实时剪切波弹性成像量化评估健康人正中神经弹性特征的信度

背景：实时剪切波弹性成像技术可无创测量组织弹性,目前较多地应用于甲状腺、乳腺等软组织疾病,而应用于周围神经及其病变的研究相对少见。目的：使用实时剪切波弹性成像技术量化评估健康人正中神经的重测信度及测试者间信度,探究同一测量位点正中神经长轴与短轴弹性模量的相关性。方法：随机招募20名健康受试者参与该试验,10名男性,10名女性。在信度试验中,测试者A和B分别使用实时剪切波弹性成像技术测量受试者利手侧、非利手侧正中神经长轴放松状态时的弹性模量;5 d后,测试者A以相同的测量方法对受试者正中神经弹性进行量化评估。此外,使用实时剪切波弹性成像技术在受试者腕横纹处测量正中神经长轴以及短轴的弹性模量完成相关试验。结果与结论：(1)在信度试验中,利手侧正中神经的测试者间信度表现为优秀：其组内相关系数为0.98,重测信度优秀(组内相关系数=0.96);非利手侧,测试者间信度和重测信度均表现为好(组内相关系数=0.78,0.86);(2)正中神经长轴与其短轴弹性模量之间无相关性(r=0.039,P=0.87);(3)提示剪切波弹性成像技术能准确量化评估出健康人利手侧以及非利手侧正中神经弹性模量特征,且可...     

基于正交频率脉冲编码激励的软组织粘弹性定量测量

高频剪切波对粘性参数的准确估计非常重要。为了提高高频剪切波的检测能力,并研究其对粘弹性参数估计的影响,本研究探讨了基于正交频率脉冲激励的超声振动计方法。通过构造具有特定频谱特性的正交频率波形,经稀疏采样之后激励组织振动,可以增强剪切波的高频分量。以新鲜猪肝为对象进行离体实验。选择二进制编码和两种正交频率编码脉冲激励组织振动,然后分别运用激光振动计和超声对不同编码激励方式产生的剪切波进行检测。激光振动计实验证明了该方法可以有效增强剪切波的高频分量,而从超声实验结果上看,与二进制编码激励方式的结果相比,当只用100～400 Hz剪切波速度拟合求解时,三码片与六码片的正交频率脉冲激励所估计得到的剪切弹性和剪切粘性的相对偏差分别为2.3%和4.1%,13.6%和11.5%;而当将所有频率剪切波速度用于拟合求解时,三码片与六码片的正交频率脉冲激励所估计得到的剪切弹性和剪切粘性的相对偏差分别为10.6%和3.5%,5.4%和11.8%。实验结果表明,正交频率编码激励方式可以降低激励峰值声强,并提高系统对高频剪切波的检测能力;另一方面,高频剪切波对粘弹性估计值具有影响,但其影响方式还不确定,需要进一步研究。     

基于Zener模型的生物组织剪切模量测量

目的克服基于Voigt模型的超声振动检测方法的不足,使用Zener模型更加准确地测量生物组织剪切模量,为组织定征提供有效的手段。方法利用基于力学模型本构关系的剪切波传播速度公式,在获得剪切波在多个频率上速度的前提下,通过数学方法估计出介质的剪切模量。实验对象为不同浓度的凝胶模型和不同程度热力学损伤的猪肝脏,通过超声辐射力振动产生剪切波,获取剪切波在不同实验介质中的传播速度。结果分别用Voigt模型和Zener模型对速度值进行拟合,结果均显示Zener模型描述的准确性更高,并且所估计出的剪切模量能够很好地区分不同浓度的凝胶模型或不同损伤程度的猪肝。结论本方法为无创测量生物组织剪切模量提供了潜在的手段,对医学上的组织定征和疾病诊断有着重要的意义。     

人血粘弹特性对正弦剪切流频率的依从关系

研究血液粘弹性对正弦剪切流频率的依从关系,有助手深入了解血液粘弹性的本质。作者采用LowShear—30流变测定仪研究正弦剪切频率很低情况下(0.0401—0.259Hz)血流粘弹性与频率的关系,其结果;当正弦剪切流频率增高时,人血液粘性分量η′、弹性分量η″和松弛时间λ均呈指数曲线样下降。剪切弹性模量G′则随频率增高而线性增大。本文建立经验方程以描述频率f与η′、η″、λ和G′之间的关系,并讨论了这四个粘弹性参数的物理、生理意义这将有助于这些参数在临床血液流变学上的应用。     

