Carotid Plaque Imaging Research Articles

3.0 T Plaque Imaging

The aim of this article is to evaluate 3.0 T magnetic resonance imaging for characterization of vessel morphology and plaque composition. Emphasis is placed on early and moderate stages of carotid atherosclerosis, where increases in signal-to-noise (SNR) and contrast-to-noise (CNR) ratios compared with 1.5 T are sought. Comparison of in vivo 3.0 T imaging to histopathology is performed for validation. Parallel acceleration methods applied with an 8-channel carotid array are investigated as well as higher field ex vivo imaging to explore even further gains. The overall endeavor is to improve prospective assessment of atherosclerosis stage and stability for reduction of atherothrombotic event risk. A total of 10 male and female subjects ranging in age from 22 to 72 years (5 healthy and 5 with cardiovascular disease) participated. Custom-built array coils were used with endogenous and exogenous multicontrast bright and black-blood protocols for 3.0 T carotid imaging. Comparisons were performed to 1.5 T, and ex vivo plaque was stained with hematoxylin and eosin for histology. Imaging (9.4 T) was also performed on intact specimens. The factor of 2 gain in signal-to-noise SNR is realized compared with 1.5 T along with improved wall-lumen and plaque component CNR. Post-contrast black-blood imaging within 5-10 minutes of gadolinium injection is optimal for detection of the necrotic lipid component. In a preliminary 18-month follow-up study, this method provided measurement of a 50% reduction in lipid content with minimal change in plaque size in a subject receiving aggressive statin therapy. Parallel imaging applied with signal averaging further improves 3.0 T black-blood vessel wall imaging. The use of 3.0 T for carotid plaque imaging has demonstrated increases in SNR and CNR compared with 1.5 T. Quantitative prospective studies of moderate and early plaques are feasible at 3.0 T. Continued improvements in coil arrays, 3-dimensional pulse sequences, and the use of novel molecular imaging agents implemented at high field will further improve magnetic resonance plaque characterization.

Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging–based finite element analysis

Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses. Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted. There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition. Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging-based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.

Texture Analysis of Ultrasonic Images of Symptomatic Carotid Plaques can Identify Those Plaques Associated with Ipsilateral Embolic Brain Infarction

The aim of our study was to determine the association between objective, computerised texture analysis of carotid plaque ultrasonic images and embolic CT-brain infarction in patients presenting with hemispheric neurological symptoms. Cross-sectional study in patients with 50%-99% (ECST) carotid stenosis. Carotid plaque ultrasonic images (n=54, 26 with TIAs and 28 with stroke) obtained during carotid ultrasound were normalised and standardised for resolution and subsequently assessed visually for the presence of discrete echogenic or juxtaluminal echolucent components and overall echogenicity (plaque type). Using computer software, 51 histogram/textural features of the plaque outlines were calculated. Factor analysis was subsequently applied to eliminate redundant variables. Small cortical, large cortical and discrete subcortical infarcts on CT-brain scan were considered as being embolic. Twenty-five cases (46%) had embolic infarcts. On logistic regression, grey-scale median (GSM), a measure of echolucency, spatial grey level dependence matrices (SGLDM) correlation and SGLDM information measure of correlation-1, measures of homogeneity were significant (p<0.05), but not grey level runlength statistics (RUNL) Run Percentage (RP), stenosis severity, type of symptoms or echolucent juxtaluminal components. Using ROC curves methodology, SGLDM information measure of correlation-1 improved the value of GSM in distinguishing embolic from non-embolic CT-brain infarction. Computerised texture analysis of ultrasonic images of symptomatic carotid plaques can identify those that are associated with brain infarction, improving the results achieved by GSM alone. This methodology could be applied to prospective natural history studies of symptomatic patients not operated on or randomised trials of patients undergoing carotid angioplasty and stenting in order to identify high-risk subgroups for cerebral infarction.

