Quantification Of Atherosclerotic Plaques Research Articles

Atherosclerosis evaluation and cardiovascular risk estimation using coronary computed tomography angiography.

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

Coronary artery calcium (CAC) score for cardiovascular risk stratification in a Thai clinical cohort: A comparison of absolute scores and age-sex-specific percentiles

PurposesCoronary artery calcium (CAC) score provides a quantification of atherosclerotic plaque within the coronary arteries. This study aimed to examine the prevalence and CAC score distribution and to evaluate the association of each CAC score classifications with major adverse cardiovascular events (MACE) in a Thai clinical cohort. MethodsThis study was a retrospective observational cohort. We included patients aged above 35 years who underwent CAC score testing. The absolute and age-sex specific percentile classifications were categorized as 0, 1 to 10, 11 to 100, 101 to 400, and >400 and 0, <75th, 75th – 90th, and >90th, respectively. The endpoint was MACE, including cardiovascular death, myocardial infarction, heart failure hospitalization, coronary artery revascularization procedure, and stroke. Multivariable Cox regression was used to estimate the hazard ratios. The discriminative performance between classifications were compared using Harrell's C-statistics. The agreement was assessed via Cohen's Kappa. ResultsThis study included 440 patients, with approximately 70% of Thai patients exhibiting a CAC score. CAC score distributed higher in male than female and increased with age. Both CAC score classification demonstrated the acceptable predictive performance. However, fair agreement was observed between classifications (Cohen's kappa 0.51, 95%CI 0.42–0.59). Within the absolute classification, a higher CAC score was associated with increased hazard ratios for MACE across stratified age-sex-specific percentile levels. In contrast, the hazard ratios for MACE did not consistently rise with higher age-sex-specific percentile CAC score when stratified by absolute CAC score levels. ConclusionsBoth absolute and age-sex-specific percentile CAC score demonstrated acceptable performance in predicting MACE. However, the absolute CAC score classification may be more suitable for risk stratification within the Thai clinical cohort. Our findings offer supportive information that could inform future recommendations for CAC score testing criteria within national clinical practice guidelines.

Computed tomography plaque analysis identifies residual inflammation in recent acute myocardial infarction patients

Abstract Introduction Residual inflammatory risk (RIR) following acute myocardial infarction (AMI) patients is associated with recurrent major adverse cardiovascular events. Atherosclerotic plaque quantification using computed tomographic coronary angiography (CTCA) can specifically identify inflamed plaque characteristics. We compared plaque burden and tissue composition in AMI patients with those of stable coronary artery disease (CAD) patients to identify imaging markers of RIR. Purpose We aimed to identify signs of residual inflammation in recent AMI patients via CTCA atheroma quantification. We hypothesised that recent AMI patients have plaque characteristics suggestive of inflammation. Methods 108 patients recruited from multiple sites with AMI &amp;lt;1 month were propensity-matched via CAD risk factors (age, gender, diabetes, hypertension, hyperlipidaemia, smoking and family history of CAD) with stable CAD patients in a 1:1 ratio. Propensity matched recent AMI and stable CAD patient cohorts had similar profiles: age (60±9.7 vs 57±10.0 years), gender (91.7% vs 92.6% male), diabetes (13.9% vs 15.7%), hypertension (44.4% vs 50.9%) and hyperlipidaemia (50.9% vs 63.9%, p&amp;gt;0.05 for all). Total plaque burden (total lesion volume/total vessel volume) and plaque composition (fibrous fatty [fibrofatty, FF, 31 – 130 HU], necrotic core [NC, -30 – 30 HU], fibrous [131 – 350 HU] and calcium [&amp;gt; 350 HU]) were extracted from CTCA scans and aggregated per patient. Culprit lesions of recent AMI patients were excluded from the analysis due to the fact that coronary stents would affect plaque characterisation. Multivariate linear regression, corrected for CAD risk factors, was used to compare these parameters between the two cohorts. Results Recent AMI patients and stable CAD patients had similar total plaque burden (β=0.001±0.013, p=0.950, Figure 1a). Patients with recent AMI had higher non-calcified plaque volume ratio (β=0.071±0.026, p&amp;lt;0.05, Figure 1b) due to higher FF (β=0.094±0.019, Figure 1d) and NC (β=0.025 ± 0.005, Figure 1e) plaque volume (p&amp;lt;0.05 for all), but less fibrous plaque volume (β = -0.048±0.019, p&amp;lt;0.05, Figure 1c). Conclusions Recent AMI patients had a greater non-calcified plaque burden than stable CAD patients due to larger FF and NC plaque burden. Since FF and NC components indicate ongoing inflammation in the plaque, while fibrous content indicates resolved inflammation; increased NC and FF burden suggest increased coronary plaque inflammation in non-culprit lesions of recent AMI patients, supporting the presence of residual inflammation in recent AMI patients.Figure 1