实时剪切波弹性成像技术对成年人肝脏杨氏模量正常值的研究

目的探讨应用实时剪切波弹性成像技术评价正常人肝脏杨氏模量值的临床应用价值。方法553例健康志愿者,其中男性213例,女性340例;年龄2l～80岁,平均年龄50．4岁。按照年龄分为3组：青年组（20．39岁）183例,中年组（40～59岁）250例．老年组（60～80岁）120例。应用法国声威公司AixPlorer超声诊断仪,所有研究对象均首先进行常规超声检查,然后再进行肝脏超声剪切波弹性成像检查,并行肝脏杨氏模量值定量分析,于深度4cm处测量感兴趣区域（ROI）（直径：lcm）内测量肝组织杨氏模量值。结果553例研究对象总的肝脏杨氏模量值为（6．10±1．31）kPa;青年组、中年组、老年组分别为（5．72±1．25）kPa、（6．21±1．63）kPa、（6．26±1．74）kPa,青年组低于中年组、老年组（P〈0．05）;中年组与老年组及不同性别间比较差异无统计学意义（P〉0．05）。结论应用实时剪切波弹性成像技术可定量检测正常人肝组织的杨氏模量值．杨氏模量值与年龄有关．但与性别无关。应用实时剪切波弹性成像技术评价肝脏杨氏模量时应考虑年龄因素。     

基于剪切波频散超声振动的黏弹性检测系统开发

目的 为实现离体组织黏弹性检测,建立一套超声黏弹性检测系统。方法 该系统基于剪切波频散超声振动方法,利用超声辐射力激励组织产生谐波运动,然后检测振动产生的剪切波传播特性,从而估算组织的黏弹性值。采用该系统进行标准仿体实验和大鼠肝脏实验,并完成对系统的初步评估。结果 标准仿体的检测结果与仿体标定的弹性系数值接近,大鼠肝脏的黏性系数和弹性系数值分别为(1.12±0.41) Pa?s、（0.81±0.40）kPa。结论 通过标准仿体实验和大鼠肝脏的实验,证明采用该系统进行离体动物实验的可行性,为实现人体肝纤维化检测作初步探索。     

腰背部肌筋膜疼痛综合征激痛点的剪切波弹性模量研究

目的 通过剪切波弹性成像(SWE)技术研究肌筋膜疼痛综合征激痛点的弹性特征,探索弹性超声技术在肌筋膜疼痛综合征临床诊断中的应用价值.方法 对8例女性健康志愿者的8个正常点和15例女性肌筋膜疼痛综合征患者腰背部30个激痛点行弹性超声检查,分别获得正常点、激痛点病灶区及邻近区定量分析取样框(Q-box)内弹性模量的均值(Mean)、最小值(Min)、最大值(Max)及标准差(SD);比较正常点、激痛点病灶区及临近区的弹性模量差异,探索激痛点弹性模量与患者年龄、所在部位的关系.结果 激痛点病灶区弹性模量的均值、最小值、最大值、标准差显著高于邻近区及正常点,其差异具有统计学意义(P＜0.05);而邻近区与正常点的弹性模量差异无统计学意义(P＞0.05),两个年龄组和3个不同部位激痛点的弹性模量差异亦无统计学意义(P＞0.05).结论 剪切波弹性模量值可用于激痛点病灶区与临近区及正常组织的鉴别,为激痛点的定位提供了新方法,也为肌筋膜疼痛综合征的触诊提供了新依据,具有较高的临床应用价值和研究前景.     

周期性机械拉伸对C2C12成肌细胞增殖的影响

目的：探讨不同的周期性拉伸应变条件对C2C12成肌细胞增殖的影响。方法：周期性拉伸的各种力学条件通过BioFlex加载系统实现，采用应用流式细胞术和BrdU法对拉伸应变下的细胞增殖动力学变化进行分析，反映成肌细胞增殖情况。结果：不同的周期性机械拉伸条件影响C2C12细胞的增殖，拉伸的频率对C2C12细胞增殖有较大的影响。在0．5Hz拉伸频率下，2．5％、5％和10％的细胞变形幅度都不能促进细胞的增殖，其中10％（0．5Hz）的拉伸幅度抑制C2C12成肌细胞的增殖；而在0．125Hz拉伸频率下，10％的细胞变形幅度明显地促进C2C12成肌细胞的增殖。结论：较低的拉伸频率有利于成肌细胞的增殖，高频率的拉伸抑制成肌细胞的增殖。     

基于子波变换阿尔茨海默病脑电信号多尺度定量特征的研究

目的：研究阿尔茨海默病（AlzheimerDisease,AD）脑电信号的多尺度定量特征和相位平均波形。方法：采集32例重度AD患者,30例轻度AD患者和30例正常对照的清醒安静闭目状态下的脑电信号,进行Gauss连续子波变换,提取脑电信号的时频分布特征和多尺度功率谱分布特征;应用条件采样和相位平均的方法提取脑电信号分尺度相位平均波形。结果：AD脑电信号的时频结构特征表现为尺度单一,节律性活动紊乱,而正常对照脑电信号尺度结构丰富,在0．1Hz、1Hz和10Hz频带上形成稳定的节律性活动。AD患者脑电信号的多尺度功率谱分布特征表现为在1Hz附近出现窄而高的功率峰,而正常对照老年人脑电信号表现为在0．1Hz、1Hz和10Hz附近出现三个宽而低的功率峰。多尺度相位平均波形的结果显示,不同导联脑电信号第9尺度（频率中心10Hz）的相位平均波形的波长在重度AD组、轻度AD组和正常对照组三组之间比较存在显著差异（P〈0．01）,组间两两比较也存在显著差异（P〈0．05）。不同导联脑电信号第9尺度的相位平均波形的波长与简易智能精神状态量表（MMSE）评分之间存在负相关（P〈0．01）,说明这一参数与病情严重程度相关。结论：子波分析适用于痴呆病人脑电信号的定量分析,研究表明脑电信号的时频结构、多尺度功率谱分布和第9尺度相位平均波形的波长可以作为AD诊断和评估的定量电生理指标。     

