Intravascular ultrasound elastography: an overview

The composition and morphology of the atherosclerotic lesion are currently considered more important determinants of acute coronary ischemic syndromes than the degree of stenosis. When a lesion is unstable, it may rupture and cause an acute thrombotic reaction. A rupture prone plaque contains a large lipid pool covered by a thin fibrous cap. The stress in the cap increased with decreasing thickness. Additionally, it may be weakened by macrophage infiltration. Intravascular ultrasound elastography might be an ideal technique to assess the presence of lipid pools and identify high stress regions. Elastography is a technique to assess local mechanical properties of tissue. The underlying principle is that the deformation of tissue by a mechanical excitation is a function of its mechanical properties. The deformation of the tissue is determined using ultrasound. For intravascular purposes, the intraluminal pressure is used as the excitation force. The radial strain in the tissue is obtained by cross-correlation techniques on the radio frequency (rf) signal. The strain is colour-coded and plotted as a complimentary image to the IVUS echogram. Elastography was validated in vitro using diseased human coronary and femoral arteries. After the ultrasound experiments, the specimens were processed for routine histology to counterstain collagen, smooth-muscle cells, and macrophage activity. Regions were segmented in the elastograms based on their strain values. Next, the dominant plaque type (fibrous, fibro-fatty or fatty) was defined by observers blinded to the elastographic result. These experiments demonstrate that the strain in the three plaque types is different (Kruskall-Wallis p < 0.001). Especially between fibrous and fatty tissue, a highly significant difference (Wilcoxon p < 0.001) was found. In vivo, the technique is validated in an atherosclerotic Yucatan mini-pig animal model. High-resolution echo frames (30 frames per second) were acquired near end-diastole. In this phase of the pressure cycle, catheter motion was minimal. Frames with a pressure difference of approx. 5 mm Hg were taken to determine the elastograms. This in vivo validation study in Yucatan mini-pigs revealed higher strain values in fatty material (ANOVA p < 0.001). All cross-sections with a fatty plaque were identified with the elastogram by the presence of high strain values. Additionally, data are acquired in patients referred for Percutaneous Transluminal Coronary Angioplasty with the same set-up as tested in the animal study. Ultrasound data of soft, fibrous, calcified and stented plaques are acquired near end-diastole. The elastogram of soft plaques. as identified from the deformation during the pressure cycle, reveals strain values of 1% with increased strain up to 2% at the shoulders of the plaque. Calcified material, as identified from the echogram, shows low strain values of 0-0.2%. The elastogram of stented plaques reveals very low strain values, except for two regions: these are between the stent struts and at the shoulders of the plaque. In conclusion, intravascular elastography appears to be a unique tool to determine local mechanical properties in atherosclerotic lesions to identify fibrous and fatty tissue. Experiments have demonstrated the feasibility of this technique to be applied in vivo.     

Vascular tissue characterisation with IVUS elastography

Knowledge about the mechanical properties of the vessel wall and plaque is important for guiding intravascular interventional procedures and detection of plaque vulnerability. Rupture of atherosclerotic plaques is associated with acute myocardial infarction and unstable angina pectoris. In a plaque with a lipid core, the stress due to the arterial pulsation will be concentrated in the cap and a thin cap may be unable to bear this stress. In this study, the potential of intravascular elastography to characterise fibrous, fibro-fatty and fatty tissue based on their mechanical properties was investigated. Using a custom-made set-up, intravascular echograms and elastograms of excised human femoral arteries were determined. High frequency r.f. data (30 MHz) were acquired using an intravascular catheter. The tissue was compressed using intravascular pressures of 80 and 100 mmHg. The cross-sections of interest were marked with a needle for matching with histology. Using cross-correlation estimation of gated echosignals, elastograms (images of the local strain) were determined. After the intravascular experiments, the specimens were fixed in formaldehyde and processed for paraffin embedding. Sections were stained with picrosirius red and alpha-actin to counterstain collagen and smooth muscle cells (SMC), respectively. Results of vessel cross-sections with fibrous and fatty plaque regions will be presented. The elastograms of these specimens show that the strain in fatty tissue is higher than the strain in fibrous material. In conclusion, these in vitro experiments on human femoral arteries indicate the potential of intravascular elastography to characterise different plaque components.     

