves applied to the skull and to assess local tissue viscoelasticity to test the link between this parameter and BMI in 22 lean to overweight males. Unlike the majority of existing MRE studies investigating neural viscoelasticity signals averaged across large brain regions, we used the viscoelasticity of individual voxels for our experiment. Our technique revealed a negative link between BMI and viscoelasticity of two areas of the striatal reward system, i.e., right putamen (t = -8.2; pFWE-corrected = 0.005) and left globus pallidus (t = -7.1; pFWE = 0.037) which was independent of GM volume at these coordinates. Finally, comparison of BMI models based on individual voxels vs. on signals averaged across brain atlas regions demonstrates that voxel-based models explain a significantly higher proportion of variance. Consequently, our findings show that cerebral MRE is suitable to identify medically relevant microstructural tissue properties. Using a voxel-wise analysis approach, we were able to utilize the high spatial resolution of MRE for mapping BMI-related information in the brain.

Cardiac-gated steady-state multifrequency magnetic resonance elastography of the brain: Effect of cerebral arterial pulsation on brain viscoelasticity.

In-vivo brain viscoelasticity measured by magnetic resonance elastography (MRE) is a sensitive imaging marker for long-term biophysical changes in brain tissue due to aging and disease; however, it is still unknown whether MRE can reveal short-term periodic alterations of brain viscoelasticity related to cerebral arterial pulsation (CAP). We developed cardiac-gated steady-state MRE (ssMRE) with spiral readout and stroboscopic sampling of continuously induced mechanical vibrations in the brain at 20, 31.25, and 40 Hz frequencies. Maps of magnitude |G*| and phase ϕ of the complex shear modulus were generated by multifrequency dual visco-elasto inversion with a temporal resolution of 40 ms over 4 s. The method was tested in 12 healthy volunteers. During cerebral systole, |G*| decreased by 6.6 ± 1.9% (56 ± 22 Pa, p < 0.001, mean ± SD), whereas ϕ increased by 0.5 ± 0.5% (0.006 ± 0.005 rad, p = 0.002). The effect size of CAP-induced softening slightly decreased with age by 0.10 ± 0.05% per year (p = 0.04), indicating lower cerebral vascular compliance in older individuals. Our data show for the first time that the brain softens and becomes more viscous during systole, possibly due to an effect of CAP-induced arterial expansion and increased blood volume on effective-medium tissue properties. This sensitivity to vascular-solid tissue interactions makes ssMRE potentially useful for detection of cerebral vascular disease.

Quantitative Multi-Parameter Mapping Optimized for the Clinical Routine.

Using quantitative multi-parameter mapping (MPM), studies can investigate clinically relevant microstructural changes with high reliability over time and across subjects and sites. However, long acquisition times (20 min for the standard 1-mm isotropic protocol) limit its translational potential. This study aimed to evaluate the sensitivity gain of a fast 1.6-mm isotropic MPM protocol including post-processing optimized for longitudinal clinical studies. 6 healthy volunteers (35±7 years old; 3 female) were scanned at 3T to acquire the following whole-brain MPM maps with 1.6 mm isotropic resolution: proton density (PD), magnetization transfer saturation (MT), longitudinal relaxation rate (R1), and transverse relaxation rate (R2*). MPM maps were generated using two RF transmit field (B1+) correction methods: (1) using an acquired B1+ map and (2) using a data-driven approach. Maps were generated with and without Gibb's ringing correction. The intra-/inter-subject coefficient of variation (CoV) of all maps in the gray and white matter, as well as in all anatomical regions of a fine-grained brain atlas, were compared between the different post-processing methods using Student's t-test. The intra-subject stability of the 1.6-mm MPM protocol is 2-3 times higher than for the standard 1-mm sequence and can be achieved in less than half the scan duration. Intra-subject variability for all four maps in white matter ranged from 1.2-5.3% and in gray matter from 1.8 to 9.2%. Bias-field correction using an acquired B1+ map significantly improved intra-subject variability of PD and R1 in the gray (42%) and white matter (54%) and correcting the raw images for the effect of Gibb's ringing further improved intra-subject variability in all maps in the gray (11%) and white matter (10%). Combining Gibb's ringing correction and bias field correction using acquired B1+ maps provides excellent stability of the 7-min MPM sequence with 1.6 mm resolution suitable for the clinical routine.