Tissue characterization using magnetic resonance elastography: preliminary results

The well-documented effectiveness of palpation as a diagnostic technique for detecting cancer and other diseases has provided motivation for developing imaging techniques for noninvasively evaluating the mechanical properties of tissue. A recently described approach for elasticity imaging, using propagating acoustic shear waves and phase-contrast MRI, has been called magnetic resonance elastography (MRE). The purpose of this work was to conduct preliminary studies to define methods for using MRE as a tool for addressing the paucity of quantitative tissue mechanical property data in the literature. Fresh animal liver and kidney tissue specimens were evaluated with MRE at multiple shear wave frequencies. The influence of specimen temperature and orientation on measurements of stiffness was studied in skeletal muscle. The results demonstrated that all of the materials tested (liver, kidney, muscle and tissue-simulating gel) exhibit systematic dependence of shear stiffness on shear rate. These data are consistent with a viscoelastic model of tissue mechanical properties, allowing calculation of two independent tissue properties from multiple-frequency MRE data: shear modulus and shear viscosity. The shear stiffness of tissue can be substantially affected by specimen temperature. The results also demonstrated evidence of shear anisotropy in skeletal muscle but not liver tissue. The measured shear stiffness in skeletal muscle was found to depend on both the direction of propagation and polarization of the shear waves.     

磁共振弹性成像的初步实验研究

目的：研究磁共振弹性成像（MRE）技术。方法：研制外部激发装置，设计成像脉冲序列，制作模拟人体软组织的体模。激发装置由序列控制，于体模表面产生低频率剪切波。脉冲序列采用梯度回波序列，在x、y或z轴上施加运动敏感梯度（MSG）。剪切波导致的介质内的周期性移位可使接收信号产生周期性相位位移，从测得的相位位移就能计算出每个体素的移位值，直接显示介质内剪切波的传播。通过调整相位偏置，获得一个完整周期内剪切波的动态传播图像。相位图经局部频率估算法（LFE）处理后计算出量化的弹性模景图。实验采用浓度为1．0％和1．5％不同弹性的琼脂凝胶体模，激发频率分别采用150Hz、200Hz、250Hz和300Hz。结果：MRE的相位图显示了剪切波在体模内的传播，剪切波的波长随激发频率和体模弹性变化。波长与激发频率呈反比，与体模弹性呈正比。剪切波的波长在不同激发频率和不同浓度体模之间呈严格的比例关系。计算出的弹性模量图清楚显示了两种浓度介质的弹性对比。结论：MRE的相位图可显示剪切波在介质内的传播，弹性图可量化和显示介质的弹性模量。     

Vibration safety limits for magnetic resonance elastography

Magnetic resonance elastography (MRE) has been demonstrated to have potential as a clinical tool for assessing the stiffness of tissue in vivo. An essential step in MRE is the generation of acoustic mechanical waves within a tissue via a coupled mechanical driver. Motivated by an increasing volume of human imaging trials using MRE, the objectives of this study were to audit the vibration amplitude of exposure for our IRB-approved human MRE studies, to compare these values to a conservative regulatory standard for vibrational exposure and to evaluate the applicability and implications of this standard for MRE. MRE displacement data were examined from 29 MRE exams, including the liver, brain, kidney, breast and skeletal muscle. Vibrational acceleration limits from a European Union directive limiting occupational exposure to whole-body and extremity vibrations (EU 2002/44/EC) were adjusted for time and frequency of exposure, converted to maximum displacement values and compared to the measured in vivo displacements. The results indicate that the vibrational amplitudes used in MRE studies are below the EU whole-body vibration limit, and the EU guidelines represent a useful standard that could be readily accepted by Institutional Review Boards to define standards for vibrational exposures for MRE studies in humans.     