Behavior of Atherosclerotic Plaque Components After in Vitro Angioplasty and Atherectomy Studied by High Field MR Imaging

Aims: Using magnetic resonance imaging (MRI), we developed in vitro models to image the response of fatty, fibrous, and calcified plaques to in vitro models of angioplasty and atherectomy, and tested the resistance of collagenous cap and lipid core to radial compression. Methods and Results: We studied the effects of balloon compression on 10 fibrous plaques with a complete collagenous cap (group A), 6 fatty plaques without cap (group B), and 5 calcified plaques (group C). Atherectomy was performed on nine other fibrous lesions (group D). In group A, fibrous cap, lipid core, and plaque did not change after radial compression despite a decrease in luminal obstruction due to medial stretching. In group B, a reduction of plaque (−30%) and lipid core (−35%) were observed. Compression dissected calcified plaques at the shoulder level. In group D, atherectomy reduced collagenous cap by 54%, and plaque by 35%. Conclusions: In these models, MRI shows 1) the high resistance of collagenous caps to radial compression, 2) a stretching effect of compression on disease-free walls, enlarging lumen in case of fibrous plaque, but a reduction and redistribution of lipid cores in case of fatty plaques, 3) the rupture of calcified arteries at the plaque shoulder, and 4) the reduction of fibrous components by atherectomy but not by angioplasty. By characterizing plaque composition, MRI may allow a predictable response of atherosclerotic arteries to interventional procedures.     

Tissue velocity imaging of coronary artery by rotating-type intravascular ultrasound

Intravascular ultrasound (IVUS) provides not only the dimensions of coronary artery but the information of tissue components. In catheterization laboratory, soft and hard plaques are classified by visual inspection of echo intensity. So-called soft plaque contains lipid core or thrombus and it is believed to be more vulnerable than a hard plaque. However, it is not simple to analyze the echo signals quantitatively. When we look at a reflection signal, the intensity is affected by the distance of the object, the medium between transducer and objects and the fluctuation caused by rotation of IVUS probe. The time of flight is also affected by the sound speed of the medium and Doppler shift caused by tissue motion but usually those can be neglected. Thus, the analysis of RF signal in time domain can be more quantitative than intensity of RF signal. In the present study, a novel imaging technique called "intravascular tissue velocity imaging" was developed for searching a vulnerable plaque. Radio-frequency (RF) signal from a clinically used IVUS apparatus was digitized at 500 MSa/s and stored in a workstation. First, non-uniform rotation was corrected by maximizing the correlation coefficient of circumferential RF signal distribution in two consecutive frames. Then, the correlation and displacement were calculated by analyzing the radial difference of RF signal. Tissue velocity was determined by the displacement and the frame rate. The correlation image of normal and atherosclerotic coronary arteries clearly showed the internal and external borders of arterial wall. Soft plaque with low echo area in the intima showed high velocity while the calcified lesion showed the very low tissue velocity. This technique provides important information on tissue character of coronary artery.     

Effect of temperature increase and freezing on intravascular elastography

Intravascular ultrasound (IVUS) elastography is a technique that assesses the local strain in the vessel wall and plaque. The strain is an important parameter for characterization of different plaque components. These regions are related to plaque vulnerability. IVUS elastography was validated in vitro using human coronary and femoral arteries. These experiments were performed on specimens that were stored frozen and measured at room temperature for practical issues. The aim of this study is to determine the influence of freezing and measuring the tissues at room temperature (23 degrees C instead of 37 degrees C) on the elastic properties. Four human coronary, one carotid and one femoral arteries were first measured at 23 degrees C and next at 37 degrees C. Additionally they were stored at -80 degrees C for up to 24 h and finally measured at 23 degrees C. Acquisitions at intraluminal pressures of 80 and 100 mmHg were performed using an EndoSonics 20 MHz Visions catheter. Elastograms were determined from the IVUS rf-data (sampled at 100 MHz in 12 bits) that were obtained from a digital interface. Qualitative and quantitative analysis of the elastograms obtained from fresh and frozen specimens measured at 23 degrees C reveals that storage of the specimen at -80 degrees C has no significant influence. In vitro experiments can be performed at room temperature after storage of the tissue at -80 degrees C without significant affection of the information with respect to measuring fresh ex vivo material at body temperature.     

