Wide-range dynamic magnetic resonance elastography

Tissue mechanical parameters have been shown to be highly sensitive to disease by elastography. Magnetic resonance elastography (MRE) in the human body relies on the low-dynamic range of tissue mechanics <100 Hz. In contrast, MRE suited for investigations of mice or small tissue samples requires vibration frequencies 10–20 times higher than those used in human MRE. The dispersion of the complex shear modulus (G^?) prevents direct comparison of elastography data at different frequency bands and, consequently, frequency-independent viscoelastic models that fit to G^* over a wide dynamic range have to be employed. This study presents data of G^* of samples of agarose gel, liver, brain, and muscle measured by high-resolution MRE in a 7T-animal scanner at 200–800 Hz vibration frequency. Material constants μ and α according to the springpot model and related to shear elasticity and slope of the G^*-dispersion were determined. Both μ and α of calf brain and bovine liver were found to be similar, while a sample of fibrotic human liver (METAVIR score of 3) displayed about fifteen times higher shear elasticity, similar to μ of bovine muscle measured in muscle fiber direction. α was the highest in fibrotic liver, followed by normal brain and liver, while muscle had the lowest α-values of all biological samples investigated in this study. As expected, the least G^*-dispersion was seen in soft gel. The proposed technique of wide-range dynamic MRE can provide baseline data for both human MRE and high-dynamic MRE for better understanding tissue mechanics of different tissue structures.     

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies.     

Using static preload with magnetic resonance elastography to estimate large strain viscoelastic properties of bovine liver

Traditional magnetic resonance elastography (MRE) applies small amplitude vibration to tissues. Thus currently MRE measures only the small deformation behaviour of tissues. MRE has the potential to estimate the strain-varying shear modulus of soft tissues, if applied at different static strains, which may allow prediction of the large-strain behaviour of tissues. This study uses MRE of bovine liver specimens under various levels of static compressive pre-strain up to 30%. Storage and loss moduli measured using MRE increased non-linearly with static compressive pre-strain, and exponential models fit well to these data to describe this relationship (R²>0.93). Based on these models, a 10% linear compression of liver would result in a 47% overestimate of the ‘true’ storage modulus of the uncompressed tissue. The results of this study have implications for MRE transducer design and interpretation of results from in vivo MRE studies.     

Anisotropic mechanical properties of magnetically aligned fibrin gels measured by magnetic resonance elastography

The anisotropic mechanical properties of magnetically aligned fibrin gels were measured by magnetic resonance elastography (MRE) and by a standard mechanical test: unconfined compression. Soft anisotropic biomaterials are notoriously difficult to characterize, especially in vivo. MRE is well-suited for efficient, non-invasive, and non-destructive assessment of shear modulus. Direction-dependent differences in shear modulus were found to be statistically significant for gels polymerized at magnetic fields of 11.7 and 4.7 T compared to control gels. Mechanical anisotropy was greater in the gels polymerized at the higher magnetic field. These observations were consistent with results from unconfined compression tests. Analysis of confocal microscopy images of gels showed measurable alignment of fibrils in gels polymerized at 11.7 T. This study provides direct, quantitative measurements of the anisotropy in mechanical properties that accompanies fibril alignment in fibrin gels.     

High-resolution mechanical imaging of the kidney

The objective of this study was to test the feasibility and reproducibility of in vivo high-resolution mechanical imaging of the asymptomatic human kidney. Hereby nine volunteers were examined at three different physiological states of urinary bladder filling (a normal state, urinary urgency, and immediately after urinary relief). Mechanical imaging was performed of the in vivo kidney using three-dimensional multifrequency magnetic resonance elastography combined with multifrequency dual elastovisco inversion. Other than in classical elastography, where the storage and loss shear moduli are evaluated, we analyzed the magnitude |G^?| and the phase angle φ of the complex shear modulus reconstructed by simultaneous inversion of full wave field data corresponding to 7 harmonic drive frequencies from 30 to 60 Hz and a resolution of 2.5 mm cubic voxel size.     