Three-dimensional analysis of shear wave propagation observed by in vivo magnetic resonance elastography of the brain

Dynamic magnetic resonance elastography (MRE) is a non-invasive method for the quantitative determination of the mechanical properties of soft tissues in vivo. In MRE, shear waves are generated in the tissue and visualized using phase-sensitive MR imaging methods. The resulting two-dimensional (2-D) wave images can reveal in-plane elastic properties when possible geometrical biases of the wave patterns are taken into account. In this study, 3-D MRE experiments of in vivo human brain are analyzed to gain knowledge about the direction of wave propagation and to deduce in-plane elastic properties. The direction of wave propagation was determined using a new algorithm which identifies minimal wave velocities along rays from the surface into the brain. It was possible to quantify biases of the elastic parameters due to projections onto coronal, sagittal and transversal image planes in 2-D MRE. It was found that the in-plane shear modulus is increasingly overestimated when the image slice is displaced from narrow slabs of 2-5cm through the center of the brain. The mean shear modulus of the brain was deduced from 4-D wave data with about 3.5kPa. Using the proposed slice positions in 2-D MRE, this shear modulus can be reproduced with an acceptable error within a fraction of the full 3-D examination time.     

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo‐echo planar imaging (SE‐EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE‐EPI MRE sequence. A paired t‐test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland–Altman's analysis were performed to determine the reproducibility and repeatability of the SE‐EPI MRE‐derived shear stiffness measurements. The SE‐EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE‐EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.     

Calculation of shear stiffness in noise dominated magnetic resonance elastography data based on principal frequency estimation

Magnetic resonance elastography (MRE) is a non-invasive phase-contrast-based method for quantifying the shear stiffness of biological tissues. Synchronous application of a shear wave source and motion encoding gradient waveforms within the MRE pulse sequence enable visualization of the propagating shear wave throughout the medium under investigation. Encoded shear wave-induced displacements are then processed to calculate the local shear stiffness of each voxel. An important consideration in local shear stiffness estimates is that the algorithms employed typically calculate shear stiffness using relatively high signal-to-noise ratio (SNR) MRE images and have difficulties at an extremely low SNR. A new method of estimating shear stiffness based on the principal spatial frequency of the shear wave displacement map is presented. Finite element simulations were performed to assess the relative insensitivity of this approach to decreases in SNR. Additionally, ex vivo experiments were conducted on normal rat lungs to assess the robustness of this approach in low SNR biological tissue. Simulation and experimental results indicate that calculation of shear stiffness by the principal frequency method is less sensitive to extremely low SNR than previously reported MRE inversion methods but at the expense of loss of spatial information within the region of interest from which the principal frequency estimate is derived.     

A new approach to elastography using mutual information and finite elements

Historically, increased mechanical stiffness during tissue palpation exams has been associated with assessing organ health as well as with detecting the growth of a potentially life-threatening cell mass. As such, techniques to image elasticity parameters (i.e., elastography) have recently become of great interest to scientists. In this work, a new method of elastography will be introduced within the context of mammographic imaging. The elastography method proposed represents a non-rigid iterative image registration algorithm that varies material properties within a finite element model to improve registration. More specifically, regional measures of image similarity are used within an objective function minimization framework to reconstruct elasticity images of tissue stiffness. Numerical simulations illustrate: (1) the encoding of stiffness information within the context of a regional image similarity criterion, (2) the methodology for an iterative elastographic imaging framework and (3) elasticity reconstruction simulations. The real strength in this approach is that images from any modality (e.g., magnetic resonance, computed tomography, ultrasound. etc) that have sufficient anatomically-based intensity heterogeneity and remain consistent from a pre- to a post-deformed state could be used in this paradigm.     

Frequency-dependent viscoelastic parameters of mouse brain tissue estimated by MR elastography

Viscoelastic properties of mouse brain tissue were estimated non-invasively, in vivo, using magnetic resonance elastography (MRE) at 4.7 T to measure the dispersive properties of induced shear waves. Key features of this study include (i) the development and application of a novel MR-compatible actuation system which transmits vibratory motion into the brain through an incisor bar, and (ii) the investigation of the mechanical properties of brain tissue over a 1200 Hz bandwidth from 600-1800 Hz. Displacement fields due to propagating shear waves were measured during continuous, harmonic excitation of the skull. This protocol enabled characterization of the true steady-state patterns of shear wave propagation. Analysis of displacement fields obtained at different frequencies indicates that the viscoelastic properties of mouse brain tissue depend strongly on frequency. The average storage modulus (G') increased from approximately 1.6 to 8 kPa over this range; average loss modulus (G″) increased from approximately 1 to 3 kPa. Both moduli were well approximated by a power-law relationship over this frequency range. MRE may be a valuable addition to studies of disease in murine models, and to pre-clinical evaluations of therapies. Quantitative measurements of the viscoelastic parameters of brain tissue at high frequencies are also valuable for modeling and simulation of traumatic brain injury.     

