Developments in dynamic MR elastography for in vitro biomechanical assessment of hyaline cartilage under high-frequency cyclical shear

The design, construction, and evaluation of a customized dynamic magnetic resonance elastography (MRE) technique for biomechanical assessment of hyaline cartilage in vitro are described. For quantification of the dynamic shear properties of hyaline cartilage by dynamic MRE, mechanical excitation and motion sensitization were performed at frequencies in the kilohertz range. A custom electromechanical actuator and a z-axis gradient coil were used to generate and image shear waves throughout cartilage at 1000-10,000 Hz. A radiofrequency (RF) coil was also constructed for high-resolution imaging. The technique was validated at 4000 and 6000 Hz by quantifying differences in shear stiffness between soft ( approximately 200 kPa) and stiff ( approximately 300 kPa) layers of 5-mm-thick bilayered phantoms. The technique was then used to quantify the dynamic shear properties of bovine and shark hyaline cartilage samples at frequencies up to 9000 Hz. The results demonstrate that one can obtain high-resolution shear stiffness measurements of hyaline cartilage and small, stiff, multilayered phantoms at high frequencies by generating robust mechanical excitations and using large magnetic field gradients. Dynamic MRE can potentially be used to directly quantify the dynamic shear properties of hyaline and articular cartilage, as well as other cartilaginous materials and engineered constructs.     

健康志愿者头部MR弹性成像研究

目的 应用MR弹性成像(MRE)技术评估健康志愿者脑组织的剪切模量,并了解脑组织剪切模量与年龄间是否存在相关性.方法 选取105名健康志愿者,其中男42名、女63名,行头部MRE检查.通过局部频率估算法(LFE)分别测量志愿者脑灰质与脑白质的剪切模量.采用独立样本t检验评估脑灰质与脑白质剪切模量间是否存在差异,以及脑实质剪切模量是否存在性别差异;应用Spearman相关分析评估剪切模量与年龄是否存在相关性,并将志愿者分为≤40岁组(76名)和>40岁组(29名),分别进行脑实质剪切模量与年龄间的相关性分析.结果 105名健康志愿者脑白质的剪切模量[(23.1±5.7)kPa]高于脑灰质[(11.3±2.6)kPa],两者间差异具有统计学意义(t=19.34,P<0.01).男性志愿者脑白质与脑灰质的剪切模量分别为(23.4±5.8)、(11.4±2.8)kPa,女性志愿者分别为(22.8±5.6)、(11.1±2.5)kPa.男、女志愿者脑组织间剪切模量值差异无统计学意义(t值分别为-0.534、-0.606,P值均>0.05).年龄相关性分析显示,灰质的剪切模量与年龄呈正相关(r=0.315,P<0.01),白质的剪切模量与年龄无相关性(r=0.183,P>0.05);≤40岁组志愿者灰、白质剪切模量与年龄呈正相关(r值分别为0.251、0.235,P值均<0.05),而>40岁组志愿者脑灰、白质剪切模量均与年龄无相关性(r值分别为0.181、-0.001,P值均>0.05).结论 健康志愿者脑白质的剪切模量明显高于脑灰质;脑实质剪切模量男女之间无差别;脑灰质剪切模量随年龄增加而增加.     

TREMR: Table‐resonance elastography with MR

Magnetic resonance elastography (MRE) is a noninvasive method of measuring tissue compliance. Current MRE methods rely on custom‐built hardware to elicit vibrations that are tracked by MR imaging. Knowledge of the wave propagation can be used to calculate the local shear stiffness of the tissue. We sought to determine whether the vibrations of the patient table that result from low‐frequency switching of the imaging gradients could be used as an alternative mechanical driving mechanism for MRE. We designed a pulse sequence that includes a gradient lobe specifically for the excitation of mechanical resonance, allowing control of the time between the onset of the vibrations and the velocity‐encoding of the readout. Data collected from a gelatin phantom with stiff cylindrical gelatin inserts demonstrated that wave propagation can be imaged with this method. Postprocessing to estimate the local spatial frequency of the waves also allows estimation of the local shear stiffness, where the stiff inserts are clearly identifiable. Data collected on the brain of a normal healthy volunteer showed clear rotational waves propagating from the skull inwards, also allowing generation of shear stiffness maps. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Needle shear wave driver for magnetic resonance elastography.

