Atherosclerotic Plaque Components Research Articles

Incremental Prognostic Value of Different Components of Coronary Atherosclerotic Plaque at Cardiac CT Angiography beyond Coronary Calcification in Patients with Acute Chest Pain: Nance JW Jr, Schlett CL, Schoepf UJ, et al. Radiology 2012;264:679–90.

In this single-centered, retrospective cohort study of 458 low-to-intermediate-risk patients presenting with acute onset chest pain and without acute coronary syndrome or non-cardiac etiology of their symptoms on initial work-up, the authors investigated the value of coronary artery calcium (CAC) score and cardiac computed tomography (CT) angiography in predicting the risk for major adverse coronary events (MACE). Of the 458 patients included in the analysis, 70 (15%) had a MACE during the 24-month follow-up period.

Magnetic Resonance Imaging of Carotid Atherosclerosis and the Risk of Stroke

Stroke attributable to carotid atherosclerosis is a leading cause of mortality and morbidity. The clinical management of carotid atherosclerosis presently relies on the degree of stenosis determined by angiography. Degree of stenosis is limited in stratifying patients’ risk of stroke. Advances in magnetic resonance imaging have resulted in the ability to directly assess atherosclerotic plaque components, morphology, and biomechanical stress levels. Components of atherosclerosis, including lipid-rich necrotic core, fibrous cap thickness/disruption, and intraplaque hemorrhage, are promising emerging indicators of stroke. Information beyond luminal stenosis from magnetic resonance imaging may allow for improved detection of patients at risk of stroke from carotid atherosclerosis. We review the recent literature on the relationship of magnetic resonance imaging detected plaque components and cerebrovascular events. Clinical applications of magnetic resonance imaging of carotid plaque components are discussed.

Imaging Atherosclerotic Plaques with MRI: Role of Contrast Agents

Magnetic resonance imaging (MRI) represents one of the most promising techniques for noninvasive evaluation of atherosclerotic plaques. During the last 10 years, acquisition techniques dedicated to vascular wall imaging have been developed for MRI and offer images with high spatial resolution atherosclerotic plaques in the aorta and carotid arteries. Major components of atherosclerotic plaques can be identified based on differences in their intrinsic contrast with MRI. In addition to morphologic aspects, detection of biological activities in atherosclerotic plaques with MRI could bring new hints for the identification of high-risk plaques. A large array of MR contrast agents has become available during the last 10 years and tested for the evaluation of atherosclerotic plaques. In this review, we will discuss the advantages and drawbacks of several classes of MR contrast agents developed for atherosclerotic plaque imaging using representative examples.

Intracoronary Monocyte Chemoattractant Protein 1 and Vascular Endothelial Growth Factor Levels Are Associated with Necrotic Core, Calcium and Fibrous Tissue Atherosclerotic Plaque Components: An Intracoronary Ultrasound Radiofrequency Study

Aims: To investigate the relationship between various serum biomarkers and coronary atherosclerotic plaque composition obtained by intravascular ultrasound virtual histology (IVUS-VH). Methods: Using ELISA, we measured the serum levels of CD40 ligand, C-reactive protein, monocyte chemoattractant protein 1 (MCP-1), metalloproteinase 9, P-selectin and vascular endothelial growth factor (VEGF) in 40 patients with manifested coronary artery disease. Results: Correlation analysis between biomarkers levels, IVUS grayscale parameters and VH-defined necrotic core (NC), calcium, fibrous and fibrofatty components was performed. MCP-1 and VEGF levels correlated with the severity of area stenosis (r = 0.35, p = 0.03 and r = 0.38, p = 0.017, respectively) and inversely correlated with the remodeling index (r = –0.35, p = 0.03 and r = 0.35, p = 0.02, respectively). Higher levels of MCP-1 were associated with increased calcium (r = 0.47, p = 0.004), NC (r = 0.38, p = 0.02) and less fibrous tissue components (r = –0.34, p = 0.03), whereas VEGF had an inverse correlation with both calcium components (r = –0.37, p = 0.02) and NC (r = –0.34, p = 0.036) but was strongly associated with increased fibrous components (r = 0.47, p = 0.003). No significant correlation was noted for any of the other biomarkers. Conclusions: MCP-1 and VEGF serum levels in patients with ischemic heart disease are correlated with coronary artery plaque burden and composition.