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.     

An octahedral shear strain-based measure of SNR for 3D MR elastography

A signal-to-noise ratio (SNR) measure based on the octahedral shear strain (the maximum shear strain in any plane for a 3D state of strain) is presented for magnetic resonance elastography (MRE), where motion-based SNR measures are commonly used. The shear strain, γ, is directly related to the shear modulus, μ, through the definition of shear stress, τ = μγ. Therefore, noise in the strain is the important factor in determining the quality of motion data, rather than the noise in the motion. Motion and strain SNR measures were found to be correlated for MRE of gelatin phantoms and the human breast. Analysis of the stiffness distributions of phantoms reconstructed from the measured motion data revealed a threshold for both strain and motion SNR where MRE stiffness estimates match independent mechanical testing. MRE of the feline brain showed significantly less correlation between the two SNR measures. The strain SNR measure had a threshold above which the reconstructed stiffness values were consistent between cases, whereas the motion SNR measure did not provide a useful threshold, primarily due to rigid body motion effects.     

Overhauser‐enhanced magnetic resonance elastography

Magnetic resonance elastography (MRE) is a powerful technique to assess the mechanical properties of living tissue. However, it suffers from reduced sensitivity in regions with short T₂ and T₂* such as in tissue with high concentrations of paramagnetic iron, or in regions surrounding implanted devices. In this work, we exploit the longer T₂* attainable at ultra‐low magnetic fields in combination with Overhauser dynamic nuclear polarization (DNP) to enable rapid MRE at 0.0065 T. A 3D balanced steady‐state free precession based MRE sequence with undersampling and fractional encoding was implemented on a 0.0065 T MRI scanner. A custom‐built RF coil for DNP and a programmable vibration system for elastography were developed. Displacement fields and stiffness maps were reconstructed from data recorded in a polyvinyl alcohol gel phantom loaded with stable nitroxide radicals. A DNP enhancement of 25 was achieved during the MRE sequence, allowing the acquisition of 3D Overhauser‐enhanced MRE (OMRE) images with (1.5 × 2.7 × 9) mm³ resolution over eight temporal steps and 11 slices in 6 minutes. In conclusion, OMRE at ultra‐low magnetic field can be used to detect mechanical waves over short acquisition times. This new modality shows promise to broaden the scope of conventional MRE applications, and may extend the utility of low‐cost, portable MRI systems to detect elasticity changes in patients with implanted devices or iron overload. Copyright © 2016 John Wiley & Sons, Ltd.     

Magnetic resonance elastography of the lumbar back muscles: A preliminary study

Back pain is associated with increased lumbar paraspinal muscle (LPM) stiffness identified by manual palpation and strain elastography. Recently, magnetic resonance elastography (MRE) has allowed the stiffness of muscle to be characterized noninvasively in vivo, providing quantitative 3D stiffness maps (elastograms). The aim of this study was to characterize the stiffness (shear modulus, SM) of the LPM (multifidus and erector spinae) using MRE. MRE of the lumbar region was performed on seven adults in supine position. MRE was acquired in three muscular states: relaxed with outstretched legs, stretched with passive pelvis flexion, and contracted with outstretched legs and tightened trunk muscles. The mean SM was measured within a region of interest manually defined in the multifidus, erector spinae, and the entire paraspinal compartment. The intermuscular difference and the effects of stretching and contraction were assessed by ANOVA and t‐tests. At rest, the mean SM of the paraspinal compartment was 1.6 ± 0.2 kPa. It increased significantly with stretching to 1.65 ± 0.3 kPa, and with contraction to 2.0 ± 0.7 kPa. Irrespective of muscular state, the erector spinae was significantly stiffer than the multifidus. The multifidus underwent proportionally higher stiffness changes from rest to contraction and stretching. MRE can be used to measure the stiffness of the LPM in different muscular states. We hypothesize that, irrespective of posture, the erector spinae behaves as semi‐rigid beam, and ensures permanent stiffness of the spine. The multifidus behaves as an adaptable muscle that provides segmental flexibility to the spine and tunes the spine stiffness. Clin. Anat. 31:514–520, 2018. © 2018 Wiley Periodicals, Inc.     