VWI-APP: Vessel wall imaging-dedicated automated processing pipeline for intracranial atherosclerotic plaque quantification.

Quantitative plaque assessment based on 3D magnetic resonance (MR) vessel wall imaging (VWI) has been shown to provide valuable numerical markers of the burden and risk of intracranial atherosclerotic disease (ICAD). However, plaque quantification is currently time-consuming and observer-dependent due to the demand for heavy manual effort. A VWI-dedicated automated processing pipeline (VWI-APP) is desirable. To develop and evaluate a VWI-APP for end-to-end quantitative analysis of intracranial atherosclerotic plaque. We retrospectively enrolled 91 subjects with ICAD (80 for pipeline development, 10 for an end-to-end pipeline evaluation, and 1 for demonstrating longitudinal plaque assessment) who had undergone VWI and MR angiography. In an end-to-end evaluation, diameter stenosis (DS), normalized wall index (NWI), remodeling ratio (RR), plaque wall contrast ratio (CR), and total plaque volume (TPV) were quantified at each culprit lesion using the developed VWI-APP and a computer-aided manual approach by a neuroradiologist, respectively. The time consumed in each quantification approach was recorded. Two-sided paired t-tests and intraclass correlation coefficient (ICC) were used to determine the difference and agreement in each plaque metric between VWI-APP and manual quantification approaches. There was no significant difference between VWI-APP and manual quantification in each plaque metric. The ICC was 0.890, 0.813, 0.827, 0.891, and 0.991 for DS, NWI, RR, CR, and TPV, respectively, suggesting good to excellent accuracy of the pipeline method in plaque quantification. Quantitative analysis of each culprit lesion on average took 675.7s using the manual approach but shortened to 238.3s with the aid of VWI-APP. VWI-APP is an accurate and efficient approach to intracranial atherosclerotic plaque quantification. Further clinical assessment of this automated tool is warranted to establish its utility in the risk assessment of ICAD lesions.

Atherosclerotic plaque characteristics on quantitative coronary computed tomography angiography associated with ischemia on positron emission tomography in diabetic patients

Patients with diabetes mellitus (DM) may show diffuse coronary artery atherosclerosis on coronary computed tomography angiography (CTA). The present study aimed at quantification of atherosclerotic plaque with CTA and its association with myocardial ischemia on positron emission tomography (PET) in DM patients. Of 922 symptomatic outpatients without previously known coronary artery disease who underwent CTA, 115 with DM (mean age 65 ± 8 years, 58% male) who had coronary atherosclerosis and underwent both quantified CTA (QCTA) and PET were included in the study. QCTA analysis was performed on a per-vessel basis and the most stenotic lesion of each vessel was considered. Myocardial ischemia on PET was based on absolute myocardial blood flow at stress ≤ 2.4 ml/g/min. Of the 345 vessels included in the analysis, 135 (39%) had flow-limiting stenosis and were characterized by having longer lesions, higher plaque volume, more extensive plaque burden and higher percentage of dense calcium (37 ± 22% vs 28 ± 22%, p = 0.001). On univariable analysis, QCTA parameters indicating the degree of stenosis, the plaque extent and composition were associated with presence of ischemia. The addition of the QCTA degree of stenosis parameters (x2 36.45 vs 88.18, p < 0.001) and the QCTA plaque extent parameters (x2 88.18 vs 97.44, p = 0.01) to a baseline model increased the association with ischemia. In DM patients, QCTA variables of vessel stenosis, plaque extent and composition are associated with ischemia on PET and characterize the hemodynamic significant atherosclerotic lesion.