A finite element model for analyzing shear wave propagation observed in magnetic resonance elastography

Magnetic resonance elastography (MRE) is a novel non-invasive approach to determine material stiffness by using a conventional magnetic resonance imaging (MRI) system incorporated with an oscillating motion-sensitizing gradient to detect nodal displacements produced by a shear excitation wave. The effects of material properties, excitation frequency, boundary conditions, and applied tension on shear wavelength measurement must be examined before MRE can become a useful diagnostic tool. We propose finite element (FE) modeling as a robust method to systematically study the effects of these parameters. An axisymmetric FE model was generated with ABAQUS to simulate agarose gel phantoms. The effects of material stiffness, density, and excitation frequency on propagating shear wavelength were examined individually. The effect of the boundary conditions on shear wavelength was also demonstrated. Results of shear wavelength from MRE measurement were compared with the results of FE model, which showed good agreement between the methods.     

Wideband MRE and static mechanical indentation of human liver specimen: Sensitivity of viscoelastic constants to the alteration of tissue structure in hepatic fibrosis

Despite the success of elastography in grading hepatic fibrosis by stiffness related noninvasive markers the relationship between viscoelastic constants in the liver and tissue structure remains unclear. We therefore studied the mechanical properties of 16 human liver specimens with different degrees of fibrosis, inflammation and steatosis by wideband magnetic resonance elastography (MRE) and static indentation experiments providing the specimens? static Young?s modulus (E), dynamic storage modulus (G′) and dynamic loss modulus (G″). A frequency-independent shear modulus μ and a powerlaw exponent α were obtained by fitting G′ and G″ using the two-parameter sprinpot model. The mechanical parameters were compared to the specimens? histology derived parameters such as degree of Fibrosis (F), inflammation score and fat score, amount of hydroxyproline (HYP) used for quantification of collagen, blood markers and presurgery in vivo function tests.     

多核19F磁共振成像研究进展

~(19)氟(~(19)F)的磁共振成像(MRI)研究可追溯到35年以上。在这段时间里,~1H磁共振成像的蓬勃发展使磁共振成为影像医学的支柱,但~(19)F磁共振成像研究的进展却较为缓慢。然而最近几年,~(19)F磁共振成像的研究受到了广泛的关注。在某种程度上,这是由于MR成像中软件与硬件的发展,更因为分子影像学的概念的提出与发展。本文将对~(19)F多核磁共振成像的应用,特别是使用全氟化碳纳米成像探针的19F多核磁共振成像进行综述。     

Magnetic resonance assessment of parenchymal elasticity in normal and edematous, ventilator-injured lung

Magnetic resonance elastography (MRE) is a MR imaging method capable of spatially resolving the intrinsic mechanical properties of normal lung parenchyma. We tested the hypothesis that the mechanical properties of edematous lung exhibit local properties similar to those of a fluid-filled lung at transpulmonary pressures (P(tp)) up to 25 cm H(2)O. Pulmonary edema was induced in anesthetized female adult Sprague-Dawley rats by mechanical ventilation to a pressure of 40 cm H(2)O for ～30 min. Prior to imaging the wet weight of each ex vivo lung set was measured. MRE, high-resolution T(1)-weighted spin echo and T(2)* gradient echo data were acquired at each P(tp) for both normal and injured ex vivo lungs. At P(tp)s of 6 cm H(2)O and greater, the shear stiffness of normal lungs was greater than injured lungs (P ≤ 0.0003). For P(tp)s up to 12 cm H(2)O, shear stiffness was equal to 1.00, 1.07, 1.16, and 1.26 kPa for the injured and 1.31, 1.89, 2.41, and 2.93 kPa for normal lungs at 3, 6, 9, and 12 cm H(2)O, respectively. For injured lungs MRE magnitude signal and shear stiffness within regions of differing degrees of alveolar flooding were calculated as a function of P(tp). Differences in shear stiffness were statistically significant between groups (P < 0.001) with regions of lower magnitude signal being stiffer than those of higher signal. These data demonstrate that when the alveolar space filling material is fluid, MRE-derived parenchymal shear stiffness of the lung decreases, and the lung becomes inherently softer compared with normal lung.     

