磁共振弹性成像技术在肝纤维化检测中的研究

对肝脏组织的弹性应力分析在肝纤维化程度的精确定量评价方面是非常关键的,因此从弹性力学角度结合磁共振成像技术的磁共振弹性成像研究在肝脏疾病的早期诊断和治疗方面将具有重要意义和广泛应用. 该文针对弹性磁共振成像技术的理论与技术进行了全面的研究,开发了磁共振弹性图研究平台,主要包括：组织生物力学模型分析与建模,剪切波激励装置的开发,弹性成像序列的设计,弹性拟合算法研究与实现4个方面的工作. 基于上述工作,进行了相关体模和离体猪肝以及志愿者在体肝脏实验,实验结果表明,研究平台基本可以满足肝脏弹性成像研究的需要.     

基于双带宽高斯滤波器的磁共振弹性图局域频率估算算法研究与实现

本文对生物体软组织的生物力学模型进行了分析推导和简化,得到了磁共振相位图与生物组织弹性之间的力学关系,根据该关系研究了局域频率估算算法,应用Matlab对算法进行了编程实现,体模弹性图的实现验证了算法有效性,为后续开展临床肝纤维化分级研究奠定基础. 关键词： 磁共振弹性成像 弹性生物力学模型 局域频率估算     

基于聚焦光声层析技术的甲状腺离体组织成像

对人体甲状腺内的病变组织进行定位和成像对于准确诊断和有效治疗甲状腺疾病是至关重要的. 本文评估了利用光声层析技术对离体甲状腺组织进行成像的可行性, 并利用基于30 MHz超声换能器的聚焦光声成像系统对甲状腺进行扫描成像. 实验中成像系统的横向分辨率和纵向分辨率分别达到了350 μupm和74 μupm. 分别对正常离体甲状腺组织和模拟病变甲状腺组织进行光声成像. 实验结果表明, 本成像系统能够有效区分和鉴别正常甲状腺组织和病变组织. 此项技术有望进一步提高甲状腺疾病诊断的准确率, 以便更为有效地指导疾病的治疗, 具有潜在的临床应用前景.     

面向荧光剂药代动力学的动态扩散荧光层析系统

为捕捉生物组织体内快速变化的荧光信号,并借鉴扩散荧光层析在穿透深度、高灵敏度等方面的优势,设计了一套具备快速实时采样能力的动态扩散荧光层析成像在体测量系统.该系统采用多光源-探测器布配方案,结合光电倍增管探测器与锁相光子计数检测技术,具有高空间采样密度、高探测灵敏度、大动态测量范围以及高性价比等优势.有效性评估实验表明:该系统具备良好的稳定性和很强的环境光抑制能力,频率串扰率低于1.39%.仿体成像实验表明:该系统能够有效地对单个和多个目标体成像.活体健康小鼠吲哚菁绿肝代谢实验进一步表明:该系统可有效捕捉小鼠体内快速变化的荧光信号,能够用于荧光剂药代动力学研究.     

S波段微波热致超声成像系统研究

微波热致超声成像技术通过向物体发射微波脉冲, 导致物体吸收电磁波温度迅速升高, 产生瞬时压力波, 从而激发产生超声波信号, 通过传感器对产生的超声波信号进行采集并成像, 最终还原了反映物体吸收电磁波能量特性的图像, 由于此方法兼具了微波成像的高对比性和超声成像的高分辨率特点, 理论上验证了热声成像技术对早期乳腺肿瘤检测的可行性. 本实验兼顾系统成像深度和分辨率, 采用S波段的微波脉冲信号源对物体进行辐射, 利用圆形扫描方式对待测物体进行检测, 同时为了更好的验证成像性能, 本实验同时使用了肿瘤仿体及实际生物组织进行成像实验. 通过实验分析, 验证了该系统对肿瘤仿体和生物组织检测的有效性, 以及系统的高分辨率和高对比度特性, 为早期乳房肿瘤检测提供了进一步的理论支撑.     

超声动态向量血流成像的产品化实现

传统超声彩色多普勒成像测量的是血流沿超声传播方向上的速度分量,故无法得到垂直于超声传播方向的血流。向量血流成像是一种更加先进的超声血流成像技术。它不受角度限制,可以直接计算出血流速度的大小和方向。本文总结了现有多种超声向量血流成像技术的特点和发展情况,并从产品化实现的角度分析了各项技术的优缺点。从超声系统发射接收、血流成像、向量速度方向合成、显示等几个方面详述了迈瑞超声向量血流成像技术产品化实现过程中遇到的主要问题及解决方案。实验采用了中科院声学所研制的超声多普勒仿血流体模,通过向量血流成像和脉冲多普勒成像分别测量体模的仿血流速度。将向量血流成像直接计算出来的速度值与脉冲多普勒经过角度校正得到的速度进行对比。在不同条件下,经过多次测量,二者的平均相对误差均在10%以内。     

平面波经颅超声成像相位校正及散斑跟踪

准确的脑血流成像对脑功能监测和脑疾病的快速诊断具有重要意义,然而颅骨对超声传播的影响会导致成像质量下降、速度或位移估计不准确等问题.论文采用平面波相干复合结合散斑跟踪方法进行颅内散射目标成像和速度估计,以实现脑血流速度矢量检测;针对颅骨存在导致的超声相位畸变,利用数值仿真和体模实验研究了其对成像及散斑跟踪效果的影响,并...     