Ultrasonic elastography using sector scan imaging and a radial compression

Elastography is an imaging technique based on strain estimation in soft tissues under quasi-static compression. The stress is usually created by a compression plate, and the target is imaged by an ultrasonic linear array. This configuration is used for breast elastography, and has been investigated both theoretically and experimentally. Phenomena such as strain decay with tissue depth and strain concentrations have been reported. However in some in vivo situations, like prostate or blood vessels imaging, this set-up cannot be used. We propose a device to acquire in vivo elastograms of the prostate. The compression is applied by inflating a balloon that covers a transrectal sector probe. The 1D algorithm used to calculate the radial strain fails if the center of the imaging probe does not correspond to the center of the compressor. Therefore, experimental elastograms are calculated with a 2D algorithm that accounts for tangential displacements of the tissue. In this article, in order to gain a better understanding of the image formation process, the use of ultrasonic sector scans to image the radial compression of a target is investigated. Elastograms of homogeneous phantoms are presented, and compared with simulated images. Both show a strain decay with tissue depth. Then experimental and simulated elastograms of a phantom that contains a hard inclusion are presented, showing that strain concentrations occur as well. A method to compensate for strain decay and therefore to increase the contrast of the strain elastograms is proposed. It is expected that such information will help to interpret and possibly improve the elastograms obtained via radial compression.     

利用高翅管换热器提高压力恢复系统效率

为提高压力恢复系统效率,设计并制造了一台高翅管换热器。采用滚扎而成的整体式螺旋高翅片管,代替套片式圆形普通翅片管,翅片管材料为紫铜,管束按等腰三角形叉排布置,管内强制水冷。测试了高翅管换热器的阻力特性,对比分析了加入换热器前后压力恢复系统性能的变化。结果表明:随着背压的提高,该换热器流阻逐渐降低,当背压达到9.366kPa时,换热器流阻为0.133kPa,仅占换热器入口激光尾气压力的1.4%;与不加换热器相比,加入高翅管换热器后的引射器混合室入口压力降低了12.95%,压力恢复系统的效率得到了提高。     

Intravascular photoacoustic imaging of lipid in atherosclerotic plaques in the presence of luminal blood

Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.     

Finite element formulation of the first- and second-order discrete ordinates equations for radiative heat transfer calculation in three-dimensional participating media

Two finite element methods (FEMs), FEDOM1 and FEDOM2 (standing for the first and the second finite element discrete ordinates methods, respectively), are formulated and numerically tested. The reference second-order discrete equation is modified in its scattering terms and is applied to the problems of absorbing/emitting and anisotropically scattering media by using the FEM. Numerical features of the developed FEMs are compared with one of the discrete ordinates interpolation method (DOIM), which uses a finite difference scheme. Prediction results of radiative heat transfer by these two FEMs are compared with reference solutions and verified in three-dimensional enclosures containing participating media. The results of FEDOM1 and FEDOM2 agree well with exact solutions for the problem of absorbing/emitting medium with various range of optical thickness. Generally, the two FEMs show more accurate results than DOIM. And FEDOM1 shows more accurate results than FEDOM2 in most of the test problems. Both of the developed FEMs show reasonable results compared with published Monte Carlo solutions for the tested absorbing/emitting and anisotropically scattering media. Although the FEDOM2 is not as accurate as the FEDOM1, it shows its own advantages that it reduces CPU time and memory space of dependent variable to half.     