Measurement of the dynamic shear modulus of mouse brain tissue in vivo by magnetic resonance elastography

In this study, the magnetic resonance (MR) elastography technique was used to estimate the dynamic shear modulus of mouse brain tissue in vivo. The technique allows visualization and measurement of mechanical shear waves excited by lateral vibration of the skull. Quantitative measurements of displacement in three dimensions during vibration at 1200 Hz were obtained by applying oscillatory magnetic field gradients at the same frequency during a MR imaging sequence. Contrast in the resulting phase images of the mouse brain is proportional to displacement. To obtain estimates of shear modulus, measured displacement fields were fitted to the shear wave equation. Validation of the procedure was performed on gel characterized by independent rheometry tests and on data from finite element simulations. Brain tissue is, in reality, viscoelastic and nonlinear. The current estimates of dynamic shear modulus are strictly relevant only to small oscillations at a specific frequency, but these estimates may be obtained at high frequencies (and thus high deformation rates), noninvasively throughout the brain. These data complement measurements of nonlinear viscoelastic properties obtained by others at slower rates, either ex vivo or invasively.     

Sensitivity of multifrequency magnetic resonance elastography and diffusion-weighted imaging to cellular and stromal integrity of liver tissue

Microscopic structural alterations of liver tissue induced by freeze-thaw cycles give rise to palpable property changes. However, the underlying damage to tissue architecture is difficult to quantify histologically, and published data on macroscopic changes in biophysical properties are sparse.To better understand the influence of hepatic cells and stroma on global biophysical parameters, we studied rat liver specimens freshly taken (within 30 min after death) and treated by freeze-thaw cycles overnight at either −20 °C or –80 °C using diffusion-weighted imaging (DWI) and multifrequency magnetic resonance elastography (MRE) performed at 0.5 T in a tabletop MRE scanner. Tissue structure was analyzed histologically and rheologic data were analyzed using fractional order derivatives conceptualized by a called spring-pot component that interpolates between pure elastic and viscous responses.Overnight freezing and thawing induced membrane disruptions and cell detachment in the space of Disse, resulting in a markedly lower shear modulus μ and apparent diffusion coefficient (ADC) (μ[−20 °C] = 1.23 ± 0.73 kPa, μ[−80 °C] = 0.66 ± 0.75 kPa; ADC[–20 °C] = 0.649 ± 0.028 μm²/s, ADC[−80 °C] = 0.626 ± 0.025 μm²/s) compared to normal tissue (μ = 9.92 ± 3.30 kPa, ADC = 0.770 ± 0.023 μm²/s, all p < 0.001). Furthermore, we analyzed the springpot-powerlaw coefficient and observed a reduction in −20 °C specimens (0.22 ± 0.14) compared to native tissue (0.40 ± 0.10, p = 0.033) and −80 °C specimens (0.54 ± 0.22, p = 0.002), that correlated with histological observations of sinusoidal dilation and collagen distortion within the space of Disse. Overall, the results suggest that shear modulus and water diffusion in liver tissue markedly decrease due to cell membrane degradation and cell detachment while viscosity-related properties appear to be more sensitive to distorted stromal and microvascular architecture.     

Quantifying the Elastic Property of Nine Thigh Muscles Using Magnetic Resonance Elastography

BackgroundPathologies of the muscles can manifest different physiological and functional changes. To adapt treatment, it is necessary to characterize the elastic property (shear modulus) of single muscles. Previous studies have used magnetic resonance elastography (MRE), a technique based on MRI technology, to analyze the mechanical behavior of healthy and pathological muscles. The purpose of this study was to develop protocols using MRE to determine the shear modulus of nine thigh muscles at rest.MethodsTwenty-nine healthy volunteers (mean age = 26 ± 3.41 years) with no muscle abnormalities underwent MRE tests (1.5 T MRI). Five MRE protocols were developed to quantify the shear moduli of the nine following thigh muscles at rest: rectus femoris (RF), vastus medialis (VM), vastus intermedius (VI), vastus lateralis (VL), sartorius (Sr), gracilis (Gr), semimembranosus (SM), semitendinosus (ST), and biceps (BC). In addition, the shear modulus of the subcutaneous adipose tissue was analyzed.ResultsThe gracilis, sartorius, and semitendinosus muscles revealed a significantly higher shear modulus (μ_{_Gr} = 6.15 ± 0.45 kPa, μ_{_ Sr} = 5.15 ± 0.19 kPa, and μ_{_ ST} = 5.32 ± 0.10 kPa, respectively) compared to other tissues (from μ_{_ RF} = 3.91 ± 0.16 kPa to μ_{_VI} = 4.23 ± 0.25 kPa). Subcutaneous adipose tissue had the lowest value (μ_{_adipose tissue} = 3.04 ± 0.12 kPa) of all the tissues tested.ConclusionThe different elasticities measured between the tissues may be due to variations in the muscles'' physiological and architectural compositions. Thus, the present protocol could be applied to injured muscles to identify their behavior of elastic property. Previous studies on muscle pathology found that quantification of the shear modulus could be used as a clinical protocol to identify pathological muscles and to follow-up effects of treatments and therapies. These data could also be used for modelling purposes.     

