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.     

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).     

Preliminary assessment of one-dimensional MR elastography for use in monitoring focused ultrasound therapy

The purpose of this work is to assess a fast technique that measures tissue stiffness and temperature during focused ultrasound thermal therapy (FUS). A one-dimensional (1D) MR elastography (MRE) pulse sequence was evaluated for the purpose of obtaining rapid measurements of thermally induced changes in tissue stiffness and temperature for monitoring FUS treatments. The accuracy of the 1D measurement was studied by comparing tissue displacements measured by 1D MRE with those measured by the well-established 2D MRE pulse sequence. The reproducibility of the 1D MRE measurement was assessed, in gel phantoms and ex vivo porcine tissue, for varied FUS intensity levels (31.5-199.9 W cm(-2)) and over a range of displacements at the focus (0.1-1 microm). Temperature elevations in agarose gel phantoms were measured using 1D MRE and calibrated using fiberoptic-thermometer-based measurements. The 1D MRE displacement measurements are highly correlated with those obtained with the 2D technique (R(2) = 0.88-0.93), indicating that 1D MRE can successfully measure tissue displacement. Ten repeated trials at each FUS power level yielded a minimum detectable displacement change of 0.2 microm in phantoms and 0.4 microm in tissue (at 95% confidence level). The 1D MRE temperature measurements correlated well with temperature changes measured simultaneously with fiberoptic thermometers (R(2) = 0.97). The 1D MRE technique is capable of detecting tissue displacements as low as 0.4 microm, which is an order of magnitude smaller than 5 microm displacements expected during FUS therapy (Le et al 2005 AIP Conf. Proc.: Ther. Ultrasound 829 186-90). Additionally, 1D MRE was shown to provide adequate measurements of temperature elevations in tissue. These findings indicate that 1D MRE may be an effective tool for monitoring FUS treatments.     

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.     

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.     

The effects of acceleration on the mechanical impedance response of a primate model exposed to sinusoidal vibration

Criteria for developing active and passive isolation mechanisms for reducing the effects of whole-body vibration exposure rely on a thorough understanding of the stiffness, damping, and resonance behaviors of the human or human surrogate body. Three Rhesus monkeys were exposed to seated whole-body sinusoidal vibration between 3 and 20 Hz at 0.69 and 3.47 msec⁻² rms (0.1 and 0.5 g peak) accelerations. The mechanical impedance magnitude and phase were calculated as the ratio and phase relation between the transmitted force and input velocity, respectively, at the seat. The resultant profiles showed a significant decrease in the primary resonance frequency with increasing acceleration. At the lower acceleration level, a second lower impedance peak was observed at approximately 5 Hz. A three-mass, two degree-of-freedom model, which included upper torso and leg representation, was used to determine the mechanical parameters that best described the measured responses. The mean stiffness coefficients and the mean undamped natural frequencies associated with the upper torso and leg subsystems showed a significant decrease with increases in the acceleration level. The results of this study strongly suggested that nonlinear stiffness properties were responsible for the observed differences in the biodynamic response of the Rhesus monkey with acceleration level.     

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.     

Non-invasive quantitative reconstruction of tissue elasticity using an iterative forward approach

A novel iterative approach is presented to estimate Young's modulus in homogeneous soft tissues using vibration sonoelastography. A low-frequency (below 100 Hz) external vibration is applied and three or more consecutive frames of B-scan image data are recorded. The internal vibrational motion of the soft tissue structures is calculated from 2D displacements between pairs of consecutive frames, which are estimated using a mesh-based speckle tracking method. An iterative forward finite element approach has been developed to reconstruct Young's modulus from the measured vibrational motion. This is accomplished by subdividing the 2D image domain into sample blocks in which Young's modulus is assumed to be constant. Because the finite element equations are internally consistent, boundary values other than displacement are not required. The sensitivity of the results to Poisson's ratio and the damping coefficient (viscosity) is investigated. The approach is verified using simulated displacement data and using data from tissue-mimicking phantoms.     