Incremental Prognostic Value of Different Components of Coronary Atherosclerotic Plaque at Cardiac CT Angiography beyond Coronary Calcification in Patients with Acute Chest Pain

To systematically evaluate the incremental predictive value of cardiac computed tomographic (CT) angiography beyond the assessment of coronary artery calcium (CAC) in patients who present with acute chest pain but without evidence of acute coronary syndrome (ACS). The human research committee approved this study and waived the need for individual written informed consent. The study was HIPAA compliant. A total of 458 patients (36% male; mean age, 55 years ± 11) with acute chest pain at low to intermediate risk for coronary artery disease underwent coronary calcification assessment with cardiac CT angiography. All patients who did not experience ACS at index hospitalization were followed for instances of a major adverse cardiac event (MACE), such as a myocardial infarct, revascularization, cardiac death, or angina requiring hospitalization. CAC score and cardiac CT angiography were used to derive the presence and extent of atherosclerotic plaque (calcified, noncalcified, or mixed), and obstructive lesions (>50% luminal narrowing) were related to outcomes by using univariate and adjusted Cox proportional hazards models. Of the 458 patients, 70 (15%) experienced MACE (median follow-up, 13 months). Patients with no plaque at cardiac CT angiography remained free of events during the follow-up period, while 11 (5%) of 215 patients with no CAC had MACE. The extent of plaque was the strongest predictor of MACE independent of traditional risk factors (hazard ratio [HR], 151.77 for four or more segments containing plaque as compared with those containing no plaque; P < .001). Patients with mixed plaque were more likely to experience MACE (HR, 86.96; P = .002) than those with exclusively noncalcified plaque (HR, 58.06; P = .005) or exclusively calcified plaque (HR, 32.94; P = .02). The strong prognostic value of cardiac CT angiography is incremental to its known diagnostic value in patients with acute chest pain without ACS and is independent of traditional risk factors and CAC.

Spectral CT of carotid atherosclerotic plaque: comparison with histology

To distinguish components of vulnerable atherosclerotic plaque by imaging their energy response using spectral CT and comparing images with histology. After spectroscopic calibration using phantoms of plaque surrogates, excised human carotid atherosclerotic plaques were imaged using MARS CT using a photon-processing detector with a silicon sensor layer and microfocus X-ray tube (50 kVp, 0.5 mA) at 38-μm voxel size. The plaques were imaged, sectioned and re-imaged using four threshold energies: 10, 16, 22 and 28 keV; then sequentially stained with modified Von Kossa, Perl's Prussian blue and Oil-Red O, and photographed. Relative Hounsfield units across the energies were entered into a linear algebraic material decomposition model to identify the unknown plaque components. Lipid, calcium, iron and water-like components of plaque have distinguishable energy responses to X-ray, visible on spectral CT images. CT images of the plaque surface correlated very well with histological photographs. Calcium deposits (>1,000 μm) in plaque are larger than iron deposits (<100 μm), but could not be distinguished from each other within the same voxel using the energy range available. Spectral CT displays energy information in image form at high spatial resolution, enhancing the intrinsic contrast of lipid, calcium and iron within atheroma. Spectral computed tomography offers new insights into tissue characterisation. Components of vulnerable atherosclerotic plaque are spectrally distinct with intrinsic contrast. Spectral CT of excised atherosclerotic plaques can display iron, calcium and lipid. Calcium deposits are larger than iron deposits in atheroma. Spectral CT may help in the non-invasive detection of vulnerable plaques.