Inflammatory Biomarkers in Acute Coronary Syndromes

The inflammatory etiology of atherosclerosis has prompted a search for biomarkers of inflammation that predict risk for coronary artery disease and its sequelae. Within the acute coronary syndromes (ACS), inflammatory biomarkers may provide independent information regarding pathophysiology, prognosis, and optimal therapeutic strategies. On the basis of the hypothesis that different pathophysiological processes provide nonoverlapping information regarding risk stratification and disease management, this review series addresses biomarkers for each step in the inflammatory process that leads to ACS. Part I reviewed cytokines; this part reviews acute-phase reactants and biomarkers of endothelial cell activation; subsequent parts will address biomarkers of oxidative stress, angiogenesis, extracellular matrix degradation, and platelet activation. In the acute-phase response, cytokines drive production of acute-phase reactants, defined by >25% change in circulating concentration during an inflammatory response. These markers may also remain elevated chronically because of continuing inflammatory stimuli (Table). View this table: Inflammatory Biomarkers in ACS ### C-Reactive Protein C-reactive protein (CRP) is a pentraxin acute-phase protein, members of which are evolutionarily conserved in most vertebrates.1 Hepatocytes and possibly smooth muscle cells and macrophages transcriptionally activate production of CRP in response to inflammatory cytokines, including interleukin-1 and interleukin-6.2 CRP is a robust clinical marker because of its stability, reproducible results, and ease of assay. Although it was originally proposed as a nonspecific marker of inflammation, several reports suggest that CRP may play a direct pathophysiological role in the development and progression of atherosclerosis. Proposed mechanisms include induction of endothelial dysfunction,3 promotion of foam cell formation,4 inhibition of endothelial progenitor cell survival and differentiation,5 and activation of complement in atherosclerotic plaque intima6 and ischemic myocardium.7 Patients with ACS have elevations in CRP in association with their presenting symptoms. There appears to be a bimodal CRP response among patients with ACS. In some patients, CRP may remain elevated for …

Effect of zooming on texture features of ultrasonic images

BackgroundUnstable carotid plaques on subjective, visual, assessment using B-mode ultrasound scanning appear as echolucent and heterogeneous. Although previous studies on computer assisted plaque characterisation have standardised B-mode images for brightness, improving the objective assessment of echolucency, little progress has been made towards standardisation of texture analysis methods, which assess plaque heterogeneity. The aim of the present study was to investigate the influence of image zooming during ultrasound scanning on textural features and to test whether or not resolution standardisation decreases the variability introduced.MethodsEighteen still B-mode images of carotid plaques were zoomed during carotid scanning (zoom factor 1.3) and both images were transferred to a PC and normalised. Using bilinear and bicubic interpolation, the original images were interpolated in a process of simulating off-line zoom using the same interpolation factor. With the aid of the colour-coded image, carotid plaques of the original, zoomed and two resampled images for each case were outlined and histogram, first order and second order statistics were subsequently calculated.ResultsMost second order statistics (21/25, 84%) were significantly (p < 0.05) sensitive to image zooming during scanning, in contrast to histogram and first order statistics (4/25, 16%, p < 0.001, Fisher's exact test). Median (interquartile range) change of those features sensitive to zooming was 18.14% (4.94–28.43). Image interpolation restored these changes, the bicubic interpolation being superior compared to bilinear interpolation (p = 0.036).ConclusionTexture analysis of ultrasonic plaques should be performed under standardised resolution settings; otherwise a resolution normalisation algorithm should be applied.

Utility of MRA and CTA in the Evaluation of Carotid Occlusive Disease

Cervical carotid artery atherosclerotic disease is an important cause of thromboembolic stroke. Noninvasive imaging techniques have become preferred in initial diagnostic workup. We review the current approach to carotid imaging, and the clinical utility and limitations of carotid computed tomography angiography (CTA) and magnetic resonance angiography (MRA). Future directions of these modalities, including carotid plaque imaging, are also discussed.