Viscoelastic properties of the tongue and soft palate using MR elastography

Biomechanical properties of the human tongue are needed for finite element models of the upper airway and may be important to elucidate the pathophysiology of obstructive sleep apneoa. Tongue viscoelastic properties have not been characterized previously. Magnetic resonance elastography (MRE) is an emerging imaging technique that can measure the viscoelastic properties of soft tissues in-vivo. In this study, MRE was used to measure the viscoelastic properties of the tongue and soft palate in 7 healthy volunteers during quiet breathing. Results show that the storage shear modulus of the tongue and soft palate is 2.67±0.29 and 2.53±0.31 kPa (mean ± SD), respectively. This is the first study to investigate the mechanical properties of the tongue using MRE, and it provides necessary data for future studies of patient groups with altered upper airway function.     

生物组织弹性成像方法及其新技术进展

弹性是一种描述物质物理意义的重要参数,在描述物质在热力学和动力学的变化过程中有着重要的意义。在医学上,弹性的变化往往和病变联系在一起。然而,绝大多数生物组织在他们的力学特性上所表现出的复杂性并不是弹性模量一项参数就可以完全表述的,在对于他们的粘弹性表征和流变学行为的描述中,粘滞性往往和弹性一样的重要。现在被广泛用来对生物组织机械特性表征的成像技术是弹性成像,其基本原理是给组织施加一个激励,组织会产生一个响应,而该响应的分布结合技术的处理方法,可以反映出其弹性模量等力学属性的差异。本文介绍了生物组织常见的弹性成像方法:超声弹性成像,磁共振弹性成像以及光学相干弹性成像;详细阐述了新发展起来的技术-光声弹性成像和光声粘弹成像,并讨论分析其应用前景。     

Mechanical Stimulation of Chondrocyte-agarose Hydrogels

Articular cartilage suffers from a limited repair capacity when damaged by mechanical insult or degraded by disease, such as osteoarthritis. To remedy this deficiency, several medical interventions have been developed. One such method is to resurface the damaged area with tissue-engineered cartilage; however, the engineered tissue typically lacks the biochemical properties and durability of native cartilage, questioning its long-term survivability. This limits the application of cartilage tissue engineering to the repair of small focal defects, relying on the surrounding tissue to protect the implanted material. To improve the properties of the developed tissue, mechanical stimulation is a popular method utilized to enhance the synthesis of cartilaginous extracellular matrix as well as the resultant mechanical properties of the engineered tissue. Mechanical stimulation applies forces to the tissue constructs analogous to those experienced in vivo. This is based on the premise that the mechanical environment, in part, regulates the development and maintenance of native tissue^1,2. The most commonly applied form of mechanical stimulation in cartilage tissue engineering is dynamic compression at physiologic strains of approximately 5-20% at a frequency of 1 Hz^1,3. Several studies have investigated the effects of dynamic compression and have shown it to have a positive effect on chondrocyte metabolism and biosynthesis, ultimately affecting the functional properties of the developed tissue^4-8. In this paper, we illustrate the method to mechanically stimulate chondrocyte-agarose hydrogel constructs under dynamic compression and analyze changes in biosynthesis through biochemical and radioisotope assays. This method can also be readily modified to assess any potentially induced changes in cellular response as a result of mechanical stimuli.     

Direct noninvasive measurement and numerical modeling of depth-dependent strains in layered agarose constructs

Biomechanical factors play an important role in the growth, regulation, and maintenance of engineered biomaterials and tissues. While physical factors (e.g. applied mechanical strain) can accelerate regeneration, and knowledge of tissue properties often guide the design of custom materials with tailored functionality, the distribution of mechanical quantities (e.g. strain) throughout native and repair tissues is largely unknown. Here, we directly quantify distributions of strain using noninvasive magnetic resonance imaging (MRI) throughout layered agarose constructs, a model system for articular cartilage regeneration. Bulk mechanical testing, giving both instantaneous and equilibrium moduli, was incapable of differentiating between the layered constructs with defined amounts of 2% and 4% agarose. In contrast, MRI revealed complex distributions of strain, with strain transfer to softer (2%) agarose regions, resulting in amplified magnitudes. Comparative studies using finite element simulations and mixture (biphasic) theory confirmed strain distributions in the layered agarose. The results indicate that strain transfer to soft regions is possible in vivo as the biomaterial and tissue changes during regeneration and maturity. It is also possible to modulate locally the strain field that is applied to construct-embedded cells (e.g. chondrocytes) using stratified agarose constructs.     

