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.     

Finite element modeling and intravascular ultrasound elastography of vulnerable plaques: parameter variation

BACKGROUND AND GOAL: More than 60% of all myocardial infarction is caused by rupture of a vulnerable plaque. A vulnerable plaque can be described as a large, soft lipid pool covered by a thin fibrous cap. Plaque material composition, geometry, and inflammation caused by infiltration of macrophages are considered as major determinants for plaque rupture. For diagnostic purposes, these determinants may be obtained from elastograms (i.e. radial strain images), which are derived from intravascular ultrasound (IVUS) measurements. IVUS elastograms, however, cannot be interpreted directly as tissue component images, because radial strain depends upon plaque geometry, plaque material properties, and used catheter position. To understand and quantify the influence of these parameters upon measured IVUS elastograms, they were varied in a finite element model (FEM) that simulates IVUS elastograms of vulnerable plaques. MATERIALS AND METHODS: IVUS elastography measurements were performed on a vessel mimicking phantom, with a soft plaque embedded in a hard wall, and an atherosclerotic human coronary artery containing a vulnerable plaque. Next, FEMs were created to simulate IVUS elastograms of the same objects. In these FEMs the following parameters were varied: Young's modulus (E), Poisson's ratio (nu) in range 0.49-0.4999, catheter position (translation of 0.8 mm), and cap thickness (t) in range 50-350 microm. Hereby the resulting peak radial strain (PRS) was determined and visualized. RESULTS: Measured static E for phantom was 4.2 kPa for plaque and 16.8 kPa for wall.Variation of E-wall in range 8.4-33.2 kPa and/or E-plaque in range 2.1-8.4 kPa using the phantom FEM, gave a PRS variation of 1.6%, i.e. from 1.7% up to almost 3.3%; for variation in nu this was only 0.07%, i.e. from 2.37% up to 2.44%. Variation of E-lipid in range 6.25-400 kPa and E-cap in range 700-2300 kPa using the artery FEM, gave a PRS variation of 3.1%, i.e. from 0.6% up to 3.7%. The PRS was higher for lower E-lipid and E-cap; it was located at a shoulder of the lipid pool. Variation of nu gave only a variation of 0.17%. Variation of t and E-cap resulted in a PRS variation of 1.4%, i.e. from 0.3% up to 1.7%; thinner and weaker caps gave higher PRS. Catheter position variation changed radial strain value. CONCLUSIONS: Measured IVUS elastograms of vulnerable plaques depend highly upon the Young's modulus of lipid and cap, but not upon the Poisson's ratio. Different catheter positions result in different IVUS elastograms, but the diagnostically important high strain regions at the lipid shoulders are often still detectable. PRS increases when cap weakens or cap thickness decreases.     

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.     

Quo vadis elasticity imaging?

In the past decade, an important field that has emerged as complementary to ultrasonic imaging is that of elasticity imaging. The term encompasses a variety of techniques that can depict a mechanical response or property of tissues. In ultrasound, its premise is built on two important facts: (a) that significant differences between mechanical properties of several tissue components exist and (b) that the information contained in the coherent scattering, or speckle, is sufficient to depict these differences following an external or internal mechanical stimulus. Parameters, such as velocity of vibration, displacement, strain, strain rate, velocity of wave propagation and elastic modulus, have all been demonstrated feasible in their estimation and have resulted in the accurate depiction of stiffer tissue masses, such as tumors, high-intensity focused ultrasound (HIFU) lesions and atherosclerotic plaques. More recently, through the development of ultrafast algorithms tailored to suitable hardware as well as the familiarity of the physician with the sensitivity of the methods used, one elasticity imaging technique in particular, elastography, has been shown applicable in a typical clinical ultrasound setting. In other words, elastograms can currently be obtained at quasi real-time (approximately at a frame rate of 8 frames/s) and with the use of a hand-held transducer (as opposed to the previously used frame-suspended setup) during and simultaneously with an ultrasound exam of, e.g., the breast or the prostate. The higher frame rate available with certain clinical ultrasound scanners has also resulted in the successful application of elasticity imaging techniques on the myocardium and monitoring its deformation over several cardiac cycles for the detection of ischemic regions. As a result, elasticity imaging with its ever increasing number of applications and demonstrated applicability in a typical, clinical ultrasound setting promises to make an important contribution to the ultrasound practice as we know it.     

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.     

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.     