Intravascular two-dimensional tissue strain imaging

Our goal is to achieve the precise quantitative imaging of tissue elasticity in clinical settings. In the present study, we measured basic ultrasonic characteristics of atherosclerosis by two-dimensional (2D) intravascular tissue velocity imaging. Radio-frequency (RF) signal from a clinically used IVUS apparatus was digitized at 500 MSa/s and stored in a workstation. First, the correlation coefficient between two consecutive frames was calculated in the rotational direction and the rotational disuniformity was corrected to obtain the maximum correlation coefficient. Then, the polar coordinate images were converted into rectangular coordinate images and the images were divided into 64 by 64 square shaped regions of interest (ROIs). The correlation and displacement of the ROIs between the consecutive two frames were calculated by template matching method. Two-dimensional tissue velocity was defined as the vectors of displacement of ROI with 0.7 and more correlation. IVUS studies were performed in directional coronary atherectomy (DCA) procedures. The specimens excised by DCA were stained with Elastica-Masson's trichrome staining and CD68 immunochemical staining. Eleven cases (including two no re-flow cases and one perforation case) were intraoperatively observed by IVUS and the specimens obtained by DCA were observed by optical microscopy. The specimen from homogeneous 2D strain was collagen dominant fibrosis and the specimen from a lesion with complex vectors contained CD68 positive cells and degenerated collagen fibers, which indicated the plaque was vulnerable.     

In vivo attenuation and equivalent scatterer size parameters for atherosclerotic carotid plaque: Preliminary results

We have previously reported on the equivalent scatterer size, attenuation coefficient, and axial strain properties of atherosclerotic plaque ex vivo. Since plaque structure and composition may be damaged during a carotid endarterectomy procedure, characterization of in vivo properties of atherosclerotic plaque is essential. The relatively shallow depth of the carotid artery and plaque enables non-invasive evaluation of carotid plaque utilizing high frequency linear-array transducers. We investigate the ability of the attenuation coefficient and equivalent scatterer size parameters to differentiate between calcified, and lipidic plaque tissue. Softer plaques especially lipid rich and those with a thin fibrous cap are more prone to rupture and can be classified as unstable or vulnerable plaque. Preliminary results were obtained from 10 human patients whose carotid artery was scanned in vivo to evaluate atherosclerotic plaque prior to a carotid endarterectomy procedure. Our results indicate that the equivalent scatterer size obtained using Faran’s scattering theory for calcified regions are in the 120–180 μm range while softer regions have larger equivalent scatterer size distribution in the 280–470 μm range. The attenuation coefficient for calcified regions as expected is significantly higher than that for softer regions. In the frequency bandwidth ranging from 2.5 to 7.5 MHz, the attenuation coefficient for calcified regions lies between 1.4 and 2.5 dB/cm/MHz, while that for softer regions lies between 0.3 and 1.3 dB/cm/MHz.     

Mechanical model of vulnerable atherosclerotic plaque rupture

Atherosclerotic vascular disease is the most common cause of morbidity and mortality in the world. Until quite recently, it has been generally thought that the accretion of atherosclerotic plaque in coronary arteries progressively occluded the arterial lumen, resulting in a decrease in coronary blood flow reserve and ultimately producing myocardial ischemia, and the therapeutic aim to atherosclerosis has mainly focused on reducing the plaque. However, evidence accumulated over recent years has…     

Generation of a spatially coherent field structure in free-electron masers with 2D distributed feedback

Nonlinear dynamics of free-electron masers (FEMs) is studied in the planar geometry with 2D distributed feedback (DFB). As is distinct from previous works, the field structure is not fixed with respect to the three spatial coordinates including the coordinate that is orthogonal to surfaces of the plates of the 2D Bragg resonator. Conditions on the allowed oversize parameter (ratio of the gap between the resonator plates to wavelength) under which the steady-state generation remains stable upon variation in electron-beam parameters are derived. It is demonstrated that, at a relatively large gap, variations in the mismatch lead to the jumps of oscillation frequency that correspond to the excitation of bunches of modes with different transverse indices of partial waves. The results of simulation using a particle-in-cell method are presented for a FEM prototype with 2D DFB that is created using an ELMI accelerator at the Institute of Nuclear Physics, Siberian Branch, Russian Academy of Sciences. The simulated results show that narrow-band spatially coherent radiation can be generated at experimental parameters of the electron beam and electrodynamic system. The advantages of 2D Bragg structures in comparison with conventional 1D structures are demonstrated for FEMs.     