Magnetic resonance elastography (MRE) is capable of quantitatively depicting the mechanical properties of tissues in vivo. In contrast to mechanical excitation at the surface of the tissue, the method proposed in this study describes shear waves produced by an inserted needle. The results demonstrate that MRE performed with the needle driver provides shear stiffness estimates that correlate well with those obtained using mechanical testing. Comparisons between MRE acquisitions obtained with surface and needle drivers yielded similar results in general. However, the well-defined wave propagation pattern provided by the needle driver in a target region can reduce section orientation-related error in wavelength estimation that occurs with surface drivers in 2D MRE acquisitions. Preliminary testing of the device was performed on animals. This study demonstrates that the needle driver is an effective option that offers advantages over surface drivers for obtaining accurate stiffness estimates in targeted regions that are accessible by the needle.     

Evaluation of renal parenchymal disease in a rat model with magnetic resonance elastography.

Alterations in the mechanical properties or "hardness" of tissues allow physicians to detect disease by palpation. Recently, attempts have been made to quantitate and image these tissue properties with the use of magnetic resonance elastography (MRE). This technique has been validated in ex vivo specimens, including kidney, breast, and prostate. In this study, in vivo MRE imaging of rat renal cortex is demonstrated and validated with a disease model that will facilitate further studies. Normal rats and rats with nephrocalcinosis induced with either 2 or 4 weeks of ethylene glycol exposure were studied with MRE. Histology in the diseased rats documented the presence of nephrocalcinosis. MRE measurements and images of shear stiffness were highly reproducible in individual rats. The shear stiffness of the renal cortex in normal rats was 3.87 kPa (95% CI 2.84-4.90 kPa). The shear stiffness increased to 5.02 kPa (95% CI 3.34-6.70 kPa) after 2 weeks of exposure, and to 6.49 kPa (95% CI 4.84-8.14 kPa) after 4 weeks of exposure (P = 0.0302, alpha < 0.05). MRE is capable of detecting alterations in the tissue mechanical properties of kidneys in vivo. It is a promising noninvasive technique that might have pathologic and prognostic significance.     

In vivo magnetic resonance elastography of human brain at 7 T and 1.5 T

Purpose:

To investigate the feasibility of quantitative in vivo ultrahigh field magnetic resonance elastography (MRE) of the human brain in a broad range of low‐frequency mechanical vibrations.

Materials and Methods:

Mechanical vibrations were coupled into the brain of a healthy volunteer using a coil‐driven actuator that either oscillated harmonically at single frequencies between 25 and 62.5 Hz or performed a superimposed motion consisting of multiple harmonics. Using a motion sensitive single‐shot spin‐echo echo planar imaging sequence shear wave displacements in the brain were measured at 1.5 and 7 T in whole‐body MR scanners. Spatially averaged complex shear moduli were calculated applying Helmholtz inversion.

Results:

Viscoelastic properties of brain tissue could be reliably determined in vivo at 1.5 and 7 T using both single‐frequency and multifrequency wave excitation. The deduced dispersion of the complex modulus was consistent within different experimental settings of this study for the measured frequency range and agreed well with literature data.

Conclusion:

MRE of the human brain is feasible at 7 T. Superposition of multiple harmonics yields consistent results as compared to standard single‐frequency based MRE. As such, MRE is a system‐independent modality for measuring the complex shear modulus of in vivo human brain in a wide dynamic range. J. Magn. Reson. Imaging 2010;32:577–583. © 2010 Wiley‐Liss, Inc.     

Comparison of quantitative shear wave MR-elastography with mechanical compression tests.

The mechanical properties of in vivo soft tissue are generally determined by palpation, ultrasound measurements (US), and magnetic resonance elastography (MRE). While it has been shown that US and MRE are capable of quantitatively measuring soft tissue elasticity, there is still some uncertainty about the reliability of quantitative MRE measurements. For this reason it was decided to determine in vitro how MRE measurements correspond with other quantitative methods of measuring characteristic elasticity values. This article presents the results of experiments with tissue-like agar-agar gel phantoms in which the wavelength of strain waves was measured by shear wave MR elastography and the resultant shear modulus was compared with results from mechanical compression tests with small gel specimens. The shear moduli of nine homogeneous gels with various agar-agar concentrations were investigated. The elasticity range of the gels covered the elasticity range of typical soft tissues. The systematic comparison between shear wave MRE and compression tests showed good agreement between the two measurement techniques.     