In vivo brain viscoelastic properties measured by magnetic resonance elastography

Magnetic resonance elastography (MRE) is a non-invasive imaging technique used to visualise and quantify mechanical properties of tissue, providing information beyond what can be currently achieved with standard MR sequences and could, for instance, provide new insight into pathological processes in the brain. This study uses the MRE technique at 3 T to extract the complex shear modulus for in vivo brain tissue utilizing a full three-dimensional approach to reconstruction, removing contributions of the dilatational wave by application of the curl operator. A calibrated phantom is used to benchmark the MRE measurements, and in vivo results are presented for healthy volunteers. The results provide data for in vivo brain storage modulus (G'), finding grey matter (3.1 kPa) to be significantly stiffer than white matter (2.7 kPa). The first in vivo loss modulus (G') measurements show no significant difference between grey matter (2.5 kPa) and white matter (2.5 kPa).     

Effects of frequency- and direction-dependent elastic materials on linearly elastic MRE image reconstructions

The mechanical model commonly used in magnetic resonance elastography (MRE) is linear elasticity. However, soft tissue may exhibit frequency- and direction-dependent (FDD) shear moduli in response to an induced excitation causing a purely linear elastic model to provide an inaccurate image reconstruction of its mechanical properties. The goal of this study was to characterize the effects of reconstructing FDD data using a linear elastic inversion (LEI) algorithm. Linear and FDD phantoms were manufactured and LEI images were obtained from time-harmonic MRE acquisitions with variations in frequency and driving signal amplitude. LEI responses to artificially imposed uniform phase shifts in the displacement data from both purely linear elastic and FDD phantoms were also evaluated. Of the variety of FDD phantoms considered, LEI appeared to tolerate viscoelastic data-model mismatch better than deviations caused by poroelastic and anisotropic mechanical properties in terms of visual image contrast. However, the estimated shear modulus values were substantially incorrect relative to independent mechanical measurements even in the successful viscoelastic cases and the variations in mean values with changes in experimental conditions associated with uniform phase shifts, driving signal frequency and amplitude were unpredictable. Overall, use of LEI to reconstruct data acquired in phantoms with FDD material properties provided biased results under the best conditions and significant artifacts in the worst cases. These findings suggest that the success with which LEI is applied to MRE data in tissue will depend on the underlying mechanical characteristics of the tissues and/or organs systems of clinical interest.     

Magnetic resonance elastography of skeletal muscle deep tissue injury

The current state‐of‐the‐art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury development is therefore highly desired. In this paper we quantified the spatial–temporal changes in mechanical properties upon damage development and recovery in a rat model of deep tissue injury. Deep tissue injury was induced in nine rats by two hours of sustained deformation of the tibialis anterior muscle. Magnetic resonance elastography (MRE), T₂‐weighted, and T₂‐mapping measurements were performed before, directly after indentation, and at several timepoints during a 14‐day follow‐up. The results revealed a local hotspot of elevated shear modulus (from 3.30 ± 0.14 kPa before to 4.22 ± 0.90 kPa after) near the center of deformation at Day 0, whereas the T₂ was elevated in a larger area. During recovery there was a clear difference in the time course of the shear modulus and T₂. Whereas T₂ showed a gradual normalization towards baseline, the shear modulus dropped below baseline from Day 3 up to Day 10 (from 3.29 ± 0.07 kPa before to 2.68 ± 0.23 kPa at Day 10, P < 0.001), followed by a normalization at Day 14. In conclusion, we found an initial increase in shear modulus directly after two hours of damage‐inducing deformation, which was followed by decreased shear modulus from Day 3 up to Day 10, and subsequent normalization. The lower shear modulus originates from the moderate to severe degeneration of the muscle. MRE stiffness values were affected in a smaller area as compared with T₂. Since T₂ elevation is related to edema, distributing along the muscle fibers proximally and distally from the injury, we suggest that MRE is more specific than T₂ for localization of the actual damaged area.     