A Critical Appraisal of the Performance, Reporting, and Interpretation of Studies Comparing Carotid Plaque Imaging With Histology

Carotid plaque instability is an important determinant of stroke risk. There are now a number of different imaging techniques that provide information on carotid plaque morphology. However, it is unclear how they compare with one another or whether they can reliably assess plaque instability. Studies comparing imaging with pathology have shown highly variable results, even for similar imaging techniques. This may be because of variable pathology techniques rather than differences in imaging. We performed a systematic review of studies that compared carotid imaging with histology of the excised plaque published between January 1995 and September 2004. We assessed the quality and comparability of these studies. In particular, we determined which histology methods were used and whether observer reproducibility of the histology assessment was reported. Among 73 eligible studies, histological methods were poorly reported and highly variable; 23% reported reproducibility data for imaging and only 12% reported reproducibility data for histology. Of 29 studies that reported quantitative results of blinded comparisons, there were methodological deficiencies and the results were highly variable. No study considered the extent to which the lack of reproducibility influenced the imaging-pathological correlations reported. Pathological correlation in studies of carotid plaque imaging cannot be reliably interpreted or compared because of incomparable and poorly reported histology methods. We make recommendations for the performance, reporting, and interpretation of imaging-pathological correlation studies and highlight the need for consensus guidelines.

Reproducibility of Histological Assessment of Carotid Plaque: Implications for Studies of Carotid Imaging

Background: Thromboembolism from carotid plaque is an important cause of stroke. Identification of unstable plaque would therefore be clinically useful. Unfortunately, studies of carotid plaque imaging have shown poor agreement with histology. However, this may be due to inconsistent methods and the variability of assessments of carotid plaque histology, rather than inadequate imaging. Methods: We assessed the reproducibility of histological assessment in 60 plaques, and section-to-section variability along the length of 26 plaques. Results: Kappa values ranged from 0.35 to 0.89 and from 0.44 to 0.68, respectively, for intra- and inter-observer reproducibility. There was considerable section-to-section variability within plaques. Conclusions: The accuracy of imaging of carotid plaque morphology will be underestimated unless variability in the histology assessment is taken into account.

High-Resolusion Magnetic Resonance Imaging of Carotid Atherosclerotic Plaque

A thromboembolic stroke is believed to be precipitated by a rupture of vulnerable atheromatous plaques. Until recently the assessment of a further risk of stroke in high-risk patients in whom atherosclerosis has presented with a transient ischaemic attack (TIA), has been confined to a quantitative assessment of the luminal patency of the internal carotid artery. These traditional stratification parameters are no longer believed to be the most accurate predictors of a thrombo-embolism. This is because the process of vessel wall remodeling can maintain a luminal patency, and consequently, quite large friable plaques may remain unidentified. Accordingly, there is a need for an improved risk assessment. The fibrous cap of a vulnerable plaque is thinner, and an intraplaque hemorrhage and inflammation can occur during the development of atherosclerotic plaque. Several imaging methods for identifying vulnerable plaques have been developed. Recently, high resolution magnetic resonance (MR) imaging has emerged as an accurate non-invasive tool that can characterize the carotid plaque components in vivo. A High resolution carotid magnetic resonance is capable of distinguishing an intact, thick fibrous cap from a thin and ruptured cap in carotid plaque. In addition, a plaque MR can identify the active inflammation and detect a hemorrhage. High resolution carotid MR imaging is a valuable noninvasive method for quantifying the plaque components and identifying vulnerable plaque.

Noninvasive atherosclerosis imaging for predicting cardiovascular events and assessing therapeutic interventions.

Noninvasive assessment of atherosclerosis offers an opportunity to provide individual cardiovascular risk management and an opportunity to monitor the efficacy of therapy targeted toward atherosclerosis. The three imaging modalities that currently hold the most promise at the clinical and research levels are ultrasound for carotid intima-media thickness, computed tomography for coronary artery calcification, and magnetic resonance imaging for carotid and aortic plaque imaging. The following review describes the evidence that validates each technique as a surrogate marker of atherosclerosis, with an emphasis on cardiovascular events and the progression of disease. Both the particular strengths and limitations of each imaging modality are discussed.

Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques.

The correlation of B-mode ultrasonographic morphology with histologic characteristics of atherosclerotic carotid plaques remains ill-defined. The classification of plaques with recently reported measures of plaque echogenicity and heterogeneity has been unsatisfactory. We used computer-assisted duplex ultrasound (DU) scan image analysis to determine echogenicity of specific tissues in control subjects. This information was used to quantify each tissue in imaged carotid plaques with pixel distribution analysis (PDA). These objective observations then were quantitatively compared with plaque histology in symptomatic and asymptomatic patients. We performed standardized DU scanning of healthy tissues in 10 volunteer subjects and of 20 carotid artery plaques (7 symptomatic and 13 asymptomatic) in 19 patients with carotid stenosis. The plaques underwent histologic analysis after carotid endarterectomy. The grayscale intensity ranges of blood, lipid, fibromuscular tissue, and calcium were calculated in the control subjects. With computer-assisted image analysis, B-mode images of plaques were linearly scaled to normalize data. Pixel distribution within the images then was analyzed. The grayscale ranges of known tissues obtained from control subjects helped define the amount of intraplaque hemorrhage, lipid, fibromuscular tissue, and calcium within carotid plaque images. This analysis was correlated with tissue composition measurements on histologic sections of excised plaques. The median grayscale intensity (range) in control subjects was 2 (0 to 4) for blood, 12 (8 to 26) for lipid, 53 (41 to 76) for muscle, 172 (112 to 196) for fibrous tissue, and 221 (211 to 255) for calcium. PDA-derived predictions for blood, lipid, fibromuscular tissue, and calcium within carotid plaques correlated significantly with the histologic estimates of each tissue respectively (blood: P =.012; lipid: P =.0006; fibromuscular: P =.035; and calcium: P =.0001). A significantly higher amount of blood and lipid was seen within symptomatic plaques compared with asymptomatic ones (P =.0048 and P =.026, respectively). Conversely, a larger amount of calcification was noted within asymptomatic plaques (P =.0002). Computer-assisted PDA of DU scan images accurately quantified intraplaque hemorrhage, fibromuscular tissue, calcium, and lipid. Symptomatic plaques had lower calcium content but larger amounts of intraplaque hemorrhage and lipid. Quantitative PDA may be used to determine carotid plaque tissue composition to assist in the identification of symptomatic and potentially unstable asymptomatic plaques.

A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke

Atherosclerosis leading to stenosis of the internal carotid artery is the underlying cause of 8–15% of ischaemic strokes (symptomatic carotid stenosis). 1–2% of the adult population have asymptomatic carotid stenosis. Clinical trials in patients with symptomatic carotid stenosis showed a higher procedural risk of non-disabling stroke with stenting versus endarterectomy, but a higher risk of myocardial infarction, cranial nerve palsy, and access site haematoma with endarterectomy. Apart from procedural complications, both treatments are equally effective in preventing stroke and recurrent severe carotid stenosis in the medium-to-long term. Endarterectomy has a modest effect in preventing stroke among patients with asymptomatic carotid stenosis, whereas the role of stenting remains to be established. With advances in medical therapy against atherosclerosis, benefit from invasive therapy has become uncertain. Risk modelling, with the inclusion of brain and carotid plaque imaging, will become increasingly important in selecting patients for interventions.

Real-time spatial compound imaging improves reproducibility in the evaluation of atherosclerotic carotid plaques