Determination of thigh muscle stiffness using magnetic resonance elastography

PURPOSE: To measure the elastic properties of the vastus lateralis (VL), vastus medialis (VM), and sartorius (Sr) muscles using magnetic resonance elastography (MRE). MATERIALS AND METHODS: To obtain a normative database of the aforementioned muscles, oblique scan directions were prescribed passing through each muscle. Shear waves were induced into the muscles using pneumatic and mechanical drivers at 90 and 120 Hz, respectively. These drivers were attached to the distal end of the right thigh with the knee flexed at 30 degrees . The foot was placed in a footplate containing MR-compatible load cells to record the force during a contraction (10% and 20% of the maximum voluntary contraction). RESULTS: The shear moduli measured at rest in the VL (N = 12), VM (N = 14), and Sr (N = 13) were 3.73 +/- 0.85 kPa, 3.91 +/- 1.15 kPa, and 7.53 +/- 1.63 kPa, respectively. The stiffness of both vasti increased with the level of contraction, while the stiffness of the Sr remained the same. CONCLUSION: The MRE technique was able to approximate the stiffness of different thigh muscles. Furthermore, the wave length was sensitive to the morphology (unipennate or longitudinal) and fiber composition (type I or II) in each muscle.     

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 patient's 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.     

Quantitative shear wave magnetic resonance elastography: comparison to a dynamic shear material test.

Magnetic resonance elastography (MRE), a phase contrast MRI technique, images the propagation of applied mechanical waves in tissue, allowing shear stiffness to be quantified in vivo. This MRE technique has been validated with static mechanical compression tests. Dynamic mechanical analysis (DMA) may be a more appropriate comparison to MRE because it directly measures the shear modulus dynamically, while compression tests convert the measured elastic modulus to shear modulus with an assumed Poisson ratio. This study compared the shear stiffness estimated with various MRE inversion algorithms (i.e., manual calculation, local frequency estimate, phase gradient, direct inversion, and matched filter) to the dynamic mechanical test. The shear stiffness of five agarose gels with concentrations ranging from 1.5 to 3.5% were measured using MRE and DMA. The phase gradient inversion algorithm overestimated the shear modulus at higher concentrations (i.e., 3-3.5% agar), while the results from the other techniques correlated well with the dynamic mechanical test.     

Acoustic Radiation Force Impulse (ARFI) Imaging: a Review

Acoustic radiation force based elasticity imaging methods are under investigation by many groups. These methods differ from traditional ultrasonic elasticity imaging methods in that they do not require compression of the transducer, and are thus expected to be less operator dependent. Methods have been developed that utilize impulsive (i.e. < 1 ms), harmonic (pulsed), and steady state radiation force excitations. The work discussed herein utilizes impulsive methods, for which two imaging approaches have been pursued: 1) monitoring the tissue response within the radiation force region of excitation (ROE) and generating images of relative differences in tissue stiffness (Acoustic Radiation Force Impulse (ARFI) imaging); and 2) monitoring the speed of shear wave propagation away from the ROE to quantify tissue stiffness (Shear Wave Elasticity Imaging (SWEI)). For these methods, a single ultrasound transducer on a commercial ultrasound system can be used to both generate acoustic radiation force in tissue, and to monitor the tissue displacement response. The response of tissue to this transient excitation is complicated and depends upon tissue geometry, radiation force field geometry, and tissue mechanical and acoustic properties. Higher shear wave speeds and smaller displacements are associated with stiffer tissues, and slower shear wave speeds and larger displacements occur with more compliant tissues. ARFI images have spatial resolution comparable to that of B-mode, often with greater contrast, providing matched, adjunctive information. SWEI images provide quantitative information about the tissue stiffness, typically with lower spatial resolution. A review these methods and examples of clinical applications are presented herein.     

磁共振弹性成像技术在肿瘤中的应用及研究进展

肿瘤组织的硬度与肿瘤的发展、浸润、远处转移、放化疗抵抗以及手术方式的选择密切相关,因此准确评估肿瘤组织硬度对于肿瘤的诊断、手术方式的选择及预后评估具有重要意义。磁共振弹性成像是通过机械波定量测量组织弹性剪切力的动态成像方法。磁共振弹性成像作为一种非侵入性的技术可以定量分析在体组织的机械性能（硬度）。它是传统触诊机械化、定量化的一种手段,不仅客观且分辨率高,又不受诊断部位的限制,因此具有良好的研究和应用前景。笔者将综述目前磁共振弹性成像的原理以及其在乳腺、前列腺、脑、肝脏及胰腺等肿瘤中的应用和研究进展。     

Magnetic resonance elastography of the brain using multishot spiral readouts with self‐navigated motion correction