振动对小鼠体内伊文氏篮分布的影响

在以往工作的基础上[1，2]，本文用药理学实验的方法对小鼠尾静脉注入伊文民蓝染料，在振动频率为20Hz，振幅为O．67mm与50Hz，0．44mm的条件下分别刚试了小鼠体内血液和腹腔渗出液中伊文氏蓝在0至2小时内的分布。结果表明：对于血液中伊文氏蓝浓度峰伍，两振动组均比对照组提前0．5小时；对于腹腔渗出液中伊文氏蓝浓度峰值，仅20Hz组比对照组提前0．5小时。从而证实了20Hz组与50Hz组可以改变血液中伊文氏蓝的分布。但是仅频率为20Hz，振幅为0.67mm的振动可以加快腹腔内毛细血管网处微血管内血液的流动。     

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.     

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 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.     

Non-invasive measurement of brain viscoelasticity using magnetic resonance elastography

The purpose of this work was to develop magnetic resonance elastography (MRE) for the fast and reproducible measurement of spatially averaged viscoelastic constants of living human brain. The technique was based on a phase-sensitive echo planar imaging acquisition. Motion encoding was orthogonal to the image plane and synchronized to intracranial shear vibrations at driving frequencies of 25 and 50 Hz induced by a head-rocker actuator. Ten time-resolved phase-difference wave images were recorded within 60 s and analyzed for shear stiffness and shear viscosity. Six healthy volunteers (six men; mean age 34.5 years; age range 25-44 years) underwent 23-39 follow-up MRE studies over a period of 6 months. Interindividual mean +/- SD shear moduli and shear viscosities were found to be 1.17 +/- 0.03 kPa and 3.1 +/- 0.4 Pas for 25 Hz and 1.56 +/- 0.07 kPa and 3.4 +/- 0.2 Pas for 50 Hz, respectively (P < or = 0.01). The intraindividual range of shear modulus data was 1.01-1.31 kPa (25 Hz) and 1.33-1.77 kPa (50 Hz). The observed modulus dispersion indicates a limited applicability of Voigt's model to explain viscoelastic behavior of brain parenchyma within the applied frequency range. The narrow distribution of data within small confidence intervals demonstrates excellent reproducibility of the experimental protocol. The results are necessary as reference data for future comparisons between healthy and pathological human brain viscoelastic data.     

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.     

Microvasculature alters the dispersion properties of shear waves – a multi‐frequency MR elastography study

Magnetic Resonance Elastography (MRE) uses macroscopic shear wave propagation to quantify mechanical properties of soft tissues. Micro‐obstacles are capable of affecting the macroscopic dispersion properties of shear waves. Since disease or therapy can change the mechanical integrity and organization of vascular structures, MRE should be able to sense these changes if blood vessels represent a source for wave scattering. To verify this, MRE was performed to quantify alteration of the shear wave speed c_s due to the presence of vascular outgrowths using an aortic ring model. Eighteen fragments of rat aorta included in a Matrigel matrix (n=6 without outgrowths, n=6 with a radial outgrowth extent of ~600µm and n=6 with ~850µm) were imaged using a 7 Tesla MR scanner (Bruker, PharmaScan). High resolution anatomical images were acquired in addition to multi‐frequency MRE (ν = 100, 115, 125, 135 and 150 Hz). Average c_s was measured within a ring of ~900µm thickness encompassing the aorta and were normalized to c_s0 of the corresponding Matrigel. The frequency dependence was fit to the power law model c_s ~ν^y. After scanning, optical microscopy was performed to visualize outgrowths. Results demonstrated that in presence of vascular outgrowths (1) normalized c_s significantly increased for the three highest frequencies (Kruskal‐Wallis test, P = 0.0002 at 125 Hz and P = 0.002 at 135 Hz and P = 0.003 at 150 Hz) but not for the two lowest (Kruskal‐Wallis test, P = 0.63 at 100 Hz and P = 0.87 at 115 Hz), and (2) normalized c_s followed a power law behavior not seen in absence of vascular outgrowths (ANOVA test, P < 0.0001). These results showed that vascular outgrowths acted as micro‐obstacles altering the dispersion relationships of propagating shear waves and that MRE could provide valuable information about microvascular changes. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

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.     

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.     

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.