Compound imaging has the ability of reducing speckle and clutter artifacts demonstrated in in vitro studies compared to conventional, single-angle imaging. We investigated intra- and interobserver agreement of 38 outlines of carotid artery plaque images acquired by these techniques, by measuring the overlapping area after repeated outlines. In general, both techniques showed good agreement. When considering the images with poorest overlap, compound imaging had a significant advantage over conventional imaging regarding both intra- and interobserver agreement. The interobserver variation for the overlapping area after two outlines was 20% for conventional technique and 10% for compound. The interobserver variation of the gray scale median value (GSM) for conventional technique ranged from −32 to +20 and from −6 to +6 for compound. Likewise, the coefficient of repeatability for the GSM value was 13 for conventional imaging and three for compound imaging, and interobserver variation for the GSM value for the overlapping area was 34% and 9% for conventional and compound technique. In conclusion, compound imaging improves intra- and interobserver agreement and reduces interobserver variation in the GSM value in a clinical setting. (E-mail: stko@gentoftehosp.kbhamt.dk)

An objective method for grading ultrasound images of carotid artery plaques

Plaque composition may improve identification of patients at risk of stroke. A new method of grading ultrasound (US) images to assess plaque composition is described. B-mode US images were obtained from 50 carotid specimens. Image analysis parameters were entered into a discriminant analysis package and compared retrospectively with histology. Discriminant functions were derived and then applied prospectively to image-analysis data obtained from a further 50 plaque specimens. For the prospective analysis, US images were graded according to the relative contribution of calcium, fibrous tissue, haemorrhage and lipid. The accuracy for retrospective classification of calcium was 100%, for fibrous tissue 97%, for lipid 76% and 68% for haemorrhage (κ = 0.81). Prospective classification showed an overall agreement of 65% (κ = 0.47). Significant intraplaque haemorrhage was identified with an 81% sensitivity and 83% specificity. The US method described demonstrated improved accuracy compared to previous studies. Further study is required to establish the use of this method for in vivo images and its correlation with patient symptoms. (E-mail: soundrie.padayachee @kcl.ac.uk)

Carotid plaque characterization by magnetic resonance imaging: review of the literature.

Magnetic resonance imaging (MRI) of carotid plaque has undergone significant improvements in the last decade. Early studies utilizing ex vivo specimens and spin-echo or fast spin-echo imaging led to the conclusion that T2 weighting is the best single contrast to characterize carotid plaque morphology. On these images, the fibrous plaque appears bright and the lipid core is dark; thrombus can have variable intensity. There can be an overlap in T2-weighted signal intensities among the various plaque components, which can be partially offset by the use of multispectral analysis of multiple contrast images. With improvements in coil design, sequence design, and main field and gradient capabilities, accurate in vivo differentiation and measurement of these various carotid plaque components should be possible in 3 to 5 years. Ex vivo and in vivo studies have yielded high-resolution measurements of the complex three-dimensional lumen geometry, which are being used to predict hemodynamic forces acting on the lumenal surface. Carotid plaque burden can be accurately measured in vivo today; ongoing longitudinal studies should lead to a better understanding of the relationship between plaque burden and the risk of thromboembolic complications, as well as the effect of diet and drug therapy in hyperlipidemic patients. With these developments in place or soon to be available, MRI of the diseased carotid artery wall may prove to be even more important than magnetic resonance angiography.

Spiral computed tomographic imaging related to computerized ultrasonographic images of carotid plaque morphology and histology.

Echolucency of carotid atherosclerotic plaques, as evaluated by computerized B-mode ultrasonographic images, has been associated with an increased incidence of brain infarcts on cerebral computed tomographic scans. We tested the hypotheses that characterization of carotid plaques on spiral computed tomographic images correlates with that on computerized B-mode ultrasonographic images and that spiral computed tomographic imaging predicts the histomorphometric plaque content. The study included 38 patients with neurologic symptoms and at least 50% stenosis of the ipsilateral carotid artery. High-resolution B-mode ultrasonographic images and spiral computed tomographic images of carotid plaques were computer processed to yield a quantitative measure, the gray scale level of the plaque. The mean Hounsfield value for spiral computed tomographic images correlated with the gray scale median for B-mode ultrasonographic images (univariate linear regression analysis: r = 0.45; P = .01) and the histologic content of calcification in the plaque (r = 0.34; P = .04) but not with lipid, hemorrhage, or fibrous tissue in the plaque. Spiral computed tomographic imaging seems to correlate with B-mode ultrasonographic imaging for showing plaque characteristics. Spiral computed tomographic attenuation was also correlated with the amount of calcification noted on histologic examination but not with lipid and hemorrhage, the components thought to characterize vulnerable, rupture-prone plaques.