Automated Versus Manual In Vivo Segmentation of Carotid Plaque MRI

Automatically identifying carotid plaque composition using MR imaging remains a challenging task in vivo. The purpose of our study was to compare the detection and quantification of carotid artery atherosclerotic plaque components based on in vivo MR imaging data using manual and automated segmentation. Sixty patients from a multicenter study were split into a training group (20 patients) and a study group (40 patients). Each MR imaging study consisted of 4 high-resolution carotid wall sequences (T1, T2, PDw, TOF). Manual segmentation was performed by delineation of the vessel wall and different plaque components. Automated segmentation was performed in the study group by a supervised classifier trained on images from the training group of patients. For the detection of plaque components, the agreement between the visual and automated analysis was moderate for calcifications (κ = 0.59, CI 95% [0.36-0.82]) and good for hemorrhage (0.65 [0.42-0.88]) and lipids (0.65 [0.03-1.27]). For quantification of plaque volumes, the intraclass correlation was high for hemorrhage (0.80 [0.54-0.92]) and fibrous tissue (0.80 [0.65-0.89]), good for lipids (0.65 [0.43-0.80]), and poor for calcifications. In 40 patients with carotid stenosis, our results indicated that it was possible to automatically detect carotid plaque components with substantial or good agreement with visual identification, and that the volumes obtained manually and automatically were reasonably consistent for hemorrhage and lipids but not for calcium.

Role of macrophage scavenger receptors in atherosclerosis

Accumulating evidence indicates that atherosclerosis is a chronic inflammatory disease. The key innate immune cells that are involved in the pathogenesis of atherosclerosis are circulating monocytes and plaque macrophages. Complex interplay between immune and metabolic processes results in pathological activity of these cells. The best understood pathological process mediated by macrophages is their inability to process modified lipoproteins properly resulting in the formation of foamy cells, which are a dangerous component of atherosclerotic plaques. Key molecules involved in the recognition and processing of modified lipoproteins are scavenger receptors (SR). This is a large family of surface expressed structurally heterogeneous receptors with a broad spectrum of endogenous and exogenous ligands. The common functional feature of SR is internalisation of extracellular components and targeting them for lysosomal degradation. However, these relatively simple functions can have complex consequences, since they are linked to diverse specific signalling pathways and to other membrane transport pathways. Moreover, scavenger receptors can co-operate with other types of receptors increasing the variability of the macrophage response to multiple extracellular ligands. At least some SRs respond to modified lipoproteins by amplification of inflammation and accumulation of macrophages in the plaque, while some SRs may support tolerogenic reactions. Outcome of different SR activities will be the decision of monocytes and macrophage to guard homeostatic balance, support atherosclerosis progression and plaque instability by inflammatory reactions, or support rapid fibrotic processes in the plaque that stabilise it. Despite the accumulating knowledge about the molecular mechanisms of scavenger receptor action, their role in the progression of atherosclerosis remains controversial. The activities of scavenger receptors that can contribute to each of these processes are a subject of current review.

Classification of human coronary atherosclerotic plaques with T1, T2 and Ultrashort TE MRI