基于多层声速模型的合成孔径超声皮质骨成像

由于皮质骨和软组织间较大的声速差异,采用固定声速的传统超声波束形成方法无法重建皮质骨图像,同时皮质骨中较大的衰减也限制了信号信噪比.为了实现皮质骨超声成像,本文提出一种采用合成孔径超声提高成像分辨率及信噪比,利用压缩感知计算延时参数并构建多层声速模型的成像方法.本文结合时域有限差分仿真方法分析了理想情况下皮质骨成像结果,并结合软组织覆盖下的离体皮质骨板样本实验,验证相关方法的可行性.仿真和实验结果均表明,本文方法可用于构建多层声速模型并正确重建皮质骨图像.本研究实现了具有三层声速模型的皮质骨超声成像,对皮质骨超声成像发展有一定的借鉴意义,未来将进一步探索在体实验,以推进骨超声成像的临床应用.     

用于HIRFL重离子治癌的PET成像实验研究与蒙特卡罗模拟

为了HIRFL重离子治癌的需要,使用两个位置灵敏闪烁体探测器组成了一个简单的PET成像系统.对PET成像进行了实验研究,实验测量得到了物体成像以及γ射线能谱,对于511keV全能峰处的能量分辨率为186%,峰总比为52.4%.采用GEANT3程序对该系统进行了模拟计算,并与实验进行比较,最后对该系统进行了优化设计     

纵向带状裂隙形貌的逆时偏移超声成像

传统的工业超声成像方法通常只能确定缺陷的位置与横向尺寸,无法获得缺陷的形貌信息.一些特殊的缺陷,如纵向裂纹,是典型的例子.基于多阵元技术,开展了固体介质缺陷逆时偏移超声成像方法的数值与实验研究.针对铝块平底纵裂纹及内部纵裂纹两种传统方法无法有效成像的缺陷,首先开展了单分量逆时偏移成像方法研究,给出了基于数值仿真的逆时偏移成像结果以及基于多阵元超声成像实验系统实验测试的逆时偏移成像结果.进一步开展了基于多分量位移检测与转换横波分离的逆时偏移成像方法研究,并提出了基于新型多分量激光干涉仪进行检测的思路.数值仿真结果证实了多分量逆时偏移图像重建结果可以克服单分量方式的缺点,得到明显优于单分量检测时的图像.     

Rapid acquisition technique for MR elastography of the liver

Magnetic resonance elastography (MRE) of the liver is a novel noninvasive clinical diagnostic tool to stage fibrosis based on measured stiffness. The purpose of this study is to design, evaluate and validate a rapid MRE acquisition technique for noninvasively quantitating liver stiffness which reduces by half the scan time, thereby decreasing image registration errors between four MRE phase offsets. In vivo liver MRE was performed on 16 healthy volunteers and 14 patients with biopsy-proven liver fibrosis using the standard clinical gradient recalled echo (GRE) MRE sequence (MREs) and a developed rapid GRE MRE sequence (MREr) to obtain the mean stiffness in an axial slice. The mean stiffness values obtained from the entire group using MREs and MREr were 2.72 ± 0.85 kPa and 2.7 ± 0.85 kPa, respectively, representing an insignificant difference. A linear correlation of R² = 0.99 was determined between stiffness values obtained using MREs and MREr. Therefore, we can conclude that MREr can replace MREs, which reduces the scan time to half of that of the current standard acquisition (MREs), which will facilitate MRE imaging in patients with inability to hold their breath for long periods.     