Can Target-to-Background Ratio Measurement Lead to Detection and Accurate Quantification of Atherosclerosis With FDG PET? Likely Not.

The introduction of FDG in 1976 started a new discipline and enhanced the role of molecular imaging in medicine. While the initial intent with this tracer was to determine brain function in a variety of neuropsychiatric disorders, over time, this powerful approach has made a major impact on managing many other diseases and disorders. During the past 2 decades, FDG PET has been used to detect inflammatory lesions in the atherosclerotic plaques and in other settings. However, the suboptimal spatial resolution of PET limits its ability to visualize plaques that are very small in size. Furthermore, this tracer remains in the blood for an extended period and therefore provides suboptimal results. Target-to-background ratio (TBR) has been suggested to correct for this source of error. Unfortunately, TBR values vary substantially, depending on the timing of image acquisition. Delayed imaging at later time points (3–4 hours) may obviate the need for TBR measurement, but it is impractical with conventional PET instruments. Recently, 18F-sodium fluoride (NaF) has been used for detection and quantification of molecular calcification in the plaques. This tracer is highly specific for calcification and is rapidly cleared from the circulation. In addition, global atherosclerotic burden as measured by NaF PET can be determined accurately either in the heart or major arteries throughout the body. Therefore, the role of FDG PET–based TBR measurement for detection and quantification of atherosclerotic plaques is questionable at this time.

Automatic Quantification of Atherosclerosis in Contrast-Enhanced MicroCT Scans of Mouse Aortas Ex Vivo.

Objective While microCT evaluation of atherosclerotic lesions in mice has been formally validated, existing image processing methods remain undisclosed. We aimed to develop and validate a reproducible image processing workflow based on phosphotungstic acid-enhanced microCT scans for the volumetric quantification of atherosclerotic lesions in entire mouse aortas. Approach and Results. 42 WT and 42 apolipoprotein E knockout mouse aortas were scanned. The walls, lumen, and plaque objects were segmented using dual-threshold algorithms. Aortic and plaque volumes were computed by voxel counting and lesion surface by triangulation. The results were validated against manual and histological evaluations. Knockout mice had a significant increase in plaque volume compared to wild types with a plaque to aorta volume ratio of 0.3%, 2.8%, and 9.8% at weeks 13, 18, and 26, respectively. Automatic segmentation correlated with manual (r2 ≥ 0.89; p < .001) and histological evaluations (r2 > 0.96; p < .001). Conclusions The semiautomatic workflow enabled rapid quantification of atherosclerotic plaques in mice with minimal manual work.

Artificial Intelligence-based Plaque Quantification From Coronary Computed Tomography Angiography Using Deep Learning: External Validation And Comparison With Intravascular Ultrasound

Introduction: Atherosclerotic plaque quantification from coronary computed tomography angiography (CTA) enables accurate assessment of coronary artery disease burden, progression, and prognosis. However, quantitative plaque analysis is time-consuming and requires high expertise. We sought to develop and externally validate an artificial intelligence (AI)-based deep learning (DL) approach for CTA-derived measures of plaque volume and stenosis severity.