Summary Multicontrast MRI with T1, T2 and Ultrashort TE (UTE) sequences is used to image atherosclerotic plaque in human coronary arteries. MRI classification of the plaques is compared with their histological classification and found to correlate extremely well. The addition of UTE MRI adds significant value to the imaging of human coronary artery plaque by MRI. Background The differentiation of atherosclerotic plaque components in the carotid arteries with MRI has been successfully demonstrated. The detection of plaque calcification by MRI, however has been challenging. In addition, few studies have evaluated the ability of MRI to characterize atherosclerotic plaques in human coronary arteries (1). Here we use a combination of T1, T2 and ultrashort TE (UTE) MRI to evaluate atherosclerotic plaques in fixed post-mortem human coronary arteries. We hypothesized that the addition of UTE to T1and T2 weighted MRI would allow both calcified and lipid rich plaques to be accurately detected and distinguished from one another. Methods Twenty eight plaques from human donor hearts with proven coronary artery disease were imaged on 9.4T horizontal bore MRI scanner (Biospec, Bruker). The specimens were imaged with a T1W 3D FLASH sequence (250 um isotropic resolution, TR/TE 30/2.5ms), a T2W Rare sequence (slice thickness 0.4 mm, in plane resolution 0.156mm, TR/TE 3000/40ms), and an UTE sequence (200-300um resolution, TE of 20us). Plaques showing selective hypointensity on T2W MRI were classified as lipid rich. Areas of hypointesnity on the T1W images but not the UTE images were classified as calcified. After MRI, the plaques were sectioned for histological characterization with a pentachrome stain, which was used as the gold standard readout. The histological sections were digitized and co-registered with the MR images for analysis. Results Plaque classification by MRI was performed by 4 readers who were blinded to the histological plaque classification. The sensitivity and specificity of MRI for the detection of plaque calcification were 100.0% and 90.0% respectively. The sensitivity and specificity of MRI for the detection of lipid rich necrotic cores were 90.0%, 75.0%, respectively. Good inter-observer agreement was found for plaque classification by MRI ( = 0.7829, p<0.0001). More importantly, MRI categorization of coronary artery plaques agreed well with the histological classification (weighted =0.6945, p<0.0001). An example of a lipid-rich necrotic plaque with calcification is shown in Figure 1. A fibrocalcific coronary artery plaque is shown in Figure 2. Conclusions MRI with T1, T2 and UTE contrast is able to accurately classify atherosclerotic plaques in human coronary arteries. This underscores the need to develop techniques to image the coronary artery wall in patients in vivo.

In-vivo T2 mapping of atherosclerotic plaques in carotid arteries

Summary The purpose of this study was to measure the T2 relaxation times of carotid atherosclerotic plaque components in-vivo at 3T and show the potential application of T2 mapping for plaque segmentation. Background Clinical studies that have measured plaque T2 times were mostly performed ex-vivo using a small number of plaques excised from different arterial locations and imaged at different field strength using a limited number of TEs. The Table shows that T2 measured in the lipidrich necrotic core (LRNC) was consistently shorter than T2 in fibrous tissue or in normal media, which showed similar values. The only two studies of carotid plaques showed a comparable T2 range for LRNC and fibrous tissue regardless of field strength difference. Methods 12 patients with stable atherosclerosis (9 males, 72±11 years) were imaged on a 3T scanner (Siemens TIM Trio). Ethics approval from local board was obtained and subjects gave informed consent. A multiple-SpinEcho (multi-SE) sequence (Spin-Echo_Multi-Contrast or SE_MC) with low SAR pulses acquired black-blood cross-sectional images of carotid arteries using a 4-channel surface coil and cardiac gating (TE=25.8-38.7-51.664.5-77.4-90.3-103.2ms, TR=2R-R, FOV=160×128mm2, matrix-size=320×256, slice-thickness=2mm, partialFourier=5/8). T2 was estimated for every voxel of the carotid wall by fitting a mono-exponential decay curve to the signal intensities at 7 TEs using non-linear leastsquares regression. Using a semi-automated method based on Bayes classifiers, T2 maps of carotid arteries were segmented in 4 tissue types: calcification; LRNC; fibrous tissue and normal media; intra-plaque haemorrhage. Histological validation was not available. AHA plaque classification was performed by two blinded reviewers on multi-contrast images acquired separately. Results

Estimation and comparison of osteopontin levels in plasma in subjects with healthy periodontium and generalized chronic periodontitis and its assessment after scaling and root planing.

