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.

Scatter-based magnetic resonance elastography.

Elasticity is a sensitive measure of the microstructural constitution of soft biological tissues and increasingly used in diagnostic imaging. Magnetic resonance elastography (MRE) uniquely allows in vivo measurement of the shear elasticity of brain tissue. However, the spatial resolution of MRE is inherently limited as the transformation of shear wave patterns into elasticity maps requires the solution of inverse problems. Therefore, an MRE method is introduced that avoids inversion and instead exploits shear wave scattering at elastic interfaces between anatomical regions of different shear compliance. This compliance-weighted imaging (CWI) method can be used to evaluate the mechanical consistency of cerebral lesions or to measure relative stiffness differences between anatomical subregions of the brain. It is demonstrated that CWI-MRE is sensitive enough to reveal significant elasticity variations within inner brain parenchyma: the caudate nucleus (head) was stiffer than the lentiform nucleus and the thalamus by factors of 1.3 +/- 0.1 and 1.7 +/- 0.2, respectively (P < 0.001). CWI-MRE provides a unique method for characterizing brain tissue by identifying local stiffness variations.

The impact of aging and gender on brain viscoelasticity.

Viscoelasticity is a sensitive measure of the microstructural constitution of soft biological tissue and is increasingly used as a diagnostic marker, e.g. in staging liver fibrosis or characterizing breast tumors. In this study, multifrequency magnetic resonance elastography was used to investigate the in vivo viscoelasticity of healthy human brain in 55 volunteers (23 females) ranging in age from 18 to 88 years. The application of four vibration frequencies in an acoustic range from 25 to 62.5 Hz revealed for the first time how physiological aging changes the global viscosity and elasticity of the brain. Using the rheological springpot model, viscosity and elasticity are combined in a parameter mu that describes the solid-fluid behavior of the tissue and a parameter alpha related to the tissue's microstructure. It is shown that the healthy adult brain undergoes steady parenchymal 'liquefaction' characterized by a continuous decline in mu of 0.8% per year (P<0.001), whereas alpha remains unchanged. Furthermore, significant sex differences were found with female brains being on average 9% more solid-like than their male counterparts rendering women more than a decade 'younger' than men with respect to brain mechanics (P=0.016). These results set the background for using cerebral multifrequency elastography in diagnosing subtle neurodegenerative processes not detectable by other diagnostic methods.

Cardiac magnetic resonance elastography. Initial results.

OBJECTIVES: To develop cardiac magnetic resonance elastography (MRE) for noninvasively measuring left ventricular (LV) pressure-volume (P-V) work. MATERIAL AND METHODS: The anterior chest wall of 8 healthy volunteers was vibrated by 24.3-Hz acoustic waves for stimulating oscillating shear deformation in myocardium and adjacent blood. The induced motion was recorded by an electrocardiogram-gated, vibration-synchronized and segmented gradient-recalled echo MRE sequence acquiring 360 phase-contrast wave images with a temporal resolution of 5.16 milliseconds in the short-axis view during controlled breathing. Relative changes in wave amplitudes served as a measure of LV pressure variation during the cardiac cycle. MRE pressure data were combined with LV volumes obtained from segmentation of 3D cine-steady-state free precession data sets. RESULTS: Shear wave amplitudes decreased from diastole to systole, which reflects the dynamics of myocardial shear modulus variations during the cardiac cycle. Assuming spherical shear stress, a linear relationship between myocardial stiffness and LV pressure was derived. The MRE-measured pressure was plotted as a function of LV volumes. Characteristic P-V cycles displayed an isovolumetric increase in pressure during early systole, whereas less pronounced volume conservation was observed in early diastole. Mean cardiac P-V work in all volunteers was 0.85 +/- 0.11 J. CONCLUSION: In vivo cardiac MRE is a noninvasive method for measuring pressure-related heart function determined by shear modulus variations in the LV wall. This is the first noninvasive mechanical test of cardiac work in the human heart and is potentially useful for assessing pathologies associated with increased myocardial stiffness such as diastolic dysfunction.

Assessment of liver viscoelasticity using multifrequency MR elastography.

MR elastography (MRE) allows the noninvasive assessment of the viscoelastic properties of human organs based on the organ response to oscillatory shear stress. Shear waves of a given frequency are mechanically introduced and the propagation is imaged by applying motion-sensitive gradients. An experiment was set up that introduces multifrequency shear waves combined with broadband motion sensitization to extend the dynamic range of MRE from one given frequency to, in this study, four different frequencies. With this approach, multiple wave images corresponding to the four driving frequencies are simultaneously acquired and can be evaluated with regard to the dispersion of the complex modulus over the respective frequency. A viscoelastic model based on two shear moduli and one viscosity parameter was used to reproduce the experimental wave speed and wave damping dispersion. The technique was applied in eight healthy volunteers and eight patients with biopsy-proven high-grade liver fibrosis (grade 3-4). Fibrotic liver had a significantly higher (P < 0.01) viscosity (14.4 +/- 6.6 Pa x s) and elastic moduli (2.91 +/- 0.84 kPa; 4.83 +/- 1.77 kPa) than the viscosity (7.3 +/- 2.3 Pa x s) and elastic moduli (1.16 +/- 0.28 kPa; 1.97 +/- 0.30 kPa) of normal volunteers. Multifrequency MRE is well suited for the noninvasive differentiation of normal and fibrotic liver as it allows the measurement of rheologic material properties.

