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PURPOSE: Magnetic resonance elastography (MRE) maps the viscoelastic properties of soft tissues for diagnostic purposes. However, different MRE inversion methods yield different results, which hinder comparison of values, standardization, and establishment of quantitative MRE markers. Here, we introduce an expandable, open-access, webserver-based platform that offers multiple inversion techniques for multifrequency, 3D MRE data. METHODS: The platform comprises a data repository and standard MRE inversion methods including local frequency estimation (LFE), direct-inversion based multifrequency dual elasto-visco (MDEV) inversion, and wavenumber-based (k-) MDEV. The use of the platform is demonstrated in phantom data and in vivo multifrequency MRE data of the kidneys and brains of healthy volunteers. RESULTS: Detailed maps of stiffness were generated by all inversion methods showing similar detail of anatomy. Specifically, the inner renal cortex had higher shear wave speed (SWS) than renal medulla and outer cortex without lateral differences. k-MDEV yielded higher SWS values than MDEV or LFE (full kidney/brain k-MDEV: 2.71 ± 0.19/1.45 ± 0.14 m/s, MDEV: 2.14 ± 0.16/0.99 ± 0.11 m/s, LFE: 2.12 ± 0.15/0.89 ± 0.06 m/s). CONCLUSION: The freely accessible platform supports the comparison of MRE results obtained with different inversion methods, filter thresholds, or excitation frequencies, promoting reproducibility in MRE across community-developed methods.

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PURPOSE: To investigate the significance of collagen in predicting the aggressiveness of rectal tumors in patients, examined in vivo based on tomoelastography quantified stiffness and ex vivo by histologically measured collagen volume fraction (CVF). EXPERIMENTAL DESIGN: 170 patients with suspected rectal cancer were prospectively enrolled and underwent preoperative magnetic resonance imaging (MRI) and rectal tomoelastography, a technique based on multifrequency magnetic resonance elastography. Histopathologic analysis identified eighty patients with rectal cancer who were divided into subgroups by tumor-node (TN) stage, prognostic stage, and risk level. Rectal tumor stiffness was correlated with histopathologic CVF. Area-under-the-curve (AUC) and contingency analysis were used to evaluate the performance of rectal stiffness in distinguishing tumor stages which was compared to standard clinical MRI. RESULTS: In vivo tomoelastography revealed that rectal tumor stiffened significantly with increased TN stage (p<0.05). Tumors with poorly differentiated status, perineural and lymphovascular invasion also displayed higher stiffness than well-to-moderately differentiated, noninvasive tumors (all p<0.05). Similar to in vivo stiffness, CVF indicated an abnormally high collagen content in tumors with perineural invasion and poor differentiation status. CVF was also positively correlated with stiffness (p<0.05). Most importantly, both stiffness (AUROC: 0.82) and CVF (AUROC: 0.89) demonstrated very good diagnostic accuracy in detecting rectal tumors that have high risk for progressing to an aggressive state with poorer prognosis. CONCLUSION: In human rectal carcinomas, overexpression of collagen is correlated with increased tissue stiffness and high risk for tumor advancing more aggressively. In vivo tomoelastography quantifies rectal tumor stiffness which improves the diagnostic performance of standard MRI in the assessment of lymph nodes metastasis. Therefore, in vivo stiffness mapping by tomoelastography can predict rectal tumor aggressiveness and add diagnostic value to MRI.

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In tomoelastography, to achieve a final wave speed map by combining reconstructions obtained from all spatial directions and excitation frequencies, the use of weights is inevitable. Here, a new weighting scheme, which maximizes the signal-to-noise ratio (SNR) of the final wave speed map, has been proposed. To maximize the SNR of the final wave speed map, the use of squares of estimated SNR values of reconstructed individual maps has been proposed. Therefore, derivations of the SNR of the reconstructed wave speed maps have become necessary. Considering the noise on the complex MRI signal, the SNR of the reconstructed wave speed map was formulated by an analytical approach assuming a high SNR, and the results were verified using Monte Carlo simulations (MCSs). It has been assumed that the noise remains approximately Gaussian when the image SNR is high enough, despite the nonlinear operations in tomoelastography inversion. Hence, the SNR threshold was determined by comparing the SNR computed by MCSs and analytical approximations. The weighting scheme was evaluated for accuracy, spatial resolution and SNR performances on simulated phantoms. MR elastography (MRE) experiments on two different phantoms were conducted. Wave speed maps were generated for simulated 3D human abdomen MRE data and experimental human abdomen MRE data. The simulation results demonstrated that the SNR-weighted inversion improved the SNR performance of the wave speed map by a factor of two compared to the performance of the original (i.e., amplitude-weighted) reconstruction. In the case of a low SNR, no bias occurred in the wave speed map when SNR weighting was used, whereas 10% bias occurred when the original weighting (i.e., amplitude weighting) was used. Thus, while not altering the accuracy or spatial resolution of the wave speed map with the proposed weighting method, the SNR of the wave speed map has been significantly improved.