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.     

MR elastography of prostate cancer: quantitative comparison with histopathology and repeatability of methods

The purpose of this work was to assess trans‐perineal prostate magnetic resonance elastography (MRE) for (1) repeatability in phantoms/volunteers and (2) diagnostic power as correlated with histopathology in prostate cancer patients. The three‐dimensional (3D) displacement field was obtained using a fractionally encoded gradient echo sequence using a custom‐made transducer. The repeatability of the method was assessed based on three repeat studies and by changing the driving frequency by 3% in studies on a phantom and six healthy volunteers. Subsequently, 11 patients were examined with MRE prior to radical prostatectomy. The areas under the receiver operating characteristic curves were calculated using a windowed voxel‐to‐voxel approach by comparing the 2D registered slides, masked with the Gleason score. For the repeatability study, the average intraclass correlation coefficient for elasticity images was 99% for repeat phantom studies, 98% for ±6 Hz phantom studies, 95% for volunteer repeat studies with 2 min acquisition time, 82% for ±2 Hz volunteer studies with 2 min acquisition time and 73% for repeat volunteer studies with 8 min acquisition time. For the patient study, the average elasticity was 8.2 ± 1.7 kPa in the prostate capsule, 7.5 ± 1.9 kPa in the peripheral zone (PZ), 9.7 ± 3.0 kPa in the central gland (CG) and 9.0 ± 3.4 kPa in the transition zone. In the patient study, cancerous tissue with Gleason score at least 3 + 3 was significantly (p < 0.05) different from normal tissue in 10 out of 11 cases with tumors in the PZ, and 6 out of 9 cases with tumors in the CG. However, the overall case‐averaged area under the curve was 0.72 in the PZ and 0.67 in the CG. Cancerous tissue was not always stiffer than normal tissue. The inversion algorithm was sensitive to (i) vibration amplitude and displacement nodes and (ii) misalignment of the 3D wave field due to subject movement. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Deleterious effects of whole‐body vibration on the spine: A review of in vivo,ex vivo,and in vitro models

Occupational exposure to whole‐body vibration is associated with the development of musculoskeletal, neurological, and other ailments. Low back pain and other spine disorders are prevalent among those exposed to whole‐body vibration in occupational and military settings. Although standards for limiting exposure to whole‐body vibration have been in place for decades, there is a lack of understanding of whole‐body vibration‐associated risks among safety and healthcare professionals. Consequently, disorders associated with whole‐body vibration exposure remain prevalent in the workforce and military. The relationship between whole‐body vibration and low back pain in humans has been established largely through cohort studies, for which vibration inputs that lead to symptoms are rarely, if ever, quantified. This gap in knowledge highlights the need for the development of relevant in vivo, ex vivo, and in vitro models to study such pathologies. The parameters of vibrational stimuli (eg, frequency and direction) play critical roles in such pathologies, but the specific cause‐and‐effect relationships between whole‐body vibration and spinal pathologies remain mostly unknown. This paper provides a summary of whole‐body vibration parameters; reviews in vivo, ex vivo, and in vitro models for spinal pathologies resulting from whole‐body vibration; and offers suggestions to address the gaps in translating injury biomechanics data to inform clinical practice.     

振动对急性缺氧小鼠肺损伤的影响

本文观察了频率为20Hz、振幅为0．67mm和作用时间为40min的振动预处理对急性缺氧小鼠肺损伤的影响。结果发现实验组的肺组织匀浆脂质过氧化物LghdPeroxde（LPO）、支气管肺泡灌洗液（BALF）中蛋白含量和白细胞数明显低于对照组（P＜0．05）。这表明在特定率数的振动作用下能明显减轻急性缺氧小鼠肺的损伤。     

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.     