Non-invasive measurement of brain viscoelasticity using magnetic resonance elastography.

The purpose of this work was to develop magnetic resonance elastography (MRE) for the fast and reproducible measurement of spatially averaged viscoelastic constants of living human brain. The technique was based on a phase-sensitive echo planar imaging acquisition. Motion encoding was orthogonal to the image plane and synchronized to intracranial shear vibrations at driving frequencies of 25 and 50 Hz induced by a head-rocker actuator. Ten time-resolved phase-difference wave images were recorded within 60 s and analyzed for shear stiffness and shear viscosity. Six healthy volunteers (six men; mean age 34.5 years; age range 25-44 years) underwent 23-39 follow-up MRE studies over a period of 6 months. Interindividual mean +/- SD shear moduli and shear viscosities were found to be 1.17 +/- 0.03 kPa and 3.1 +/- 0.4 Pas for 25 Hz and 1.56 +/- 0.07 kPa and 3.4 +/- 0.2 Pas for 50 Hz, respectively (P < or = 0.01). The intraindividual range of shear modulus data was 1.01-1.31 kPa (25 Hz) and 1.33-1.77 kPa (50 Hz). The observed modulus dispersion indicates a limited applicability of Voigt's model to explain viscoelastic behavior of brain parenchyma within the applied frequency range. The narrow distribution of data within small confidence intervals demonstrates excellent reproducibility of the experimental protocol. The results are necessary as reference data for future comparisons between healthy and pathological human brain viscoelastic data.

Noninvasive assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity.

MR elastography (MRE) enables the noninvasive determination of the viscoelastic behavior of human internal organs based on their response to oscillatory shear stress. An experiment was developed that combines multifrequency shear wave actuation with broad-band motion sensitization to extend the dynamic range of a single MRE examination. With this strategy, multiple wave images corresponding to different driving frequencies are simultaneously received and can be analyzed by evaluating the dispersion of the complex modulus over frequency. The technique was applied on the brain and liver of five healthy volunteers. Its repeatability was tested by four follow-up studies in each volunteer. Five standard rheological models (Maxwell, Voigt, Zener, Jeffreys and fractional Zener model) were assessed for their ability to reproduce the observed dispersion curves. The three-parameter Zener model was found to yield the most consistent results with two shear moduli mu(1) = 0.84 +/- 0.22 (1.36 +/- 0.31) kPa, mu(2) = 2.03 +/- 0.19 (1.86 +/- 0.34) kPa and one shear viscosity of eta = 6.7 +/- 1.3 (5.5 +/- 1.6) Pa s (interindividual mean +/- SD) in brain (liver) experiments. Significant differences between the rheological parameters of brain and liver were found for mu(1) and eta (P < 0.05), indicating that human brain is softer and possesses a higher viscosity than liver.

Two-dimensional waveform analysis in MR elastography of skeletal muscles.

A method for direct determination of anisotropic elastic coefficients using two-dimensional shear wave patterns is introduced. Thereby, the symmetry of the wave patterns is approximated by a squared elliptic equation yielding an explicit relation between waveform and elasticity. The method is used to analyse MR elastography wave images of the biceps acquired by a continuous harmonic excitation at the distal tendon of the muscle. Typically V-shaped wave patterns were observed in this type of tissue, which could be well reproduced by the proposed elliptic approximation of the waveform assuming incompressibility and a transverse isotropic model of elasticity. Without additional experiments, the analysis of straightness, slope and interferences of the wave fronts enabled us to deduce two Young's moduli and one shear modulus, which fully describe the anisotropy of the elasticity of muscles. The results suggest strong anisotropy of the living human biceps causing a shear wave speed parallel to the muscle fibres that is approximately four times faster than the perpendicular shear wave speed.

B-waves in cerebral and spinal cerebrospinal fluid pulsation measurement by magnetic resonance imaging.

OBJECTIVE: Noninvasive measurement of B-waves is possible by magnetic resonance (MR) imaging using echo planar imaging (EPI) sequences. In this study, the proportion of B-waves in the cerebrospinal fluid (CSF) of the spinal canal and in the aqueductus cerebri was evaluated under normal and pathologic conditions, respectively. The proportion of the influence of pulse and respiration on the CSF pulsations was estimated. METHODS: The spinal CSF was evaluated in 7 volunteers at 5 spinal levels (C1, C2/3, C 6/7, T5, and T12). Examination of the CSF frequencies at the aqueduct was performed in 14 volunteers, 10 patients with normal pressure hydrocephalus, and 5 patients with an aqueductal stenosis. An EPI sequence was applied at 1.5 T. During the 8-minute measurement time, pulse and respiration were coregistered. A MATLAB routine analyzed the spectral portion of the B-waves and the pulse- and respiration-dependent frequencies of the CSF. RESULTS: The amount of B-waves was small in cerebral (2.5%) and spinal measurements (3.4%) but significantly higher in the spinal CSF (P < 0.001). There was no statistically different amount of B-waves in the aqueduct for volunteers and hydrocephalic patients and between the different spinal levels in healthy volunteers. Spinal measurements revealed a rising portion of respiration-related frequencies from C1 to T12, whereas the portion of pulse-related frequencies declined. CONCLUSIONS: The data support that B-waves are a physiologic phenomenon. They can be delineated in the spinal and cerebral CSF. A higher amount of spinal B-waves reflects a stronger venous and respiratory influence.