3D ultrasound analysis of carotid plaque volume and surface morphology

Morphological characterization of carotid plaques has been used for risk stratification and evaluation of response to therapy, evaluation of new risk factors, genetic research, and for quantifying effects of new anti-atherosclerotic therapies. We developed a 3D US system that allows detailed studies of carotid plaques in 3D. Our software includes 3D reconstruction, viewing, manual and semi-automated segmentation of carotid plaques, and surface morphology analysis to be used for quantitative tracking of plaque changes. We evaluated our plaque quantification software by examining plaque volume measurement accuracy, variability, and plaque surface morphology. We used vascular test phantoms to study segmentation accuracy, and used 48 3D US carotid plaques of patients ranging in size from 13.2 mm(3) to 544.0 mm(3) to study plaque volume measurement variability. We compared results from the semi-automated plaque measurements to the results obtained from manual measurements, which were used as the "gold" standard. We developed a surface plaque morphology quantification technique based on the segmented plaque surface curvature and used it to analyze plaques. Accuracy of plaque volume measurements for the simulated plaques ranged from 4.2% to 1.5% for volumes ranging from 68.5 mm(3) to 286 mm(3). The variability study showed that coefficients of variation in the measurement of plaque volume decreased with increasing plaque size for both inter- (90.8-3.9%) and intra-observer (70.2-3.1%) measurements over the plaque sizes measured. Surface morphology analysis showed that 1 mm ulceration could be quantified and monitored for changes over time. The automated plaque quantification approach showed a little higher intra-observer variability than the manual technique, and its performance was better for segmenting the wall than the lumen. Our results indicate that our approach is sensitive tool and can be used in studies of plaque progression and regression as it relates to atherosclerosis treatment effects and can be used effectively in longitudinal studies for direct measurement carotid plaque volume.     

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.     

Assessment of the reliability of the determination of carotid artery lumen sizes by quantitative image processing of magnetic resonance angiograms and images

In order to use MR imaging to assess progression or regression of atherosclerosis, one must have an idea of the reproducibility of the imaging and image processing techniques. The ability of dark-blood MRI and semiautomated image processing to reproducibility measure the inner boundary of the carotid arteries was evaluated and compared with results obtained using bright-blood MRA. MRI and MRA images were obtained for two normal and two diseased volunteers six times each over a short period of time (6 months). The carotid bifurcation was used to align slices from different imaging sessions. The area for each vessel (right and left common, internal and external carotid artery) was determined for the six imaging sessions. The standard deviations of each lumen area normalized to the average area were computed for each vessel segment for each volunteer. For the common, internal, and external carotids, the averaged normalized standard deviations for MRI were 8, 12, and 17% and for MRA were 6, 8, and 13%. Lumen sizes obtained by MRI and MRA were found to be not statistically different. Eccentric plaques not seen on MRA were visualized by MRI. In conclusion, dark-blood MRI with semiautomated image processing yields reliable lumen areas that are in agreement with those obtained by MRA.     

Comparison of carotid vessel wall area measurements using three different contrast-weighted black blood MR imaging techniques

Measuring carotid artery plaque burden from MRI is a reliable method for monitoring regression and progression of atherosclerosis. However, to measure all available images would be very time consuming, and in practice the image quality (IQ) of these images may be inconsistent, which can directly impact the quality of measurement. It is hypothesized that if IQ is comparable among different contrast weighted images, then carotid artery area measurements obtained from different contrast images of the same location will produce identical results. To test this, T1, proton density and T2 weighted images were acquired from ten patients (51 +/- 7 years old). Carotid lumen and vessel wall area was measured using a custom designed software program. The results showed strong agreement evidenced with only small differences on both lumen (mean: 40.5 mm(2)) and wall (mean: 52.6 mm(2)) area measurement among different weighted images. The maximum absolute mean differences are less than 2.7 mm(2) and 4.4 mm(2), and 90(th) percentile of the absolute differences are 5.6 mm(2) and 8.2 mm(2) respectively. In conclusion, different contrast weighted images with high and comparable IQ will yield similar results in lumen and vessel wall area measurement. At each matched location, it is recommended that the image with the highest IQ be used for area measurement.     