Magnetic resonance elastography in nonlinear viscoelastic materials under load

Characterisation of soft tissue mechanical properties is a topic of increasing interest in translational and clinical research. Magnetic resonance elastography (MRE) has been used in this context to assess the mechanical properties of tissues in vivo noninvasively. Typically, these analyses rely on linear viscoelastic wave equations to assess material properties from measured wave dynamics. However, deformations that occur in some tissues (e.g. liver during respiration, heart during the cardiac cycle, or external compression during a breast exam) can yield loading bias, complicating the interpretation of tissue stiffness from MRE measurements. In this paper, it is shown how combined knowledge of a material’s rheology and loading state can be used to eliminate loading bias and enable interpretation of intrinsic (unloaded) stiffness properties. Equations are derived utilising perturbation theory and Cauchy’s equations of motion to demonstrate the impact of loading state on periodic steady-state wave behaviour in nonlinear viscoelastic materials. These equations demonstrate how loading bias yields apparent material stiffening, softening and anisotropy. MRE sensitivity to deformation is demonstrated in an experimental phantom, showing a loading bias of up to twofold. From an unbiased stiffness of \(4910.4 \pm 635.8\) Pa in unloaded state, the biased stiffness increases to 9767.5 \(\pm \,\)1949.9 Pa under a load of \(\approx \) 34% uniaxial compression. Integrating knowledge of phantom loading and rheology into a novel MRE reconstruction, it is shown that it is possible to characterise intrinsic material characteristics, eliminating the loading bias from MRE data. The framework introduced and demonstrated in phantoms illustrates a pathway that can be translated and applied to MRE in complex deforming tissues. This would contribute to a better assessment of material properties in soft tissues employing elastography.

     

Identification of the testing parameters in high frequency dynamic shear measurement on agarose gels

Dynamic mechanical analysis (DMA) on agarose gels can be used to validate magnetic resonance elastography (MRE) measurements as well as to provide better understanding for the biological responses of cells to the dynamic loadings in cell culture studies. Various parameters potentially affecting the repeatability and accuracy of the DMA shear modulus measurements were investigated systematically in the present study, including sample thickness, shear strain, testing frequency, and compressive clamping strain. The study showed that the thickness of the agarose gel sample must be sufficiently small (1 mm) to prevent the erroneous fluctuation in the measured modulus. The appropriate levels of shear strain (< or = 0.5%) and compressive clamping strain (5-10%) must be applied to overcome the slippage at the gel-clamp interface without causing significant boundary and stress non-uniformity or micro-cracks in the agarose gel sample.     

Assessment of in vivo and post-mortem mechanical behavior of brain tissue using magnetic resonance elastography

The knowledge of in vivo brain tissue mechanical properties is essential in several biomedical engineering fields, such as injury biomechanics and neurosurgery simulation. Almost all existing available data have been obtained in vitro by invasive experimental protocols. However, the difference between in vivo and post-mortem mechanical properties remains poorly known, essentially due to the lack of a common method that could measure them both in vivo and ex vivo. In this study, we report the use of magnetic resonance elastography (MRE) for the non-invasive assessment of in vivo brain tissue viscoelastic properties and for the investigation of their evolution after the death. Experiments were performed on seven adult male rats. Shear storage and loss moduli were measured in vivo, just after death and at post-mortem time of approximately 24h. A significant increase in shear storage modulus G(') of approximately 100% was found to occur just after death (p=0.002), whereas no significant difference was found between in vivoG(') and G(') at 24h post-mortem time. No significant difference was found between shear loss modulus G(')in vivo and just after death, whereas a decrease of about 50% was found to occur after 24h (p=0.02). These results illustrate the ability of MRE to investigate some of the critical soft tissue biomechanics-related issues, as it can be used as a non-invasive tool for measuring soft tissue viscoelastic properties.