Quantitative MRI of the liver: Evaluation of extracellular volume fraction and other quantitative parameters in comparison to MR elastography for the assessment of hepatopathy

BackgroundChronic liver diseases pose a major health problem worldwide, while common tests for diagnosis and monitoring of diffuse hepatopathy have considerable limitations. Preliminary data on the quantification of hepatic extracellular volume fraction (ECV) with magnetic resonance imaging (MRI) for non-invasive assessment of liver fibrosis are encouraging, with ECV having the potential to overcome several of these constraints.PurposeTo clinically evaluate ECV provided by quantitative MRI for assessing the severity of liver disease.Materials and methodsIn this prospective study, multiparametric liver MRI, including T1 mapping and magnetic resonance elastography (MRE), was performed in subjects with and without hepatopathy between November 2018 and October 2019. T1, T2, T2*, proton density fat fraction and stiffness were extracted from parametric maps by regions of interest and ECV was calculated from T1 relaxometries. Serum markers of liver disease were obtained by clinical database research. For correlation analysis, Spearman rank correlation was used. ROC analysis of serum markers and quantitative MRI data for discrimination of liver cirrhosis was performed with MRE as reference standard.Results109 participants were enrolled (50.7 ± 16.1 years, 61 men). ECV, T1 and MRE correlated significantly with almost all serum markers of liver disease, with ECV showing the strongest associations (up to r = 0.67 with MELD, p < 0.01). ECV and T1 correlated with MRE (0.75 and 0.73, p < 0.01 each). ECV (AUC 0.89, cutoff 32.2%, sensitivity 85%, specificity 87%) and T1 mapping (AUC 0.85, cutoff 592.5 ms, sensitivity 83%, specificity 75%) featured good performances in detection of liver cirrhosis with only ECV performing significantly superior to model of end stage liver disease (MELD), AST/ALT ratio and international normalized ratio (p < 0.01, respectively).ConclusionQuantification of hepatic extracellular volume fraction with MRI is suitable for estimating the severity of liver disease when using MRE as the standard of reference. It represents a promising tool for non-invasive assessment of liver fibrosis and cirrhosis.     

Static and dynamic liver stiffness: An ex vivo porcine liver study using MR elastography

Magnetic resonance elastography (MRE) is an MRI-based noninvasive technique for quantitatively assessing tissue stiffness. The hypothesis of this study is that stiffness increases with portal pressure. We further hypothesized that the rate of stiffness change with pressure would be larger in liver tissue treated to simulate the stiffening effects of fibrosis. In agreement with our hypothesis, the formalin-treated livers were stiffer than the untreated livers, and in both groups the liver stiffness increased with portal venous pressure. The rate of stiffness change with portal pressure was significantly greater after formalin treatment. In this study, we have developed an ex vivo liver model incorporating portal venous pressure variations and observed significant changes in liver stiffness due to portal pressure. This model could be useful for understanding and investigating the changes in the static and dynamic components of liver stiffness.     

Simulation and analysis of magnetic resonance elastography wave images using coupled harmonic oscillators and Gaussian local frequency estimation.

New methods for simulating and analyzing Magnetic Resonance Elastography (MRE) images are introduced. To simulate a two-dimensional shear wave pattern, the wave equation is solved for a field of coupled harmonic oscillators with spatially varying coupling and damping coefficients in the presence of an external force. The spatial distribution of the coupling and the damping constants are derived from an MR image of the investigated object. To validate the simulation as well as to derive the elasticity modules from experimental MRE images, the wave patterns are analyzed using a Local Frequency Estimation (LFE) algorithm based on Gauss filter functions with variable bandwidths. The algorithms are tested using an Agar gel phantom with spatially varying elasticity constants. Simulated wave patterns and LFE results show a high agreement with experimental data. Furthermore, brain images with estimated elasticities for gray and white matter as well as for exemplary tumor tissue are used to simulate experimental MRE data. The calculations show that already small distributions of pathologically changed brain tissue should be detectable by MRE even within the limit of relatively low shear wave excitation frequency around 0.2 kHz.     

Effect of off-frequency sampling in magnetic resonance elastography

In magnetic resonance elastography (MRE), shear waves at a certain frequency are encoded through bipolar gradients that switch polarity at a controlled encoding frequency and are offset in time to capture wave propagation using a controlled sampling frequency. In brain MRE, there is a possibility that the mechanical actuation frequency is different from the vibration frequency, leading to a mismatch with encoding and sampling frequencies. This mismatch can occur in brain MRE from causes both extrinsic and intrinsic to the brain, such as scanner bed vibrations or active damping in the head. The purpose of this work was to investigate how frequency mismatch can affect MRE shear stiffness measurements. Experiments were performed on a dual-medium agarose gel phantom, and the results were compared with numerical simulations to quantify these effects. It is known that off-frequency encoding alone results in a scaling of wave amplitude, and it is shown here that off-frequency sampling can result in two main effects: (1) errors in the overall shear stiffness estimate of the material on the global scale and (2) local variations appearing as stiffer and softer structures in the material. For small differences in frequency, it was found that measured global stiffness of the brain could theoretically vary by up to 12.5% relative to actual stiffness with local variations of up to 3.7% of the mean stiffness. It was demonstrated that performing MRE experiments at a frequency other than that of tissue vibration can lead to artifacts in the MRE stiffness images, and this mismatch could explain some of the large-scale scatter of stiffness data or lack of repeatability reported in the brain MRE literature.     