Angle matching in intravascular elastography

Intravascular elastography is a new technique to obtain mechanical properties of the vessel wall and plaque. Mechanical information of vascular tissue is important for characterisation of different plaque components, detection of plaque vulnerability and thus choosing the proper interventional technique. The feasibility of the technique is investigated using phantoms and diseased human arteries. These studies demonstrated that elastography reveals information that is unavailable or inconclusive from the echogram alone. The technique is based on the principle that tissue strain is directly related to its mechanical properties. In intravascular elastography, the tissue is compressed using different intravascular pressures. The strain is determined using cross-correlation techniques of the radio frequency (r.f.) signals. Reliable strain estimates are only obtained when signals of corresponding tissue are correlated. Owing to catheter motion, off-centre position and non-uniform rotation of the intravascular transducer, the r.f. traces at low and at high pressure may be misaligned. Four algorithms are tested to track the corresponding ultrasound signals. Three methods (l1norm, l2norm and cross-correlation) are applied on the r.f. signal and one (l1norm) on the envelope (speckle tracking). Simulations are performed to obtain a data set with a priori knowledge of the scattering particles positions in the tissue at high and low pressure. Different positions of the catheter in the lumen, compression levels of the material and signal-to-noise ratios (SNRs) are investigated. Finally, these findings are corroborated with a phantom experiment in a water tank. From the simulations, it can be concluded that the speckle tracking algorithm has the best performance, under all circumstances. The performance decreases with larger eccentricity of the catheter and larger compression of the material. The SNR is only of minor influence. The speckle tracking algorithm has also the best performance in the phantom experiment. The performance of the speckle tracking algorithm is better than the three r.f.-based algorithms. For intravascular elastography, implementation of this method may improve the quality of the elastogram.     

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…     

Visualization and Characterization of Atherosclerotic Plaques by Micro-MRI at 4.7 T In Vivo and 11.7 T Ex Vivo

The aim of this study was to evaluate the capability of using micro-magnetic resonance imaging (MRI) to visualize and characterize atherosclerotic plaques of mouse models. Twenty five apolipoprotein E-knockout mice were fed atherogenic diet, which enabled creation of aortic atherosclerotic plaques. Aortic plaques were examined in vivo by 4.7 T MRI and then characterized ex vivo by 11.7 T three-dimensional MRI. MR images were correlated with subsequent histological confirmation. In vivo 4.7-T MRI demonstrated unevenly thickened aortic walls due to formation of atherosclerotic plaques. Ex vivo 11.7-T MRI enabled not only to acquire full volume-rendered images of the entire vessels but also to characterize plaque components (such as lipid cores and fibrous caps) at any level and any projection, which were confirmed by histological correlation. Micro-MRI provides an excellent imaging tool for basic science to investigate atherosclerosis in small animal models, which may become a supplement to histopathology of atherosclerotic cardiovascular disease.     

MRI-based biomechanical imaging: initial study on early plaque progression and vessel remodeling

The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomechanical imaging technique to address biomechanical pathways of atherosclerotic progression and regression in vivo using a 3D fluid-structure interaction (FSI) model. Initial in vivo study was carried out in an early plaque model in pigs that underwent balloon-overstretch injury to the left carotid arteries. Consecutive MRI scans were performed while the pigs were maintained on high cholesterol (progression) or normal chow (regression), with an injection of a plaque-targeted contrast agent, Gadofluorine M. At the end of study, the specimens of carotid arterial segments were dissected and underwent dedicated mechanical testing to determine their material properties. 3D FSI computational model was applied to calculate structure stress and strain distribution. The plaque structure resembles early plaque with thickened intima. Lower maximal flow shear stress correlates with the growth of plaque volume during progression, but not during regression. In contrast, maximal principle structure stress/stain (stress-P1 and strain-P1) were shown to correlate strongly with the change in the plaque dimension during regression, but moderately during progression. This MRI-based biomechanical imaging method may allow for noninvasive dynamic assessment of local hemodynamic forces on the development of atherosclerotic plaques in vivo.     

Noninvasive detection of intimal xanthoma using combined ultrasound, strain rate and photoacoustic imaging

Background and motivation

The structure, composition and mechanics of carotid artery are good indicators of early progressive atherosclerotic lesions. The combination of three imaging modalities (ultrasound, strain rate and photoacoustic imaging) which could provide corroborative information about the named arterial properties could enhance the characterization of intimal xanthoma.

Methods

The experiments were performed using a New Zealand white rabbit model of atherosclerosis. The aorta excised from an atherosclerotic rabbit was scanned ex vivo using the three imaging techniques: (1) ultrasound imaging of the longitudinal section: standard ultrasound B-mode (74 Hz frame rate); (2) strain rate imaging: the artery was flushed with blood and a 1.5 Hz physiologic pulsation was induced, while the ultrasound data were recorded at higher frame rate (296 Hz); (3) photoacoustic imaging: the artery was irradiated with nanosecond pulsed laser light of low fluence in the 1210-1230 nm wavelength range and the photoacoustic data was recorded at 10 Hz frame rate. Post processing algorithms based on cross-correlation and optical absorption variation were implemented to derive strain rate and spectroscopic photoacoustic images, respectively.

Results

Based on the spatio-temporal variation in displacement of different regions within the arterial wall, strain rate imaging reveals differences in tissue mechanical properties. Additionally, spectroscopic photoacoustic imaging can spatially resolve the optical absorption properties of arterial tissue and identify the location of lipid pools.