Deep Learning From Coronary Computed Tomography Angiography for Atherosclerotic Plaque and Stenosis Quantification and Cardiac Risk Prediction

Background: Atherosclerotic plaque quantification from coronary computed tomography angiography (CCTA) enables accurate assessment of coronary artery disease burden and prognosis. We sought to develop and externally validate a deep learning (DL) system for CCTA-derived measures of plaque volume and stenosis severity. Methods: This was an international multicenter study of patients undergoing CCTA at 11 sites. A novel DL convolutional neural network was trained to segment coronary plaque in 921 patients (5,045 lesions). The DL network was then applied to an independent test set, which included an external validation cohort of 175 patients (1,081 lesions) as well 50 patients (84 lesions) assessed by intravascular ultrasound (IVUS) within one month of CCTA. Thereafter, we evaluated the prognostic value of DL-based plaque measurements for fatal or nonfatal myocardial infarction (MI) in 1,611 patients from the prospective SCOT-HEART trial. Findings: In the overall test set, there was excellent agreement between DL and expert reader measurements of total plaque volume (intraclass correlation coefficient [ICC] 0·964) and percent diameter stenosis (ICC 0·879; both p<0.001). When compared with IVUS, there was excellent agreement for DL total plaque volume (ICC 0·949) and minimal luminal area (ICC 0·904). The average per-patient DL plaque analysis time was 5.7 seconds versus 25-30 minutes taken by experts. Over a median follow-up of 4·7 years, MI occurred in 41 patients (2·5%) from the SCOT-HEART trial. DL-based total plaque volume ≥238·5mm 3 was associated with an increased risk of MI (HR 5·36, 95% CI 1·70-16·86; p=0·004) after adjustment for the presence of DL-based obstructive stenosis (HR 2·49, 95% CI 1·07-5·50; p=0·009) and the cardiovascular risk score (HR 1·01, 95% CI 0·99-1·04; p=0·35). Interpretation: A novel externally validated DL system provides rapid measurements of plaque volume and stenosis severity from CCTA which agree closely with expert readers and IVUS and carry prognostic value for future MI. Funding: National Heart, Lung, and Blood Institute. Declaration of Interest: Outside of the current work, S.C., P.S., and D.D. received software royalties from Cedars-Sinai Medical Center. D.B, P.S., and D.D. hold a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization). All other authors have nothing to declare. Ethical Approval: This work was approved by the Institutional Review Boards and all patients provided written informed consent.

Stress Myocardial Perfusion Imaging vs Coronary Computed Tomographic Angiography for Diagnosis of Invasive Vessel-Specific Coronary Physiology

Stress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement. To compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR. Controlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018. Patients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and FFR by CT (FFR-CT), and semiquantitative scoring of rest/stress myocardial perfusion imaging (by magnetic resonance, positron emission tomography, or single photon emission CT). Multivariable generalized linear mixed models were derived and validated calculating the area under the receiver operating characteristics curve. The primary end point was invasive FFR of 0.80 or less. Of the 612 patients, the mean (SD) age was 64 (10) years, and 426 (69.9%) were men. An invasive FFR of 0.80 or less was measured in 26.5% of 1727 vessels. In the derivation cohort, CCTA vessel-specific factors associated with FFR 0.80 or less were stenosis severity, percentage of noncalcified atheroma volume, lumen volume, the number of lesions with high-risk plaque (≥2 of low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification), and the number of lesions with stenosis greater than 30%. Fractional flow reserve-CT was not additive to this model including stenosis and atherosclerotic plaque. Significant myocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P < .001). A comprehensive anatomic interpretation with CCTA, including quantification of obstructive and nonobstructive atherosclerotic plaque, was superior to functional imaging in the diagnosis of invasive FFR. Comprehensive CCTA measures improve prediction of vessel-specific coronary physiology more so than stress-induced alterations in myocardial perfusion. ClinicalTrials.gov Identifier: NCT02173275.

Reproducibility of 3.0T High-Resolution Magnetic Resonance Imaging for the Identification and Quantification of Middle Cerebral Arterial Atherosclerotic Plaques