Design and modeling of microwave photonic devices

Different types of finite element methods (FEMs) for microwave and optical waveguides are reviewed and are utilized for modeling of a traveling-wave (TW) optical modulator, as one of the typical microwave photonic devices. Using the quasi-TEM and the full-wave vector FEM solvers for microwave waveguides and the scalar FEM solver for optical waveguides, the behaviour of a TW Z-cut Ti:LiNbO3 Mach–Zehnder optical modulator with a ridge structure is investigated.     

Ultrasonic speed microscopy for imaging of coronary artery

We have been developing a scanning acoustic microscope (SAM) system for medicine and biology featuring quantitative measurement of ultrasonic speed and attenuation of soft tissues. In the present study, we will propose a new concept ultrasonic speed microscopy that can measure the thickness and ultrasonic speed using fast Fourier transform of a single pulsed wave instead of continuous waves used in conventional SAM systems. Six coronary arteries were frozen and sectioned approximately 10 microm in thickness. They were mounted on glass slides without cover slips. The scanning time of a frame with 300 x 300 pixels was 121 s and two-dimensional distribution of ultrasonic speed was obtained. The ultrasonic speed was 1720 m/s in the thickened intima with collagen fiber, 1520 m/s in lipid deposition underlying fibrous cap and 1830 m/s in calcified lesion in the intima. These basic measurements will help understanding echogenecity in intravascular ultrasound (IVUS) images. Imaging of coronary artery with the ultrasonic speed microscopy provides important information for study of IVUS coronary imaging.     

On Applicability of a Direct Shear Test for Strength Estimation of Cereal Grain

Investigations were performed to verify the applicability of a direct shear method as recommended by Eurocode 1 for testing the strength of cereal grains [2]. Tests on rye without preconsolidation have shown that stress‐strain characteristics depend on the method of sample deposition. However, consolidation of the sample by twisting the top plate, as recommended by the code, neutralizes the influence of the grain packing structure on values of the angle of internal friction. Determination of the strength parameters for grain of six genera, under normal reference pressure of 100 kPa, and five levels of moisture content in a range from 10% to 20%, confirmed the applicability of the test. The only necessary modification of Eurocode procedure was elongation of the shear path up to the 0.1 ΔL/D level of the sample diameter. Values for the angle of internal friction were found to range from 22.1°–35.5° and were dependent on the grain genus and moisture content. The majority of dry grain samples showed low cohesion (below 4 kPa), and thus, should be treated as free flowing material. The increase in moisture content resulted in an increase of cohesion up to the highest observed value of 12 kPa. Triaxial compression tests were performed on wheat of five levels of moisture content, and gave results that were in close agreement with the results of the direct shear test.     

Si/SiGe异质结构的硅盖层中应变对Raman谱特征的影响

应变Si/SiGe异质结构通过大剂量Ge离子注入并结合高温快速热退火制备而成。325 nm波长的紫外激光被用于调查应变Si盖层的Raman谱特征。实验发现,硅盖层中的张应变导致硅的520 cm-1的一级拉曼散射峰向低频方向偏移,峰的偏移程度反映硅盖层中横向张应力的大小约为12.5×108 N·m-2。硅盖层中的张应变并未导致1 555和2 330 cm-1的次级拉曼散射峰的变化。     

Effects of gadoxetic acid on liver elasticity measurement by using magnetic resonance elastography

The purpose of this study was to evaluate the effect of gadoxetic acid (Gd-EOB-DTPA) on measurements of liver stiffness by using magnetic resonance elastography (MRE). In this study, 104 consecutive patients (mean age, 67.7±9.4 years) underwent MRE using a 1.5-T MR scanner equipped with a cylindrical passive driver that was placed across the right chest wall for delivering vibrations. Axial gradient-echo images, which were automatically converted to elastograms that represented stiffness (kPa), were acquired using a continuous sinusoidal vibration of 60 Hz. Two raters independently placed a region of interest on the right lobe of the liver on the elastograms obtained before and after Gd-EOB-DTPA was administered. Liver stiffness was measured using these two elastograms and compared using a paired t test and correlation analysis. No significant difference was observed in liver stiffness before and after Gd-EOB-DTPA was administered (Rater 1, P=.1200; Rater 2, P=.3585). The correlation coefficients were 0.986 (Rater 1) and 0.984 (Rater 2), indicating excellent correlation between the stiffness values before and after Gd-EOB-DTPA was administered. Liver stiffness measured by MRE did not differ before and after Gd-EOB-DTPA was administered.     

