Juergen Braun

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.

Viscoelasticity-based Staging of Hepatic Fibrosis with Multifrequency MR Elastography

PURPOSE To analyze the dynamics of the shear modulus of the liver to assess the optimal driving frequency and to determine the diagnostic accuracy of generalized frequency-independent elasticity cutoff values for staging hepatic fibrosis. MATERIALS AND METHODS This institutional review board-approved prospective study included 16 healthy volunteers and 72 patients with biopsy-proved liver fibrosis. After obtaining written informed consent, imaging was performed at 1.5-T by using a motion-sensitized echo-planar imaging sequence. Wave excitation was performed by an actuator introducing a superposition of four frequencies (25.0, 37.5, 50.0, 62.5 Hz) of shear waves. The elasticity µ value and the structure geometry parameter α were calculated by using the two-parameter springpot model. The performance of magnetic resonance (MR) elastography in staging liver fibrosis was assessed with area under the receiver operating characteristic curve (AUROC) analysis and Spearman correlation analysis. RESULTS Elasticity increased with stage of fibrosis, with mean values as follows: for volunteers, 2.25 kPa ± 0.43 (standard deviation); stage F1, 2.61 kPa ± 0.43; stage F2, 3.00 kPa ± 0.63; stage F3, 3.86 kPa ± 0.61; and stage F4, 5.86 kPa ± 1.22. Frequency-independent cutoff values derived for fibrosis and AUROC values, respectively, were as follows: stage F1 or higher, 2.84 kPa and 0.9128; stage F2 or higher, 3.18 kPa and 0.9244; stage F3 or higher, 3.32 kPa and 0.9744; and equivalent to stage F4, 4.21 kPa and 0.9931. The geometry of the tissue (α value) did not correlate with fibrosis. Frequencies of 50.0 Hz and 62.5 Hz displayed the highest diagnostic accuracy. CONCLUSION The diagnostic performance of multifrequency MR elastography in determining the degree of hepatic fibrosis increases with stage of fibrosis. Metrics obtained at the higher frequencies provide better diagnostic performance compared with the lower frequencies. Results of the AUROC analysis demonstrate the high accuracy of frequency-independent cutoff values for staging higher grades of hepatic fibrosis.

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.

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.

Prospective registration of human head magnetic resonance images for reproducible slice positioning using localizer images

To facilitate assessing brain tumor growth and progression of stroke lesions by reproducible slice positioning in human head magnetic resonance (MR) images, a method for prospective registration is proposed that adjusts the image slice position without moving the patient and with no additional scans.

Fractal network dimension and viscoelastic powerlaw behavior: II. An experimental study of structure-mimicking phantoms by magnetic resonance elastography

The dynamics of the complex shear modulus, G*, of soft biological tissue is governed by the rigidity and topology of multiscale mechanical networks. Multifrequency elastography can measure the frequency dependence of G* in soft biological tissue, providing information about the structure of tissue networks at multiple scales. In this study, the viscoelastic properties of structure-mimicking phantoms containing tangled paper stripes embedded in agarose gel are investigated by multifrequency magnetic resonance elastography within the dynamic range of 40–120 Hz. The effective media viscoelastic properties are analyzed in terms of the storage modulus (the real part of G*), the loss modulus (the imaginary part of G*) and the viscoelastic powerlaw given by the two-parameter springpot model. Furthermore, diffusion tensor imaging is used for investigating the effect of network structures on water mobility. The following observations were made: the random paper networks with fractal dimensions between 2.481 and 2.755 had no or minor effects on the storage modulus, whereas the loss modulus was significantly increased about 2.2 kPa per fractal dimension unit (R = 0.962, P < 0.01). This structural sensitivity of the loss modulus was significantly correlated with the springpot powerlaw exponent (0.965, P < 0.01), while for the springpot elasticity modulus, a trend was discernable (0.895, P < 0.05). No effect of the paper network on water diffusion was observed. The gel phantoms with embedded paper stripes presented here are a feasible way for experimentally studying the effect of network topology on soft-tissue viscoelastic parameters. In the dynamic range of in vivo elastography, the fractal network dimension primarily correlates to the loss behavior of soft tissue as can be seen from the loss modulus or the powerlaw exponent of the springpot model. These findings represent the experimental underpinning of structure-sensitive elastography for an improved characterization of various soft-tissue diseases.

Enhanced adult neurogenesis increases brain stiffness: in vivo magnetic resonance elastography in a mouse model of dopamine depletion.

The mechanical network of the brain is a major contributor to neural health and has been recognized by in vivo magnetic resonance elastography (MRE) to be highly responsive to diseases. However, until now only brain softening was observed and no mechanism was known that reverses the common decrement of neural elasticity during aging or disease. We used MRE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model for dopaminergic neurodegeneration as observed in Parkinson’s disease (PD) to study the mechanical response of the brain on adult hippocampal neurogenesis as a robust correlate of neuronal plasticity in healthy and injured brain. We observed a steep transient rise in elasticity within the hippocampal region of up to over 50% six days after MPTP treatment correlating with increased neuronal density in the dentate gyrus, which could not be detected in healthy controls. Our results provide the first indication that new neurons reactively generated following neurodegeneration substantially contribute to the mechanical scaffold of the brain. Diagnostic neuroimaging may thus target on regions of the brain displaying symptomatically elevated elasticity values for the detection of neuronal plasticity following neurodegeneration.

Patient-Activated Three-Dimensional Multifrequency Magnetic Resonance Elastography for High-Resolution Mechanical Imaging of the Liver and Spleen

PURPOSE To introduce a novel in-vivo three-dimensional multifrequency magnetic resonance elastography (3D-MMRE) method for high-resolution mechanical characterization of the liver and spleen. MATERIALS AND METHODS Ten healthy volunteers were examined by abdominal single-shot 3D-MMRE using a novel patient-activated trigger system with respiratory control. 10 contiguous slices with 2.5  mm cubic voxel resolution, 3 wave components, 8 time steps, and 2 averages were acquired at 7 mechanical excitation frequencies from 30 to 60  Hz. The total imaging time was approximately 15  min. For postprocessing, multifrequency dual elasto-visco (MDEV) inversion was used to calculate high-resolution mechanical parameter maps of the abdomen including the liver and spleen. RESULTS Two parameters maps were generated from each image slice to capture the magnitude and the phase angle of the complex shear modulus. Both parameters depicted the mechanical structures of the abdomen with unprecedented high spatial resolution. Spatially averaged group mean values of the liver and spleen are 1.27 ± 0.17 kPa and 2.01 ± 0.69 kPa, indicating a significantly higher asymptomatic stiffness of the spleen compared to the liver. CONCLUSION Patient-activated respiratory-gated 3D-MMRE combined with MDEV inversion provides highly resolved mechanical maps of the liver and spleen that are superior to previous elastograms measured by abdominal MRE.

Horizontal shear wave scattering from a nonwelded interface observed by magnetic resonance elastography

A method based on magnetic resonance elastography is presented that allows measuring the weldedness of interfaces between soft tissue layers. The technique exploits the dependence of shear wave scattering at elastic interfaces on the frequency of vibration. Experiments were performed on gel phantoms including differently welded interfaces. Plane wave excitation parallel to the planar interface with corresponding motion sensitization enabled the observation of only shear-horizontal (SH) wave scattering. Spatio-temporal filtering was applied to calculate scattering coefficients from the amplitudes of the incident, transmitted and reflected SH-waves in the vicinity of the interface. The results illustrate that acoustic wave scattering in soft tissues is largely dependent on the connectivity of interfaces, which is potentially interesting for imaging tissue mechanics in medicine and biology.