Conclusions

The study demonstrates that ultrasound, strain rate and photoacoustic imaging can be used to simultaneously evaluate the structure, the mechanics and the composition of atherosclerotic lesions to improve the assessment of plaque vulnerability.     

Intravascular photoacoustic imaging of human coronary atherosclerosis

We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. The data was obtained from two fresh human coronary arteries ex vivo, showing different stages of disease. A 1.25?mm diameter intravascular imaging catheter was built, comprising an angle-polished optical fiber adjacent to a 30?MHz ultrasound transducer. Specific photoacoustic imaging of lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230?nm. Simultaneous imaging with intravascular ultrasound was performed.     

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.     

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.     

激光诱导荧光光谱识别动脉粥样硬化斑块的研究

采用氩离子激光为激发光源,分别研究了离体正常动脉壁、动脉粥样硬化斑块和血液等的激光诱导荧光光谱.结果表明,正常动脉壁样品组的荧光光谱强度最大值明显高于动脉粥样硬化斑块样品组;斑块的荧光光谱在516 nm处存在一个小波谷,而正常动脉组织的荧光光谱则无此波谷;斑块组织在598 nm处与578 nm处的荧光强度比值R(I₅₉₈ nm/I₅₇₈ nm)远低于正常动脉壁的比值;血红蛋白含量是引起粥样斑块与正常动脉壁的R(I₅₉₈ nm/I₅₇₈ nm)值不同的主要原因.     

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.     

Targeting and deep-penetrating delivery strategy for stented coronary artery by magnetic guidance and ultrasound stimulation

Stent placement is an effective treatment for atherosclerosis, but is suffered from in-stent restenosis (ISR) caused by stent mechanical damage. Conventional ISR treatment such as drug-eluting stents (DES) is challenged by the low therapeutic efficacy and severe complications, unchangeable drug dosage for individuals, and limited drug penetration in the vascular tissue. We hypothesize that magnetic targeting and deep-penetrating delivery strategy by magnetic guidance and ultrasound stimulation might be an effective approach for ISR treatment. In the present study, antiproliferative drug (paclitaxel, PTX) loaded poly (lactide-co-glycolide) (PLGA) nanoparticles (PLGA-PTX) were embedded within the shells of the magnetic nanoparticle coated microbubbles (MMB-PLGA-PTX). Once being targeted to the stent under a magnetic field, a low intensity focused ultrasound (LIFU) is applied to activate stable microbubble oscillations, thereby triggering the release of PLGA-PTX. The generated mechanical force and microstreaming facilitate the penetration of released PLGA-PTX into the thickened vascular tissue and enhance their internalization by smooth muscle cells (SMCs), thereby reducing the clearance by blood flow. In an ex vivo experiment, magnetic targeting improved the accumulation amount of MMB-PLGA-PTX by 10 folds, while the LIFU facilitated the penetration of released PLGA-PTX into the tunica media region of the porcine coronary artery, resulting in prolonged retention time at the stented vascular tissue. With the combination effects, this strategy holds great promise in the precision delivery of antiproliferative drugs to the stented vascular tissue for ISR treatment.     

Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis

Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation time constant varied significantly for vulnerable aortic plaques (tau=40 ms) versus stable plaques (tau=400 ms) and normal aorta (tau=500 ms) . These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations.     

A 2D strain estimator with numerical optimization method for soft-tissue elastography

Elastography is a bioelasticity-based imaging modality which has been proved to be a potential evaluation tool to detect the tissue abnormalities. Conventional method for elastography is to estimate the displacement based on cross-correlation technique firstly, then strain profile is calculated as the gradient of the displacement. The main problem of this method arises from the fact that the cross-correlation between pre- and post-compression signals will be decreased because of the signal’s compression-to-deformation. It may constrain the estimation of the displacement. Numerical optimization, as an efficient tool to estimate the non-rigid deformation in image registration, has its potential to achieve the elastogram. This paper incorporates the idea of image registration into elastography and proposes a radio frenquency (RF) signal registration strain estimator based on the minimization of a cost function using numerical optimization method with Powell algorithm (NOMPA). To evaluate the proposed scheme, the simulation data with a hard inclusion embedded in the homogeneous background is produced for analysis. NOMPA can obtain the displacement profiles and strain profiles simultaneously. When compared with the cross-correlation based method, NOMPA presents better signal-to-noise ratio (SNR, 32.6 ± 1.5 dB vs. 23.8 ± 1.1 dB) and contrast-to-noise ratio (CNR, 28.8 ± 1.8 dB vs. 21.7 ± 0.9 dB) in axial normal strain estimation. The in vitro experiment of porcine liver with ethanol-induced lesion is also studied. The statistic results of SNR and CNR indicate that strain profiles by NOMPA performs better anti-noise and target detectability than that by cross-correlation based method. Though NOMPA carry a heavier computational burden than cross-correlation based method, it may be an useful method to obtain 2D strains in elastography.