Background:Osteopontin (OPN) is a bone matrix derivative, whose levels reflect active lesions of aggravated periodontal disease accompanied by alveolar bone resorption. OPN is also a component of human atherosclerotic plaque, suggesting a role of OPN in cardiovascular diseases. The present study was conducted to assess and compare plasma OPN levels in subjects with healthy periodontium and generalized chronic periodontitis and to evaluate the effect of scaling and root planing on Plasma OPN levels of generalized chronic periodontitis subjects.Materials and Methods:40 gender matched subjects were divided into two equal groups, Group I- Healthy and Group II- Generalized chronic periodontitis, based on the Periodontal Disease Index. Blood samples were collected from the subjects at the time of clinical examination (Group I, II) and two months after Scaling and Root planning of Group II. Plasma OPN level was determined using a OPN Enzyme Immunometric Assay Kit (Quantikine).Results:The mean value of plasma OPN levels in subjects with generalized chronic periodontitis was higher (153.08 ng/ml) as compared to the subjects with Healthy periodontium (55.09 ng/ml). After treatment of generalized chronic periodontitis group, the level of plasma OPN decreased to 91.53 ng/ml.Conclusion:The findings from the study suggest that Plasma OPN levels were highest in plasma from sites with periodontal destruction; however, scaling and root planing resulted in the reduction of OPN levels.

Segmentation of carotid plaque using multicontrast 3D gradient echo MRI

To evaluate the performance of automatic segmentation of atherosclerotic plaque components using solely multicontrast 3D gradient echo (GRE) magnetic resonance imaging (MRI). A total of 15 patients with a history of recent transient ischemic attacks or stroke underwent carotid vessel wall imaging bilaterally with a combination of 2D turbo spin echo (TSE) sequences and 3D GRE sequences. The TSE sequences included T1-weighted, T2-weighted, and contrast-enhanced T1-weighted scans. The 3D GRE sequences included time-of-flight (TOF), magnetization-prepared rapid gradient echo (MP-RAGE), and motion-sensitized driven equilibrium prepared rapid gradient echo (MERGE) scans. From these images, the previously developed morphology-enhanced probabilistic plaque segmentation (MEPPS) algorithm was retrained based solely on the 3D GRE sequences to segment necrotic core (NC), calcification (CA), and loose matrix (LM). Segmentation performance was assessed using a leave-one-out cross-validation approach via comparing the new 3D-MEPPS algorithm to the original MEPPS algorithm that was based on the traditional multicontrast protocol including 2D TSE and TOF sequences. Twenty arteries of 15 subjects were found to exhibit significant plaques within the coverage of all imaging sequences. For these arteries, between new and original MEPPS algorithms, the areas per slice exhibited correlation coefficients of 0.86 for NC, 0.99 for CA, and 0.80 for LM; no significant area bias was observed. The combination of 3D imaging sequences (TOF, MP-RAGE, and MERGE) can provide sufficient contrast to distinguish NC, CA, and LM. Automatic segmentation using 3D sequences and traditional multicontrast protocol produced highly similar results.

Cholesterol Acyltransferase Gene Mutations Have Accelerated Atherogenesis as Assessed by Carotid 3.0-T Magnetic Resonance Imaging: Carriers of Lecithin

The aim of this study was to investigate the role of reduced lecithin: cholesterol acyltransferase (LCAT) function on atherogenesis using 3.0-T carotid magnetic resonance imaging (MRI) and B-mode ultrasound. The role of low high-density lipoprotein cholesterol as a causal factor in atherogenesis has recently been questioned. LCAT plays a key role in high-density lipoprotein cholesterol metabolism. Carotid 3.0-T MRI and B-mode ultrasound measurements were performed in 40 carriers of LCAT gene mutations and 40 controls, matched for age. Patients with cardiovascular disease were excluded. Carriers had 31% lower LCAT activity levels and 38% decreased high-density lipoprotein cholesterol levels (both p < 0.001 vs. controls). Carriers presented with a 10% higher normalized wall index (0.34 ± 0.07 vs. 0.31 ± 0.04, p = 0.002), a 22% higher mean wall area (17.3 ± 8.5 mm2 vs. 14.2 ± 4.1 mm2, p = 0.01), and a 22% higher total wall volume (1,039 ± 508 mm3 vs. 851 ± 247 mm3, p = 0.01 vs. controls) as measured by MRI. The prevalence (20 vs. 5, p = 0.002) and the total volume (102 mm3 vs. 3 mm3) of atherosclerotic plaque components on MRI relating to lipid-rich tissue or calcification were also higher in carriers than in controls. All differences retained significance after adjustment for age, sex, blood pressure, low-density lipoprotein cholesterol, body mass index, smoking, and family history of cardiovascular disease. Common carotid intima-media thickness measured with ultrasound was increased in carriers by 12.5% (0.72 ± 0.33 mm vs. 0.64 ± 0.15 mm, p = 0.14). Carriers of LCAT gene mutations exhibit increased carotid atherosclerosis, indicating an increased risk of cardiovascular disease. The present findings imply that increasing LCAT activity may be an attractive target in cardiovascular prevention strategies.