Ex vivo study of carotid endarterectomy specimens: quantitative relaxation times within atherosclerotic plaque tissues

Purpose

Previous studies reporting relaxation times within atherosclerotic plaque have typically used dedicated small-bore high-field systems and small sample sizes. This study reports quantitative T₁, T₂ and T₂^? relaxation times within plaque tissue at 1.5 T using spatially co-matched histology to determine tissue constituents.

Methods

Ten carotid endarterectomy specimens were removed from patients with advanced atherosclerosis. Imaging was performed on a 1.5-T whole-body scanner using a custom built 10-mm diameter receive-only solenoid coil. A protocol was defined to allow subsequent computation of T₁, T₂ and T₂^? relaxation times using multi-flip angle spoiled gradient echo, multi-echo fast spin echo and multi-echo gradient echo sequences, respectively. The specimens were subsequently processed for histology and individually sectioned into 2-mm blocks to allow subsequent co-registration. Each imaging sequence was imported into in-house software and displayed alongside the digitized histology sections. Regions of interest were defined to demarcate fibrous cap, connective tissue and lipid/necrotic core at matched slice-locations. Relaxation times were calculated using Levenberg-Marquardt's least squares curve fitting algorithm. A linear-mixed effect model was applied to account for multiple measurements from the same patient and establish if there was a statistically significant difference between the plaque tissue constituents.

Results

T₂ and T₂^? relaxation times were statistically different between all plaque tissues (P=.026 and P=.002 respectively) [T₂: lipid/necrotic core was lower 47±13.7 ms than connective tissue (67±22.5 ms) and fibrous cap (60±13.2 ms); T₂^?: fibrous cap was higher (48±15.5ms) than connective tissue (19±10.6 ms) and lipid/necrotic core (24±8.2 ms)]. T₁ relaxation times were not significantly different (P=.287) [T₁: Fibrous cap: 933±271.9 ms; connective tissue (1002±272.9 ms) and lipid/necrotic core (1044±304.0 ms)]. We were unable to demarcate hemorrhage and calcium following histology processing.

Conclusions

This study demonstrates that there is a significant difference between qT₂ and qT₂^? in plaque tissues types. Derivation of quantitative relaxation times shows promise for determining plaque tissue constituents.     

Carotid plaque high-resolution MRI at 3 T: evaluation of a new imaging score for symptomatic plaque assessment

Purpose

To assess the sensitivity and specificity of intra-plaque hemorrhage (IPH), large lipid-rich necrotic core (LR-NC) and ulceration or cap rupture (UCR) for symptomatic carotid plaque characterization and to evaluate a new imaging score [Hemorrhage, Ulceration or cap rupture, Lipid-rich necrotic Core (HULC) score based on the sum of presence/absence of IPH, UCR and LR-NC; range 0–3] for assessment of recently symptomatic carotid plaques.

Material and methods

Twenty-seven recently symptomatic (< 8 weeks) and 36 asymptomatic patients with a carotid plaque thicker than 2 mm were prospectively imaged on a 3-T magnetic resonance (MR) system using high-resolution, multi-contrast MR sequences. Prior to analysis, all images were reviewed to assess image quality of each sequence. Sensitivity and specificity of IPH, LR-NC, UCR and HULC scores were calculated.

Results

Fifty-one patients were analyzed (26 symptomatic carotids and 67 asymptomatic carotids) after exclusion of studies with poor image quality. Sensitivity and specificity for symptomatic carotid plaque was, respectively, 46.1% and 97% for IPH, 84.6% and 73.1% for UCR and 80.7% and 76.1% for LR-NC. A HULC score of 2 or more showed a sensitivity of 73% and a specificity of 92.5%.

Conclusion

At 3 T, intra-plaque hemorrhage is the most specific criterion to characterize symptomatic carotid plaque. The HULC score offers the best compromise between sensitivity and specificity.