Fibroscan : un outil non invasif de mesure de la dureté du foie par élastométrie

Fibroscan^® is a new medical device that measures liver stiffness noninvasively. The method is based on one-dimensional transient elastography. Ultrasound signals (3,5 MHz) are used to follow the propagation of a low-frequency shear elastic wave (50 Hz) that propagates at a velocity that depends on liver stiffness. Measurement is performed on the right lobe of the liver using a probe that is placed on the skin surface. Result is obtained at the end of examination that takes about 5 minutes. Pilot and multicentre studies have shown that liver stiffness is strongly correlated to fibrosis stage obtained from liver biopsy on patients with chronic hepatitis C. Fibroscan^® could be used to improve the evaluation of patients with liver chronic diseases by reducing the number of liver biopsies and by allowing the following of treatments.     

Visualization and quantification of breast cancer biomechanical properties with magnetic resonance elastography

A quasistatic magnetic resonance elastography (MRE) method for the evaluation of breast cancer is proposed. Using a phase contrast, stimulated echo MRI approach, strain imaging in phantoms and volunteers is presented. First-order assessment of tissue biomechanical properties based on inverse strain mapping is outlined and demonstrated. The accuracy of inverse strain imaging is studied through simulations in a two-dimensional model and in an anthropomorphic, three-dimensional finite-element model of the breast. To improve the accuracy of modulus assessment by elastography, inverse methods are discussed as an extension to strain imaging, and simulations quantify MRE in terms of displacement signal/noise required for robust inversion. A direct inversion strategy providing information on tissue modulus and pressure distribution is described along with a novel iterative method utilizing a priori knowledge of tissue geometry. It is shown that through the judicious choice of information from previous contrast-enhanced MRI breast images, MRE data acquisition requirements can be significantly reduced while maintaining robust modulus reconstruction in the presence of strain noise. An experimental apparatus for clinical breast MRE and preliminary images of a normal volunteer are presented.     

Magnetic resonance microscopy for monitoring osteogenesis in tissue-engineered construct in vitro

Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue-engineered constructs. Measurements of the developing tissue's MR relaxation times (T(1) and T(2)), apparent diffusion coefficient (ADC) and elastic shear modulus were conducted over a 4-week growth period using an 11.74 T Bruker spectrometer with an imaging probe adapted for MR elastography (MRE). Both the relaxation times and the ADC show a statistically significant decrease after only one week of tissue development while the tissue stiffness increases progressively during the first two weeks of in vitro growth. The measured MR parameters are correlated with histologically monitored osteogenic tissue development. This study shows that MRM can provide quantitative data with which to characterize the growth and development of tissue-engineered bone.     

Magnetic resonance elastography using 3D gradient echo measurements of steady-state motion

Magnetic resonance elastography (MRE) is an important new method used to measure the elasticity or stiffness of tissues in vivo. While there are many possible applications of MRE, breast cancer detection and classification is currently the most common. Several groups have been developing methods based on MR and ultrasound (US). MR or US is used to estimate the displacements produced by either quasi-static compression or dynamic vibration of the tissue. An important advantage of MRE is the possibility of measuring displacements accurately in all three directions. The central problem in most versions of MRE is recovering elasticity information from the measured displacements. In previous work, we have presented simulation results in two and three dimensions that were promising. In this article, accurate reconstructions of elasticity images from 3D, steady-state experimental data are reported. These results are significant because they demonstrate that the process is truly three-dimensional even for relatively simple geometries and phantoms. Further, they show that the integration of displacement data acquisition and elastic property reconstruction has been successfully achieved in the experimental setting. This process involves acquiring volumetric MR phase images with prescribed phase offsets between the induced mechanical motion and the motion-encoding gradients, converting this information into a corresponding 3D displacement field and estimating the concomitant 3D elastic property distribution through model-based image reconstruction. Fully 3D displacement fields and resulting elasticity images are presented for single and multiple inclusion gel phantoms.