Abstract 17244: Monocytes and Oxidized Lipids Promote the Destabilization of Calcified Plaque Via Matrix Metalloproteinases(MMP)

Objective: Vascular calcification is closely associated with atherosclerosis, but whether it mechanically affects plaque stability remains controversial. We previously showed that calcific nodules produced with cultured calcifying vascular cells (CVC) were destabilized in response to shear stress. Here, we characterized the CVC-derived calcified nodules in ApoE-null mice, and assessed oxLDL and monocytes on the destabilization of CVC-derived calcified nodules under pulsatile shear stress (PSS). Methods and Results: To demonstrate that CVC-derived calcified nodules contain components of calcific atherosclerotic plaque in vivo, CVC was implanted in the ApoE-null mice via a cage. After 6 weeks, histology and immunohistochemsitry revealed a calcified plaque-like structure with fibrous caps, lipids, Collagen II, alkaline phosphotase and friable shoulders. To investigate the calcific nodule destabilization in vitro , CVC nodules were subjected to PSS for two and one-half hours. The percentage of nodules detached was calculated as quantification of nodule destabilization. Computational Fluid Dynamic (CFD) code simulated the instantaneous shear force distribution on the individual nodules and demonstrated accentuated instantaneous shear forces on the shoulder regions of nodules. Treatment with oxLDL or co-culture with monocytic THP-1 cells promoted the destabilization of nodules(Nodules detached: control (PSS) = 24±3%, PSS + THP-1=57±6%, PSS + oxLDL=45±7%, n=4, P &lt;0.001). Both oxLDL and THP-1 significantly up-regulated the expression of MMP-1, MMP-3 and MMP-9 in CVC, and increased the activities of MMP. MMP inhibitor, GM6001, significantly reversed oxLDL- and THP-1-induced nodule destabilization, whereas over-expression of MMP9 increased nodule destabilization. Conclusion: These findings revealed that calcific CVC nodules resembled atherosclerotic plaque in vivo , and active lipids and monocytes induced CVC nodules to express MMP, promoting destabilization of the calcified nodules. This study provides a dynamic model to characterize the destabilization of calcific atherosclerotic plaque in vitro .

Classification of noncalcified coronary atherosclerotic plaque components on CT coronary angiography: impact of vascular attenuation and density thresholds

The authors assessed the effect of vascular attenuation and density thresholds on the classification of noncalcified plaque by computed tomography coronary angiography (CTCA). Thirty patients (men 25; age 59 ± 8 years) with stable angina underwent arterial and delayed CTCA. At sites of atherosclerotic plaque, attenuation values (HU) were measured within the coronary lumen, noncalcified and calcified plaque material and the surrounding epicardial fat. Based on the measured CT attenuation values, coronary plaques were classified as lipid rich (attenuation value below the threshold) or fibrous (attenuation value above the threshold) using 30-HU, 50-HU and 70-HU density thresholds. One hundred and sixty-seven plaques (117 mixed and 50 noncalcified) were detected and assessed. The attenuation values of mixed plaques were higher than those of exclusively noncalcified plaques in both the arterial (148.3 ± 73.1 HU vs. 106.2 ± 57.9 HU) and delayed (111.4 ± 50.5 HU vs. 64.4 ± 43.4 HU) phases (p<0.01). Using a 50-HU threshold, 12 (7.2%) plaques would be classified as lipid rich on arterial scan compared with 28 (17%) on the delayed-phase scan. Reclassification of these 16 (9.6%) plaques from fibrous to lipid rich involved 4/30 (13%) patients. Classification of coronary plaques as lipid rich or fibrous based on absolute CT attenuation values is significantly affected by vascular attenuation and density thresholds used for the definition.

Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol esters in human peripheral vascular lesions

Although LDL is rendered proatherogenic by various experimental treatments (e.g., acetylation), the exact structural changes that drive LDL transformation in vivo remain enigmatic. Among the many hypothesized targets of oxidative modification are cholesterol esters (CE). This family of neutral lipids, which carries a highly unsaturated pool of fatty acyl groups, is the main component of both LDL particles and atherosclerotic plaques. Tandem mass spectrometry (MS/MS) was employed to reveal abundant and diverse oxidized CEs (oxCE), including novel oxidation products, within human peripheral vascular lesions. These oxCE species composed up to 40% of the total CE pool, with cholesteryl linoleate being oxidized to the greatest extent. Imaging mass spectrometry studies showed that oxCE was entirely confined within the plaque, along with unmodified CE and triacylglyceride (TAG). Interestingly, we found no evidence for TAG oxidation, although polyunsaturated species were abundant. Enzymatic oxidation of cholesteryl linoleate by 15-lipoxygenase (15-LO), an enzyme often invoked in CE oxidation, initially results in a regio- and stereospecific product. Analysis of intact cholesteryl hydroxyoctadecadienoate isomers in human atheromata revealed no regio- or stereospecificity, indicating 15-LO was either not a major source of oxCE or nonenzymatic processes had eroded any product specificity.

Identification of Atherosclerotic Plaque Components in Carotid Arteries with Ultrasound Elastography. A Pilot Study.

Identification of Atherosclerotic Plaque Components in Carotid Arteries with Ultrasound Elastography. A Pilot Study.

Beneficial effect of anti-platelet therapies on atherosclerotic lesion formation assessed by phase-contrast X-ray CT imaging

We have applied an imaging system of phase-contrast X-ray CT to the detection of atherosclerotic plaque components by means of the differences of tissue mass densities. In this study, we investigated the effect of the anti-platelet therapies, widely used for secondly prevention of cardiovascular events, on plaque stability and examined whether this novel technique could detect the changes of plaque components under the therapy. Apolipoprotein E-deficient mice were fed on high-cholesterol diet alone and either with 0.1% cilostazol or clopidogrel for 10 weeks. We assessed atherosclerotic lesion volumes and components at brachiocephalic artery by the phase-contrast X-ray CT imaging and histochemistry. The phase-contrast X-ray CT imaging could reveal that cilostazol and clopidogrel significantly decreased atherosclerotic lesion volumes at brachiocephalic artery (31.2% reduction in cilostazol group and 37.4% reduction in clopidogrel group), compared with control group. In addition, the mass densities calculated by this method revealed the anti-platelet treatment increased stable plaque areas including high collagen content, but decreased unstable plaque areas including lipid and macrophage content. These findings were confirmed by histological analyses. Real-time PCR analyses indicated that anti-platelets inhibited gene expressions of cytokines and adhesion molecules, such as IFNγ and ICAM-1. Anti-platelet therapies had a beneficial effect on plaque stability maybe due to anti-inflammatory actions. Phase-contrast X-ray CT imaging could quantify the plaque volume and qualify the plaque components affected by anti-platelet therapies. This novel phase-contrast X-ray CT imaging system could be a plausible method to detect the unstable plaque non-invasively in the future.