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PURPOSE: Magnetic resonance elastography (MRE) measures stiffness of soft tissues by analyzing their spatial harmonic response to externally induced shear vibrations. Many MRE methods use inversion-based reconstruction approaches, which invoke first- or second-order derivatives by finite difference operators (first- and second-FDOs) and thus give rise to a biased frequency dispersion of stiffness estimates. METHODS: We here demonstrate analytically, numerically, and experimentally that FDO-based stiffness estimates are affected by (1) noise-related underestimation of values in the range of high spatial wave support, that is, at lower vibration frequencies, and (2) overestimation of values due to wave discretization at low spatial support, that is, at higher vibration frequencies. RESULTS: Our results further demonstrate that second-FDOs are more susceptible to noise than first-FDOs and that FDO dispersion depends both on signal-to-noise ratio (SNR) and on a lumped parameter A, which is defined as wavelength over pixel size and over a number of pixels per stencil of the FDO. Analytical FDO dispersion functions are derived for optimizing A parameters at a given SNR. As a simple rule of thumb, we show that FDO artifacts are minimized when A/2 is in the range of the square root of 2SNR for the first-FDO or cubic root of 5SNR for the second-FDO. CONCLUSIONS: Taken together, the results of our study provide an analytical solution to a long-standing, well-recognized, yet unsolved problem in MRE postprocessing and might thus contribute to the ongoing quest for minimizing inversion artifacts in MRE.

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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.

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PURPOSE: To introduce in vivo multifrequency single-shot magnetic resonance elastography for full-FOV stiffness mapping of the mouse brain and to compare in vivo stiffness of neural tissues with different white-to-gray matter ratios. METHODS: Viscous phantoms and 10 C57BL-6 mice were investigated by 7T small-animal MRI using a single-shot spin-echo planar imaging magnetic resonance elastography sequence with motion-encoding gradients positioned before the refocusing pulse. Wave images were acquired over 10 minutes for 6 mechanical vibration frequencies between 900 and 1400 Hz. Stiffness maps of shear wave speed (SWS) were computed using tomoelastography data processing and compared with algebraic Helmholtz inversion (AHI) for signal-to-noise ratio (SNR) analysis. Different brain regions were analyzed including cerebral cortex, corpus callosum, hippocampus, and diencephalon. RESULTS: In phantoms, algebraic Helmholtz inversion-based SWS was systematically biased by noise and discretization, whereas tomoelastography-derived SWS was consistent over the full SNR range analyzed. Mean in vivo SWS of the whole brain was 3.76 ± 0.33 m/s with significant regional variation (hippocampus = 4.91 ± 0.49 m/s, diencephalon = 4.78 ± 0.78 m/s, cerebral cortex = 3.53 ± 0.29 m/s, and corpus callosum = 2.89 ± 0.17 m/s). CONCLUSION: Tomoelastography retrieves mouse brain stiffness within shorter scan times and with greater detail resolution than classical algebraic Helmholtz inversion-based magnetic resonance elastography. The range of SWS values obtained here indicates that mouse white matter is softer than gray matter at the frequencies investigated.

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PURPOSE: To demonstrate the feasibility of in vivo multifrequency magnetic resonance elastography (MRE) of the prostate using externally placed drivers. METHODS: Three pressurized-air drivers were used to excite shear waves within the prostate at vibration frequencies of 60, 70, and 80 Hz. Full 3D wave fields were acquired by multislice spin-echo echo-planar imaging in conjunction with tomoelastography wave speed recovery for generating full field-of-view stiffness maps. Twelve healthy volunteers were repeatedly scanned to analyze test-retest reproducibility. Five patients with suspected prostate cancer were investigated to demonstrate the clinical feasibility of the method. RESULTS: In healthy volunteers, the shear wave speed of the entire prostate was 2.24 ± 0.20 m/s with a repeatability coefficient of 0.14 m/s and 88% intraclass correlation coefficient. No significant difference between the peripheral zone (2.27 ± 0.20 m/s) and the central gland (2.22 ± 0.23 m/s) was observed. In patients, wave-speed maps displayed stiff regions consistent with the localization of suspicious masses detected by other imaging markers. CONCLUSIONS: The proposed method provides reproducible quantitative maps of tissue stiffness throughout the pelvic region and can easily be integrated into clinical imaging protocols. Clinical stiffness maps display many details of potential interest for cancer diagnosis. Magn Reson Med 79:1325-1333, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

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OBJECTIVES: Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). METHODS: 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. RESULTS: In NMOSD patients, a significant reduction of |G*| was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). CONCLUSIONS: MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. KEY POINTS: • Magnetic resonance elastography reveals diffuse cerebral tissue changes in patients with NMOSD. • Premature tissue softening in NMOSD patients indicates tissue degeneration. • Hypothesis of a widespread cerebral neurodegeneration in form of diffuse tissue alteration.

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PURPOSE: To analyze the relevance of the viscosity measurement as a liver diagnostic marker. MATERIALS AND METHODS: To determine the level of fibrosis, a Fibroscan test was performed on 40 subjects (10 healthy volunteers and 30 patients). Subsequently, multifrequency magnetic resonance elastography (MMRE) tests were made with a pneumatic driver at 60, 70, and 80 Hz. Phase images were analyzed with two different postprocessing methods, without (Method 1) and with (Method 2) the inversion algorithm (IA), using rheological models (Voigt, springpot) in order to characterize the viscoelastic properties (viscosity: η and elasticity: µ). RESULTS: MRE cartography of the viscous tendency (G″MRE_M2 ) measured within the region of interest (ROI) of the liver increased as a function of the level of fibrosis. Similar results were also obtained for the viscosity (ηmodels_M1 ) calculated with a postprocessing without IA. However, the viscosity (ηmodels_M2 ) remained constant with the stage of fibrosis when the postprocessing was composed of an IA. The experimental (µMRE_M1 and G'MRE_M2 ) and rheological (µmodels_M2 and µmodels_M1 ) elasticities always increased with the level of fibrosis regardless of the postprocessing method. CONCLUSION: The variation of the liver viscosity parameter as a function of postprocessing revealed that this parameter should be further investigated to demonstrate its relevance in clinical practice.

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