Magnetic resonance elastography using an air ball-actuator

The purpose of this study was to develop a new technique for a powerful compact MR elastography (MRE) actuator based on a pneumatic ball-vibrator. This is a compact actuator that generates powerful centrifugal force vibrations via high speed revolutions of an internal ball using compressed air. This equipment is easy to handle due to its simple principles and structure. Vibration frequency and centrifugal force are freely adjustable via air pressure changes (air flow volume), and replacement of the internal ball. In order to achieve MRI compatibility, all parts were constructed from non-ferromagnetic materials. Vibration amplitudes (displacements) were measured optically by a laser displacement sensor. From a bench test of displacement, even though the vibration frequency increased, the amount of displacement did not decrease. An essential step in MRE is the generation of mechanical waves within tissue via an actuator, and MRE sequences are synchronized to several phase offsets of vibration. In this system, the phase offset was detected by a four-channel optical-fiber sensor, and it was used as an MRI trigger signal. In an agarose gel phantom experiment, this actuator was used to make an MR elastogram. This study shows that the use of a ball actuator for MRE is feasible.     

Staging liver fibrosis by using liver-enhancement ratio of gadoxetic acid-enhanced MR imaging: comparison with aspartate aminotransferase-to-platelet ratio index

Objective

To compare the diagnostic ability of gadoxetic acid-enhanced hepatocyte-phase MR images with aspartate aminotransferase-to-platelet ratio index (APRI) to predict liver fibrosis stage.

Materials and Methods

Our study included 100 patients who underwent gadoxetic acid-enhanced MRI and either liver biopsy or liver surgery. Liver fibrosis stage was histologically determined according to the METAVIR system: F0 (n=16), F1 (n=17), F2 (n=10), F3 (n=21) and F4 (n=36). Four measures were used as imaging-based fibrosis markers: liver-spleen contrast ratio, liver-enhancement ratio, corrected liver-enhancement ratio and spleen index. APRI represented a blood test-based fibrosis marker. The diagnostic ability of those fibrosis markers were compared through receiver-operating characteristic analysis.

Results

The area under the curve (AUC) for APRI prediction of severe fibrosis (≥F3 and F4) was significantly greater than that of corrected liver-enhancement ratio. However, corrected liver-enhancement ratio had a greater AUC for prediction of mild fibrosis (≥F1) than APRI, although the difference was insignificant.

Conclusion

Corrected liver-enhancement ratio with gadoxetic acid-enhanced MRI is correlated to the stage of liver fibrosis. APRI, however, has greater reliability for predicting severe fibrosis and cirrhosis than does the imaging-based fibrosis marker tested in this study.     

Magnetic resonance elastography of the brain in a mouse model of Alzheimer's disease: initial results

The increasing prevalence of Alzheimer's disease (AD) has provided motivation for developing novel methods for assessing the disease and the effects of potential treatments. Magnetic resonance elastography (MRE) is an MRI-based method for quantitatively imaging the shear tissue stiffness in vivo. The objective of this research was to determine whether this new imaging biomarker has potential for characterizing neurodegenerative disease. Methods were developed and tested for applying MRE to evaluate the mouse brain, using a conventional large bore 3.0T MRI system. The technique was then applied to study APP-PS1 mice, a well-characterized model of AD. Five APP-PS1 mice and 8 age-matched wild-type mice were imaged immediately following sacrifice. Brain shear stiffness measurements in APP-PS1 mice averaged 22.5% lower than those for wild-type mice (P = .0031). The results indicate that mouse brain MRE is feasible at 3.0T, and brain shear stiffness has merit for further investigation as a potential new biomarker for Alzheimer's disease.     

Feasibility of fast MR imaging of the liver at 1.5 T

A phantom with T1 and T2 relaxation times encompassing normal liver and liver lesions was constructed to evaluate fast magnetic resonance pulse sequences using TR from 21-100 milliseconds, TE 12-60 milliseconds and flip angles from 5 degrees-90 degrees. Ten of these fast MR sequences were then selected and compared with conventional spin-echo sequences in normal volunteers (n = 3) and in patients with liver lesions (n = 6). Subjectively, the fast MR sequences eliminated motion artefacts. Objectively, 8 of 10 fast sequences had signal-to-noise ratios comparable to spin-echo imaging whereas only 2 of 10 had contrast-to-noise ratios that were similar to spin-echo imaging. This preliminary study, performed at 1.5 Tesla, does not show any clear-cut advantage of fast imaging over spin-echo imaging in the detection of liver lesions. The use of a liver tissue equivalent phantom provides a rapid, practical approach in evaluation of fast scans.