113 Dual energy ct improves differentiation of coronary atherosclerotic plaque components compared to conventional single energy CT

<h3>Introduction</h3> Vulnerable plaques have a relatively high necrotic core area and low fibrous tissue content. Although CT can identify plaque components on the basis of their x-ray attenuation, there is significant overlap between their attenuation ranges, most crucially between necrotic core and fibrous plaque. Recently introduced dual energy CT (DECT) permits acquisition of 2 different energy data sets simultaneously, with the change in attenuation of plaque components to different energies depending upon their material composition. We therefore examined whether DECT was better than single energy CT in determining plaque components defined by virtual histology IVUS. <h3>Methods</h3> 20 patients underwent DECT and 3-vessel VH-IVUS. CT data was obtained at peak voltages of 100 kV and 140 kV. 52 plaques were chosen with either homogenous fibrous plaque or confluent areas of calcified plaque or necrotic core as defined by VH-IVUS. VH-IVUS images were co-registered and orientated with the corresponding CT images using distance from coronary ostia and fiduciary markers (Abstract 113 figure 1). Multiple regions of interest (ROI) were placed within the plaque components or in lumen on cross sectional CT images pre-classified by VH-IVUS (Abstract 113 figure 1). ROI densities were measured (in Hounsfield Units) and assigned to the plaque component. A dual energy index (DEI) was created for each component, defined as the ratio of the difference in attenuation at 2 different energies / sum of attenuation with 1000 added to each attenuation value to avoid negatives. <h3>Results</h3> Attenuation values for 1088 ROIs were measured from 70 paired data sets at 100 kV and 140 kV creating 70 DEIs (12 necrotic core, 11 fibrous plaque, 29 calcified plaques and 18 lumen). Values obtained using a single energy data set showed good differentiation between calcified plaque and all others (p&lt;0.05), but considerable overlap between necrotic core and fibrous plaque (p=ns) (Abstract 113 figure 2A) (Abstract 113 table 1). In DECT, lumen (iodinated contrast) showed the greatest change in attenuation and hence had the highest DEI. Necrotic core had the lowest DEI and could be distinguished from all other components (p&lt;000.1) Importantly, in contrast to the single energy data, DEI derived from both energy data sets permitted resolution of necrotic core and fibrous plaque without overlap (Abstract 113 figure 2B). <h3>Conclusions</h3> The additional attenuation data provided by DECT improves the differentiation of plaque components when compared to conventional single energy CT. In particular, DECT may allow better differentiation of necrotic core and fibrous plaque, a weakness of conventional cardiac CT, allowing for more accurate non-invasive identification of vulnerable plaques.

Automated versus manual segmentation of atherosclerotic carotid plaque volume and components in CTA: associations with cardiovascular risk factors

The purpose of this study was to validate automated atherosclerotic plaque measurements in carotid arteries from CT angiography (CTA). We present an automated method (three initialization points are required) to measure plaque components within the carotid vessel wall in CTA. Plaque components (calcifications, fibrous tissue, lipids) are determined by different ranges of Hounsfield Unit values within the vessel wall. On CTA scans of 40 symptomatic patients with atherosclerotic plaque in the carotid artery automatically segmented plaque volume, calcified, fibrous and lipid percentages were 0.97 ± 0.51 cm(3), 10 ± 11%, 63 ± 10% and 25 ± 5%; while manual measurements by first observer were 0.95 ± 0.60 cm(3), 14 ± 16%, 63 ± 13% and 21 ± 9%, respectively and manual measurement by second observer were 1.05 ± 0.75 cm(3), 11 ± 12%, 61 ± 11% and 27 ± 10%. In 90 datasets, significant associations were found between age, gender, hypercholesterolemia, diabetes, smoking and previous cerebrovascular disease and plaque features. For both automated and manual measurements, significant associations were found between: age and calcium and fibrous tissue percentage; gender and plaque volume and lipid percentage; diabetes and calcium, smoking and plaque volume; previous cerebrovascular disease and plaque volume. Significant associations found only by the automated method were between age and plaque volume, hypercholesterolemia and plaque volume and diabetes and fibrous tissue percentage. Significant association found only by the manual method was between previous cerebrovascular disease and percentage of fibrous tissue. Automated analysis of plaque composition in the carotid arteries is comparable with the manual analysis and has the potential to replace it.