Sebastian Papazoglou

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.

In vivo determination of hepatic stiffness using steady-state free precession magnetic resonance elastography.

Objective:The objective of this study was to introduce an magnetic resonance elastography (MRE) protocol based on fractional motion encoding and planar wave acquisition for rapid measurements of in vivo human liver stiffness. Materials and Methods:Vibrations of a remote actuator membrane were fed by a rigid rod to the patients surface beneath the right costal arch resulting in axial shear deflections of the liver. Data acquisition was performed using a balanced steady-state free precession (bSSFP) sequence incorporating oscillating gradients for motion sensitization. Tissue vibrations of frequency fv = 51 Hz were tuned by twice the sequence repetition time (1/fv = 2TR). Twenty axial images acquired by time-resolved through-plane wave encoding were used for planar elasticity reconstruction. The MRE data acquisition was achieved within 4 breathholds of 17 seconds each. The method was applied to 12 healthy volunteers and 2 patients with diffuse liver disease (fibrosis grade 3). Results:MRE data acquisition was successful in all volunteers and patients. The elastic moduli were measured with values between 1.99 ± 0.16 and 5.77 ± 0.88 kPa. Follow-up studies demonstrated the reproducibility of the method and revealed a difference of 0.74 ± 0.47 kPa (P < 0.05) between the hepatic stiffness of 2 healthy male volunteers. Conclusion:bSSFP combined with fractional MRE enables rapid measurement of liver stiffness in vivo. The used actuation principle supports a 2-dimensional analysis of the strain wave field captured by axial wave images. The measured data indicate individual variations of hepatic stiffness in healthy volunteers.

Algebraic Helmholtz inversion in planar magnetic resonance elastography

Magnetic resonance elastography (MRE) is an increasingly used noninvasive modality for diagnosing diseases using the response of soft tissue to harmonic shear waves. We present a study on the algebraic Helmholtz inversion (AHI) applied to planar MRE, demonstrating that the deduced phase speed of shear waves depends strongly on the relative orientations of actuator polarization, motion encoding direction and image plane as well as on the actuator plate size, signal-to-noise ratio and discretization of the wave image. Results from the numerical calculation of harmonic elastic waves due to different excitation directions and simulated plate sizes are compared to experiments on a gel phantom. The results suggest that correct phase speed can be obtained despite these largely uncontrollable influences, if AHI is based on out-of-plane displacements and the actuator is driven at an optimal frequency yielding an optimal pixel per wavelength resolution in the wave image. Assuming plane waves, the required number of pixels per wavelength depends only on the degree of noise.

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.

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.

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

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.

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.

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.

Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue

Background: Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. Objective: We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. Methods: In 44 patients with relapsing–remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. Results: In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. Conclusion: Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.

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 Youngs 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.