Magnetic resonance elastography (MRE) has been introduced in clinical practice as a possible surrogate for mechanical palpation, but its application to study the human brain in vivo has been limited by low spatial resolution and the complexity of the inverse problem associated with biomechanical property estimation. Here, we report significant improvements in brain MRE data acquisition by reporting images with high spatial resolution and signal‐to‐noise ratio as quantified by octahedral shear strain metrics. Specifically, we have developed a sequence for brain MRE based on multishot, variable‐density spiral imaging, and three‐dimensional displacement acquisition and implemented a correction scheme for any resulting phase errors. A Rayleigh damped model of brain tissue mechanics was adopted to represent the parenchyma and was integrated via a finite element‐based iterative inversion algorithm. A multiresolution phantom study demonstrates the need for obtaining high‐resolution MRE data when estimating focal mechanical properties. Measurements on three healthy volunteers demonstrate satisfactory resolution of gray and white matter, and mechanical heterogeneities correspond well with white matter histoarchitecture. Together, these advances enable MRE scans that result in high‐fidelity, spatially resolved estimates of in vivo brain tissue mechanical properties, improving upon lower resolution MRE brain studies that only report volume averaged stiffness values. Magn Reson Med 70:404–412, 2013. © 2012 Wiley Periodicals, Inc.     

MR elastography as a method for the assessment of myocardial stiffness: Comparison with an established pressure–volume model in a left ventricular model of the heart

Magnetic resonance elastography (MRE) measurements of shear stiffness (μ) in a spherical phantom experiencing both static and cyclic pressure variations were compared to those derived from an established pressure–volume (P‐V)‐based model. A spherical phantom was constructed using a silicone rubber composite of 10 cm inner diameter and 1.3 cm thickness. A gradient echo MRE sequence was used to determine μ within the phantom at static and cyclic pressures ranging from 55 to 90 mmHg. Average values of μ using MRE were obtained within a region of interest and were compared to the P‐V‐derived estimates. Under both static and cyclic pressure conditions, the P‐V‐ and MRE‐based estimates of μ ranged from 98.2 to 155.1 kPa and 96.2 to 150.8 kPa, respectively. Correlation coefficients (R²) of 0.98 and 0.97 between the P‐V and MRE‐based estimates of shear stiffness measurements were obtained. For both static and cyclic pressures, MRE‐based measures of μ agree with those derived from a P‐V model, suggesting that MRE can be used as a new, noninvasive method of assessing μ in sphere‐like fluid‐filled organs such as the heart. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

MR elastography for noninvasive assessment of hepatic fibrosis: experience from a tertiary center in Asia

Purpose:

To determine the sensitivity and specificity of MR elastography (MRE) in the staging of hepatic fibrosis (HF) using histopathology as the reference standard in an Asian population.

Materials and Methods:

MRE was performed on 55 patients with chronic liver diseases or biliary diseases and on 5 living related liver donors (48 men and 12 women; mean age, 55.7 years). MRE was performed with modified, phase‐contrast, gradient‐echo sequences, and the mean stiffness values were measured on the elastograms in kilopascals(kPa). Receiver operating characteristic curve analysis was performed to determine the cutoff value and accuracy of MRE for staging HF. Histopathologic staging of HF according to the METAVIR scoring system served as the reference.

Results:

Liver stiffness increased systematically along with the fibrosis stage. With a shear stiffness cutoff value of 3.05 kPa, the predicted sensitivity and specificity for differentiating significant liver fibrosis (≥ F2) from mild fibrosis (F1) were 89.7% and 87.1%, respectively. In addition, MRE was able to discriminate between patients with severe fibrosis (F3) and those with liver cirrhosis (sensitivity, 100%; specificity, 92.2%), with a shear stiffness cutoff value of 5.32 kPa.

Conclusion:

MRE could be a promising, noninvasive technique with excellent diagnostic accuracy for detecting significant HF and liver cirrhosis. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.     

Microscopic magnetic resonance elastography (microMRE).

Magnetic resonance elastography (MRE) was extended to the microscopic scale to image low-frequency acoustic shear waves (typically less than 1 kHz) in soft gels and soft biological tissues with high spatial resolution (34 micromx34 micromx500 microm). Microscopic MRE (microMRE) was applied to agarose gel phantoms, frog oocytes, and tissue-engineered adipogenic and osteogenic constructs. Analysis of the low-amplitude shear wave pattern in the samples allowed the material stiffness and viscous loss properties (complex shear stiffness) to be identified with high spatial resolution. microMRE experiments were conducted at 11.74 T in a 56-mm vertical bore magnet with a 10 mm diameterx75 mm length cylindrical space available for the elastography imaging system. The acoustic signals were generated at 550-585 Hz using a piezoelectric transducer and high capacitive loading amplifier. Shear wave motion was applied in synchrony with the MR pulse sequence. The field of view (FOV) ranged from 4 to 14 mm for a typical slice thickness of 0.5 mm. Increasing the agarose gel concentration resulted in an increase in shear elasticity and shear viscosity. Shear wave motion propagated through the frog oocyte nucleus, enabling the measurement of its shear stiffness, and in vitro shear wave images displayed contrast between adipogenic and osteogenic tissue-engineered constructs. Further development of microMRE should enable its use in characterizing stiffer materials (e.g., polymers, composites, articular cartilage) and assessing with high resolution the mechanical properties of developing tissues.     