Echo-lucency of computerized ultrasound images of carotid atherosclerotic plaques are associated with increased levels of triglyceride-rich lipoproteins as well as increased plaque lipid content.

Echo-lucency of carotid atherosclerotic plaques on computerized ultrasound B-mode images has been associated with a high incidence of brain infarcts as evaluated on CT scans. We tested the hypotheses that triglyceride-rich lipoproteins in the fasting and postprandial state predict carotid plaque echo-lucency and that echo-lucency predicts a high plaque lipid content. The study included 137 patients with neurological symptoms and > or = 50% stenosis of the relevant carotid artery. High-resolution B-mode ultrasound images of carotid plaques were computer processed to yield a measure of echogenicity (gray-scale level). Lipoproteins were measured before and hourly for 4 hours after a standardized fatty meal. A subgroup of 58 patients underwent endarterectomy. On linear regression analysis, echo-lucency (low gray-scale level) was associated with elevated levels of fasting and postprandial plasma triglycerides (P=.0002 and P=.002), IDL cholesterol (P=.0009 and P=.006), and VLDL/chylomicron remnant cholesterol (P=.0003 and P=.0004) and triglycerides (P=.0003 and P=.003), the area under the plasma triglyceride curve 0 to 4 hours after a fatty meal (P=.001), and body mass index (P=.0001). On ANCOVA, body mass index, fasting IDL cholesterol, and fasting plasma triglycerides were independent predictors of echo-lucency. Echo-lucency was associated with increased relative plaque lipid content (P=.02). Increased plasma levels of triglyceride-rich lipoproteins predict echo-lucency of carotid plaques, which is associated with increased plaque lipid content. Because echo-lucency has been associated with a high incidence of brain infarcts on CT scans, triglyceride-rich lipoproteins may predict a plaque type particularly vulnerable to rupture.

4.P.234 Low gray scale values of computerized images of carotid plaques associated with increases levels of triglyceride-rich lipoproteins and with increased plaque lipid content

4.P.234 Low gray scale values of computerized images of carotid plaques associated with increases levels of triglyceride-rich lipoproteins and with increased plaque lipid content

Ultrasound densitometric analysis of carotid plaque composition. Pathoanatomic correlation.

The components of a carotid artery plaque might affect the risk of ipsilateral stroke. The accuracy of carotid duplex scan in assessing stroke risk reflects the experience of the scan reader. Thus, methods that can enhance ultrasonic evaluation of plaque morphology might allow a more objective means of determining carotid-mediated stroke risk. We performed densitometric analysis of B-mode images of carotid plaques in nine patients scheduled for carotid endarterectomy. All patients had preoperative duplex color imaging and cerebral arteriography. The surgical specimen was analyzed histologically to determine the plaque components (soft plaque/organized thrombus, intraplaque hemorrhage/lipid deposition, fibrosis, and calcification). The specimen findings were correlated with the densitometric measurements to determine whether the density analysis would allow a reliable determination of the plaque substratum. With 1.0 as a reference point for the moving column of blood, the mean acoustic densities (+/-SD) were as follows: organized thrombus, 1.8 +/- 0.5; intraplaque hemorrhage/lipid deposition, 5.15 +/- 0.9; fibrosis, 9.51 +/- 2.9; and calcification, 15.5 +/- 8.6. We conclude that densitometric evaluation allows differentiation of the various possible components of carotid plaque. The determination of plaque composition, based on density measurement, may provide information about its potential for thromboembolization.

Three dimensional ultrasound imaging of carotid artery plaques: Steinke W, Hennerici M. J Cardiovasc Tech 1989;8:15–22

Three dimensional ultrasound imaging of carotid artery plaques: Steinke W, Hennerici M. J Cardiovasc Tech 1989;8:15–22