Jürgen Braun

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 · s) and elastic moduli (2.91 ± 0.84 kPa; 4.83 ± 1.77 kPa) than the viscosity (7.3 ± 2.3 Pa · 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. Magn Reson Med 60:373–379, 2008.

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.

Fractional encoding of harmonic motions in MR elastography

In MR elastography (MRE) shear waves are magnetically encoded by bipolar gradients that usually oscillate with the same frequency fv as the mechanical vibration. As a result, both the repetition time (TR) and echo time (TE) of such an MRE sequence are greater than the vibration period 1/fv. This causes long acquisition times and considerable signal dephasing in tissue with short transverse relaxation times. Here we propose a reverse concept with TR ≤ 1/fv which we call “fractional” MRE, i.e., only a fraction of one vibration cycle per TR, can be used for motion sensitization. The benefit of fractional MRE is twofold: 1) acquisition times in seconds can be achieved for a single‐phase difference wave image, and 2) materials that combine low elasticity, high viscosity, and short T  2* relaxation times show an increased phase‐to‐noise ratio (PNR). A twofold increase of the phase signal is predicted for liver‐like materials. Volunteer studies performed in liver and biceps show the benefit of fractional MRE. Furthermore, we demonstrate the feasibility of the technique for in vivo myocardial MRE by visualizing transverse wave propagation in the interventricular septum (IVS). Magn Reson Med 57:388–395, 2007.

In vivo viscoelastic properties of the brain in normal pressure hydrocephalus

Nearly half a century after the first report of normal pressure hydrocephalus (NPH), the pathophysiological cause of the disease still remains unclear. Several theories about the cause and development of NPH emphasize disease‐related alterations of the mechanical properties of the brain. MR elastography (MRE) uniquely allows the measurement of viscoelastic constants of the living brain without intervention. In this study, 20 patients (mean age, 69.1 years; nine men, 11 women) with idiopathic (n = 15) and secondary (n = 5) NPH were examined by cerebral multifrequency MRE and compared with 25 healthy volunteers (mean age, 62.1 years; 10 men, 15 women). Viscoelastic constants related to the stiffness (µ) and micromechanical connectivity (α) of brain tissue were derived from the dynamics of storage and loss moduli within the experimentally achieved frequency range of 25–62.5 Hz. In patients with NPH, both storage and loss moduli decreased, corresponding to a softening of brain tissue of about 20% compared with healthy volunteers (p < 0.001). This loss of rigidity was accompanied by a decreasing α parameter (9%, p < 0.001), indicating an alteration in the microstructural connectivity of brain tissue during NPH. This disease‐related decrease in viscoelastic constants was even more pronounced in the periventricular region of the brain. The results demonstrate distinct tissue degradation associated with NPH. Further studies are required to investigate the source of mechanical tissue damage as a potential cause of NPH‐related ventricular expansions and clinical symptoms. Copyright

MR elastography of the human heart: Noninvasive assessment of myocardial elasticity changes by shear wave amplitude variations

Many cardiovascular diseases and disorders are associated with hemodynamic dysfunction. The hearts ability to contract and pump blood through the vascular system primarily depends on the elasticity of the myocardium. This article introduces a magnetic resonance elastography (MRE) technique that allows noninvasive and time‐resolved measurement of changes in myocardial elasticity over the cardiac cycle. To this end, low‐frequency shear vibrations of 24.3 Hz were induced in the human heart via the anterior chest wall. An electrocardiograph (ECG)‐triggered, steady‐state MRE sequence was used to capture shear oscillations with a frame rate of eight images per vibration cycle. The time evolution of 2D‐shear wave fields was observed in two imaging planes through the short axis of the heart in six healthy volunteers. Correlation analysis revealed that wave amplitudes were modulated in synchrony to the heartbeat with up to 2.45 ± 0.18 higher amplitudes during diastole than during systole (interindividual mean ± SD). The reduction of wave amplitudes started at 75 ± 9 ms prior to changes in left ventricular diameter occurring at the beginning of systole. Analysis of this wave amplitude alteration using a linear elastic constitutive model revealed a maximum change in the myocardial wall stiffness of a factor of 37.7 ± 10.6 during the cardiac cycle. Magn Reson Med, 2009.

Shear wave group velocity inversion in MR elastography of human skeletal muscle

In vivo quantification of the anisotropic shear elasticity of soft tissue is an appealing objective of elastography techniques because elastic anisotropy can potentially provide specific information about structural alterations in diseased tissue. Here a method is introduced and applied to MR elastography (MRE) of skeletal muscle. With this method one can elucidate anisotropy by means of two shear moduli (one parallel and one perpendicular to the muscle fiber direction). The technique is based on group velocity inversion applied to bulk shear waves, which is achieved by an automatic analysis of wave‐phase gradients on a spatiotemporal scale. The shear moduli are then accessed by analyzing the directional dependence of the shear wave speed using analytic expressions of group velocities in k‐space, which are numerically mapped to real space. The method is demonstrated by MRE experiments on the biceps muscle of five volunteers, resulting in 5.5 ± 0.9 kPa and 29.3 ± 6.2 kPa (P < 0.05) for the medians of the perpendicular and parallel shear moduli, respectively. The proposed technique combines fast steady‐state free precession (SSFP) MRE experiments and fully automated processing of anisotropic wave data, and is thus an interesting MRI modality for aiding clinical diagnosis. Magn Reson Med, 2006.

Brain Viscoelasticity Alteration in Chronic-Progressive Multiple Sclerosis

Introduction Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE) is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS) is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. Methods We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. Results In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001). Conclusions Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

Viscoelastic properties of liver measured by oscillatory rheometry and multifrequency magnetic resonance elastography

The mechanical properties of liver can sensitively indicate the progression of hepatic fibrosis. Mechanical tissue characterization involves the analysis of the complex shear modulus measured either by oscillatory rheometry or by in vivo elastography. In this study, bovine liver specimens were investigated by oscillatory rheometry and multifrequency magnetic resonance elastography (MRE) in a common frequency range between 25.0 and 62.5 Hz. The results were compared with in vivo MRE of human liver. Storage and loss moduli were quantified, and the data were also analyzed employing a springpot model, yielding a stiffness-related parameter of 2.96+/-0.53 kPa in bovine liver by rheometry and of 2.20+/-0.45 kPa in human liver by in vivo MRE. Furthermore, MRE of excised bovine liver showed that stiffness tended to increase with decreasing sample temperature. In conclusion, mechanical tissue characterization by multifrequency MRE agrees well with oscillatory rheometry, which validates MRE as a method for investigating the rheology of liver tissue.

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. Magn Reson Med, 2012.

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.