Decreased brain stiffness in Alzheimer's disease determined by magnetic resonance elastography

Purpose:

To test patient acceptance and reproducibility of the 3D magnetic resonance elastography (MRE) brain exam using a soft vibration source, and to determine if MRE could noninvasively measure a change in the elastic properties of the brain parenchyma due to Alzheimer's disease (AD).

Materials and Methods:

MRE exams were performed using an accelerated spin‐echo echo planar imaging (EPI) pulse sequence and stiffness was calculated with a 3D direct inversion algorithm. Reproducibility of the technique was assessed in 10 male volunteers, who each underwent four MRE exams separated into two imaging sessions. The effect of AD on brain stiffness was assessed in 28 volunteers, 7 with probable AD, 14 age‐ and gender‐matched PIB‐negative (Pittsburgh Compound B, a PET amyloid imaging ligand) cognitively normal controls (CN?), and 7 age‐ and gender‐matched PIB‐positive cognitively normal controls (CN+).

Results:

The median stiffness of the 10 volunteers was 3.07 kPa with a range of 0.40 kPa. The median and maximum coefficients of variation for these volunteers were 1.71% and 3.07%. The median stiffness of the 14 CN? subjects was 2.37 kPa (0.44 kPa range) compared to 2.32 kPa (0.49 kPa range) within the CN+ group and 2.20 kPa (0.33 kPa range) within the AD group. A significant difference was found between the three groups (P = 0.0055, Kruskal–Wallis one‐way analysis of variance). Both the CN+ and CN? groups were significantly different from the AD group.

Conclusion:

3D MRE of the brain can be performed reproducibly and demonstrates significantly reduced brain tissue stiffness in patients with AD. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.

     

Harnessing brain waves: a review of brain magnetic resonance elastography for clinicians and scientists entering the field

Brain magnetic resonance elastography (MRE) is an imaging technique capable of accurately and non-invasively measuring the mechanical properties of the living human brain. Recent studies have shown that MRE has potential to provide clinically useful information in patients with intracranial tumors, demyelinating disease, neurodegenerative disease, elevated intracranial pressure, and altered functional states. The objectives of this review are: (1) to give a general overview of the types of measurements that have been obtained with brain MRE in patient populations, (2) to survey the tools currently being used to make these measurements possible, and (3) to highlight brain MRE-based quantitative biomarkers that have the highest potential of being adopted into clinical use within the next 5 to 10 years. The specifics of MRE methodology strategies are described, from wave generation to material parameter estimations. The potential clinical role of MRE for characterizing and planning surgical resection of intracranial tumors and assessing diffuse changes in brain stiffness resulting from diffuse neurological diseases and altered intracranial pressure are described. In addition, the emerging technique of functional MRE, the role of artificial intelligence in MRE, and promising applications of MRE in general neuroscience research are presented.     

Rapid magnetic resonance elastography of muscle using one-dimensional projection

PURPOSE: To demonstrate the feasibility of 1D MR elastography (MRE) to rapidly assess skeletal muscle stiffness in vivo. MATERIALS AND METHODS: Shear waves were induced in the vastus medialis muscle (VM) using a pneumatic driver at 90 Hz and 2D MRE data were collected. Spatially selective excitations were used to produce 1D projections of MRE data oriented along the direction of propagating waves in the muscle. Data were collected with the thigh muscles relaxed and contracted at 20% maximum voluntary contraction (MVC) and the knee flexed at 30 degrees . RESULTS: The muscle stiffness measured at rest and in contraction with 1D MRE was 3.69 +/- 0.80 kPa and 9.52 +/- 2.74 kPa, respectively, and 4.36 +/- 0.98 kPa and 9.22 +/- 1.29 kPa, respectively, with the 2D MRE technique. CONCLUSION: Muscle stiffness measured using 1D MRE was in agreement with 2D MRE while reducing the scan time by a factor of 4.