A high pulse repetition frequency ultrasound system for the ex vivo measurement of mechanical properties of crystalline lenses with laser-induced microbubbles interrogated by acoustic radiation force

A high pulse repetition frequency ultrasound system for an ex vivo measurement of mechanical properties of an animal crystalline lens was developed and validated. We measured the bulk displacement of laser-induced microbubbles created at different positions within the lens using nanosecond laser pulses. An impulsive acoustic radiation force was applied to the microbubble, and spatio-temporal measurements of the microbubble displacement were assessed using a custom-made high pulse repetition frequency ultrasound system consisting of two 25 MHz focused ultrasound transducers. One of these transducers was used to emit a train of ultrasound pulses and another transducer was used to receive the ultrasound echoes reflected from the microbubble. The developed system was operating at 1 MHz pulse repetition frequency. Based on the measured motion of the microbubble, Young's moduli of surrounding tissue were reconstructed and the values were compared with those measured using the indentation test. Measured values of Young's moduli of four bovine lenses ranged from 2.6 ± 0.1 to 26 ± 1.4 kPa, and there was good agreement between the two methods. Therefore, our studies, utilizing the high pulse repetition frequency ultrasound system, suggest that the developed approach can be used to assess the mechanical properties of ex vivo crystalline lenses. Furthermore, the potential of the presented approach for in vivo measurements is discussed.     

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.     

Changes of cerebral vasoactive intestinal polypeptide-and somatostatin-like immunoreactivity induced by noise and whole-body vibration in the rat

To clarify the role of vasoactive intestinal polypeptide (VIP) and somatostatin, somatropin-release inhibiting factor, (SRIF) neurons in the response to organisms to noise or whole-body vibration stress, VIP and SRIF-like immunoreactivity were determined in various regions of the rat brain following exposure for 90 min to noise (broad band, 102 dB) or whole-body vibration (20 Hz, 4.0 g). Both noise and whole-body vibration significantly increased VIP-like immunoreactivity in the amygdala. A significant reduction of VIP like immunoreactivity in the hippocampus was induced only by whole-body vibration. On the other hand SRIF-like immunoreactivity was decreased significantly in the hypothalamus and increased significantly in the amygdala by noise and whole-body vibration, respectively. The present findings would seem to indicate that the amygdalofugal VIP neural system is involved in regulating hypothalamic and pituitary hormone secretions in non-specific reactions to stress. Responses of hippocampal VIP and the amygdalofugal SRIF to whole-body vibration stress are assumed to be activated as specific reactions to the stress.     

Viscoelastic properties of soft gels: comparison of magnetic resonance elastography and dynamic shear testing in the shear wave regime

Magnetic resonance elastography (MRE) is used to quantify the viscoelastic shear modulus, G*, of human and animal tissues. Previously, values of G* determined by MRE have been compared to values from mechanical tests performed at lower frequencies. In this study, a novel dynamic shear test (DST) was used to measure G* of a tissue-mimicking material at higher frequencies for direct comparison to MRE. A closed-form solution, including inertial effects, was used to extract G* values from DST data obtained between 20 and 200 Hz. MRE was performed using cylindrical 'phantoms' of the same material in an overlapping frequency range of 100-400 Hz. Axial vibrations of a central rod caused radially propagating shear waves in the phantom. Displacement fields were fit to a viscoelastic form of Navier's equation using a total least-squares approach to obtain local estimates of G*. DST estimates of the storage G' (Re[G*]) and loss modulus G″ (Im[G*]) for the tissue-mimicking material increased with frequency from 0.86 to 0.97 kPa (20-200 Hz, n = 16), while MRE estimates of G' increased from 1.06 to 1.15 kPa (100-400 Hz, n = 6). The loss factor (Im[G*]/Re[G*]) also increased with frequency for both test methods: 0.06-0.14 (20-200 Hz, DST) and 0.11-0.23 (100-400 Hz, MRE). Close agreement between MRE and DST results at overlapping frequencies indicates that G* can be locally estimated with MRE over a wide frequency range. Low signal-to-noise ratio, long shear wavelengths and boundary effects were found to increase residual fitting error, reinforcing the use of an error metric to assess confidence in local parameter estimates obtained by MRE.     

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.