Quantitation of atherosclerosis by magnetic resonance imaging and 3-D morphology operators

The objective was to ascertain whether MRI and image processing can be used to quantify atherosclerosis by measuring wall thickness in rabbit aorta. The abdominal aortas of 2 healthy and 5 atherosclerotic rabbits were examined with a gradient-echo inflow angiography sequence (2DI) and a proton density weighted turbo-spin-echo sequence (PDW). Using thresholding by four observers and 3D morphology operators, segmentation of the artery and vein lumina was performed from the 2DI sequence, and of surrounding fat and muscle from the PDW sequence. Remaining voxels adjacent to the aortic lumen were classified as vessel wall. By measuring the vessel wall volume and the lumen volume, the wall percentage was calculated. The values were significantly higher for the diseased animals than for unaffected individuals (p < 0.01). It is concluded that aortic wall thickening in atherosclerotic rabbits can be measured quantitatively by using MRI combined with 3D morphology image processing operators.     

Lattice Boltzmann method simulating hemodynamics in the three-dimensional stenosed and recanalized human carotid bifurcations

By using the lattice Boltzmann method(LBM)pulsatile blood flows were simulated in three-dimensional moderate stenosed and recanalized carotid bifurcations to understand local hemodynamics and its relevance in arterial atherosclerosis formation and progression.The helical flow patterns,secondary flow and wall dynamical pressure spatiotemporal distributions were investigated,which leads to the disturbed shear forces in the carotid artery bifurcations.The wall shear stress distributions indicated by time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI),and the relative residence time(RRT)in a cardiac cycle revealed the regions where atherosclerotic plaques are prone to form,extend or rupture.This study also illustrates the point that locally disturbed flow may be considered as an indicator for early atherosclerosis diagnosis.Additionally the present work demonstrates the robust and highly efficient advantages of the LBM for the hemodynamics study of the human blood vessel system.     

Novel methodology for 3D reconstruction of carotid arteries and plaque characterization based upon magnetic resonance imaging carotid angiography data

In this study, we present a novel methodology that allows reliable segmentation of the magnetic resonance images (MRIs) for accurate fully automated three-dimensional (3D) reconstruction of the carotid arteries and semiautomated characterization of plaque type. Our approach uses active contours to detect the luminal borders in the time-of-flight images and the outer vessel wall borders in the T(1)-weighted images. The methodology incorporates the connecting components theory for the automated identification of the bifurcation region and a knowledge-based algorithm for the accurate characterization of the plaque components. The proposed segmentation method was validated in randomly selected MRI frames analyzed offline by two expert observers. The interobserver variability of the method for the lumen and outer vessel wall was -1.60%±6.70% and 0.56%±6.28%, respectively, while the Williams Index for all metrics was close to unity. The methodology implemented to identify the composition of the plaque was also validated in 591 images acquired from 24 patients. The obtained Cohen's k was 0.68 (0.60-0.76) for lipid plaques, while the time needed to process an MRI sequence for 3D reconstruction was only 30 s. The obtained results indicate that the proposed methodology allows reliable and automated detection of the luminal and vessel wall borders and fast and accurate characterization of plaque type in carotid MRI sequences. These features render the currently presented methodology a useful tool in the clinical and research arena.     

Closed contour edge detection of blood vessel lumen and outer wall boundaries in black-blood MR images

Quantitative measurements of the blood vessel wall area may provide useful information of atherosclerotic plaque burden, progression and/or regression. Magnetic resonance imaging is a promising technique for identifying both luminal and outer wall boundaries of the human blood vessels. Currently these boundaries are primarily defined manually, a process viewed as labor intensive and subject to significant operator bias. Fully automated post-processing techniques used for identifying the lumen and wall boundaries, on the other hand, are also problematic due to the complexity of signal features in the vicinity of the blood vessels. The goals of this study were to develop a robust, automated closed contour edge detection algorithm, apply this algorithm to high resolution human carotid artery images, and assess its accuracy, and reproducibility. Our algorithm has proven to be sensitive to various contrast situations and is reasonably accurate and highly reproducible.     

Discrimination of components in atherosclerotic plaques from human carotid endarterectomy specimens by magnetic resonance imaging ex vivo

Specific MRI techniques have been used to determine the dimensional and compositional properties of atherosclerotic lesions in carotid endarterectomy tissues. A quantitative comparison of areas of specific features in typical tissue segments was performed using MR images and histologic images. The mean difference for the measurements by the two methods was 4.5% for the total vessel, 5.3% for the internal carotid artery lumen, and 5.0% for the external carotid lumen. For other less abundant components, the mean difference was 14.2%. For direct characterization, individual tissue components were isolated by microdissection and their T1 and T2 relaxation times measured. Highly calcified areas typically had rather short T1 (452-837 ms) and short T2 (10.4-18.4 ms). In contrast, regions enriched in lipid had much longer T1 (1,380-1,480 ms) and longer T2 (35.3-49.0 ms). Other components such as thrombus had intermediate T1 (1,180 ms) and short T2 (15.4 ms). T2 parametric imaging was used as a complementary approach for segmentation and quantitation of tissue components. In fresh tissue, several different components exhibited different T2 ranges: calcified/solid lipid (13-18 ms). cellular/ECM (9-30 ms), fluid lipid (35-40 ms): fibrous (50-60 ms). These results demonstrate the utility of MRI for identifying and quantifying specific components of atherosclerotic plaque ex vivo, and suggest its value for these measurements in vivo as well.     

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.     

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.     

Computational fluid dynamics tools can be used to predict the progression of coronary artery disease

Atherosclerosis is focal and individual plaques evolve in an independent manner. The endothelium regulates arterial behavior by responding to its local shear stress. In vitro studies indicate that low endothelial shear stress (ESS) upregulates the genetic and molecular responses leading to the initiation and progression of atherosclerosis and promotes inflammation and formation of other features characteristic of vulnerable plaque. Physiologic ESS is vasculoprotective and fosters quiescence of the endothelium and vascular wall. High ESS promotes platelet aggregation. ESS and vascular wall morphology along the course of human coronary arteries can now be characterized in vivo, and may predict the focal areas in which atherosclerosis progression occurs. Rapidly evolving methodologies are able to characterize the arterial wall and the local hemodynamic factors likely responsible for progression of coronary disease in man. These new diagnostic modalities allow for identification of plaque progression. Accurate identification of arterial segments at high-risk for progression may permit pre-emptive intervention strategies to avoid adverse coronary events.     

3D high-resolution contrast enhanced MRI of carotid atheroma — a technical update

Objective

Development of a fast 3D high-resolution magnetic resonance imaging (MRI) protocol for improved carotid artery plaque imaging.

Methods

Two patients with carotid atherosclerosis disease underwent 3D high-resolution MRI which included time-of-flight and T₁-weighted variable flip angle, fast-spin-echo (FSE) imaging, pre- and post-intravenous gadolinium-based contrast agent administration.

Results

Good quality images with intrinsic blood suppression were obtained pre- and post-contrast administration using a 3D FSE sequence. The plaque burden, lipid core volume, hemorrhage volume and fibrous cap thickness were well determined.

Conclusions

3D high-resolution MR imaging of carotid plaque using TOF and 3D FSE can achieve high isotropic resolution, large coverage, and excellent image quality within a short acquisition time.     

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.     

Computerized quantification of carotid artery stenosis using MRA axial images

Currently, the North American symptomatic carotid endarterectomy trial, European carotid surgery trial, and common carotid method are used to measure the carotid stenosis for determining candidates for carotid endarterectomy using the projection angiography from different modalities such as digital subtraction angiography, rotational angiography, computed tomography angiography and magnetic resonance angiography. A new computerized carotid stenosis measuring system was developed using MR angiography axial image to overcome the drawbacks of conventional carotid stenosis measuring methods, to reduce the variability of inter-observer and intra-observer. The gray-level thresholding is one of the most popular and efficient methods for image segmentation. We segmented the carotid artery and lumen from three-dimensional time-of-flight MRA axial images using gray-level thresholding technique. Using the measured intima-media thickness value of common carotid artery for each case, we separated carotid artery wall from the segmented carotid artery region. After that, the regions of segmented carotid without artery wall were divided into region of blood flow and plaque. The calculation of carotid stenosis degree was performed as follows: carotid stenosis grading = (area measure of plaque/area measure of blood flow region and plaque) * 100%. No previous study has developed the carotid stenosis measuring method using MRA axial image. The new computerized stenosis measuring system has advantage over conventional caliper measuring methods; it will not only greatly increase the speed of stenosis measuring but also reduce the variability between readers. It should also reduce the variability between different institutions.     

Arterial culprit plaque characteristics revealed by magnetic resonance Vessel Wall imaging in patients with single or multiple infarcts

PurposeTo investigate characteristics of intra- and extracranial arterial culprit plaques between patients with single infarct and multiple-infarcts by a head-neck combined high resolution magnetic resonance vessel wall imaging (HR-MRVWI).Materials and methodsForty-three patients with recent ischemic stroke due to large artery atherosclerosis were enrolled. The head-neck combined HR-MRVWI was performed in all patients both pre- and post-contrast administration. Based on diffusion weighted imaging findings, patients were divided into single-infarction and multiple-infarction groups. For patients with anterior circulation ischemic stroke, they were also divided into perforating artery infarction (PAI) and non-PAI groups. Patient demographics, number and location of culprit plaques, artery stenosis percentage, intraplaque hemorrhage, and plaque enhancement were evaluated and compared between single-infarction and multiple-infarction groups, as well as between PAI and non-PAI groups.ResultsA total of 83 culprit plaques were identified. The artery stenosis degree was more severe and plaque enhancement more prominent in multiple-infarction group than in single-infarction group. Patients with multiple infarcts also had more culprit plaques per patient than those with single infarct, which contributed to the occurrence of multiple infarcts. For comparison of PAI and non-PAI groups, a higher artery stenosis percentage was observed in non-PAI group, and patients with non-PAI had more culprit plaques per patient, which contributed to a variety of infarct manifestations.ConclusionA higher stenosis grade and higher number of culprit plaques seem to be associated with a higher number of cerebral infarcts in patients with large artery atherosclerosis.     

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.     

A fast screening protocol for carotid plaques imaging using 3D multi-contrast MRI without contrast agent

PurposeTo implement a fast (~ 15 min) MRI protocol for carotid plaque screening using 3D multi-contrast MRI sequences without contrast agent on a 3 Tesla MRI scanner.Materials and methods7 healthy volunteers and 25 patients with clinically confirmed transient ischemic attack or suspected cerebrovascular ischemia were included in this study. The proposed protocol, including 3D T1-weighted and T2-weighted SPACE (variable-flip-angle 3D turbo spin echo), and T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) was performed first and was followed by 2D T1-weighted and T2-weighted turbo spin echo, and post-contrast T1-weighted SPACE sequences. Image quality, number of plaques, and vessel wall thicknesses measured at the intersection of the plaques were evaluated and compared between sequences.ResultsAverage examination time of the proposed protocol was 14.6 min. The average image quality scores of 3D T1-weighted, T2-weighted SPACE, and T1-weighted magnetization prepared rapid acquisition gradient echo were 3.69, 3.75, and 3.48, respectively. There was no significant difference in detecting the number of plaques and vulnerable plaques using pre-contrast 3D images with or without post-contrast T1-weighted SPACE. The 3D SPACE and 2D turbo spin echo sequences had excellent agreement (R = 0.96 for T1-weighted and 0.98 for T2-weighted, p < 0.001) regarding vessel wall thickness measurements.ConclusionThe proposed protocol demonstrated the feasibility of attaining carotid plaque screening within a 15-minute scan, which provided sufficient anatomical coverage and critical diagnostic information. This protocol offers the potential for rapid and reliable screening for carotid plaques without contrast agent.     

Co-registration of the distribution of wall shear stress and 140 complex plaques of the aorta

Previous studies provide evidence that atherosclerosis develops in vascular regions exposed to low wall shear stress (WSS) and high oscillatory shear index (OSI). 4D flow MRI was analyzed in 70 stroke patients with complex plaques (≥ 4 mm thickness, ulcerated or superimposed thrombi) and in 12 young healthy volunteers. The segmental distribution of peak systolic WSS_systole and OSI was quantified in analysis planes positioned directly at the location of 140 complex plaques found in the 70 patients. In addition, WSS_systole and OSI were evaluated in 8 standard analysis planes distributed along the aorta. Complex plaques were predominantly found at the inner curvature of the aortic arch and of the descending aorta. High OSI was co-located with the segments mostly affected by complex plaque while WSS_systole demonstrated a homogenous distribution. In standard analysis planes, patients demonstrated significantly (p < 0.01) altered distribution of wall parameters compared to volunteers (reduced WSS_systole in 91% of aortic wall segments, increased OSI in 48% of segments). OSI distribution was asymmetric with higher values at the inner curvature of the aorta. While WSS and OSI showed expected changes in patients compared to healthy controls, their distribution pattern at complex plaques indicated a more complex and heterogeneous relationship than previously anticipated.