Objective: To assess the reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of atherosclerotic plaques in the middle cerebral artery. Methods: Sixty-nine consecutive patients with ischemic stroke or asymptomatic stenosis (>30%) of the middle cerebral artery underwent 3.0T high-resolution magnetic resonance imaging examinations. Two independent investigators reviewed all images with 1 investigator re-evaluating all images 4 weeks later. Wall characteristics of the middle cerebral artery, including plaque surface morphology, plaque location, plaque components, and burden were identified and measured. Results: Intraobserver and interobserver agreement were all substantial in identifying plaque surface irregularity (k = 0.741, 0.555-0.897; k = 0.685, 0.490-0.843; respectively) and intraplaque hemorrhage (k = 0.654, 0.446-0.838; k = 0.605, 0.369-0.792; respectively). Intraobserver agreement was substantial (k = 0.654) and interobserver agreement was moderate (k = 0.553) for the identification of plaque fibrous caps. The total intraobserver and interobserver reproducibility was almost excellent for the identification of plaque position. With regards to vessel area measurement at the site of maximal lumen narrowing, intraobserver and interobserver reproducibility was excellent (intraclass correlation coefficient was 0.886 and 0.885, respectively) and moderate for lumen area at the site of maximal lumen narrowing (intraclass correlation coefficient was 0.695 and 0.558, respectively). In addition, intraobserver and interobserver reproducibility was excellent for vessel area and lumen area measurements at the reference sites. Conclusions: The reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of artery wall characteristics was overall acceptable. However, the reliability for lumen area measurement at the maximum narrowing site and identification of the fibrous cap needs to be improved.

Tiaopi huxin recipe improved endothelial dysfunction and attenuated atherosclerosis by decreasing the expression of caveolin-1 in ApoE-deficient mice.

The Tiaopi Huxin recipe (TPHXR) is widely used in traditional Chinese medicine for the clinical treatment of coronary heart disease. However, the mechanism of TPHXR treatment of atherosclerosis (AS) has not been fully elucidated. In this study, we have aimed to explore the potential antiatherosclerotic effect of TPHXR and its underlying mechanisms. Male ApoE knockout (ApoE-/- ) mice were fed a high-fat diet for 12 weeks and were randomly divided into four groups: the control group, and the low-dose, medium-dose, and high-dose TPHXR groups. The nitric oxide (NO) levels in arterial tissue and human umbilical vein endothelial cells (HUVECs) were measured bydiaminofluorescein-2 diacetate staining. Vasorelaxation of mice aorta was performed by wire myograph. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), hs-CRP, IL-6, and IL-1β, in mice plasma were analyzed by enzyme-linked immunosorbent assay. Western blot analysis was applied to observe protein expression. Oil Red O staining was utilized for the quantification of atherosclerotic plaques. Results showed that 4 weeks of high- and medium-dose TPHXR treatment by oral gavage reduced atheromatous lesions in ApoE -/- mice. The high- and medium-dose TPHXR treatment, but not the low-dose treatment, promoted eNOS phosphorylation, increased NO levels and improved endothelium-dependent vasorelaxation in ApoE -/- mice. High- and medium-dose TPHXR, but not low-dose TPHXR, decreased the expression of cav-1, NF-κB p50, NF-κB p65, ICAM1, VCAM-1, TNF-α, IL-6, and IL-1β in the vasculature of ApoE -/- mice. Enzyme-linked immunosorbent assay analysis indicated that high- and medium-dose TPHXR decreased the levels of TNF-α, IL-6, hs-CRP, and IL-1β. In conclusion, our findings show that TPHXR improved the endothelial function and reduced atheromatous lesions in ApoE -/- mice. This result may be due to the decreased expression of caveolin-1 and NF-κB and, hence, the attenuated inflammatory response in AS mice vasculature. TPHXR may represent a promising intervention in patients with AS.

Automatic Coronary Wall and Atherosclerotic Plaque Segmentation from 3D Coronary CT Angiography

Coronary plaque burden measured by coronary computerized tomography angiography (CCTA), independent of stenosis, is a significant independent predictor of coronary heart disease (CHD) events and mortality. Hence, it is essential to develop comprehensive CCTA plaque quantification beyond existing subjective plaque volume or stenosis scoring methods. The purpose of this study is to develop a framework for automated 3D segmentation of CCTA vessel wall and quantification of atherosclerotic plaque, independent of the amount of stenosis, along with overcoming challenges caused by poor contrast, motion artifacts, severe stenosis, and degradation of image quality. Vesselness, region growing, and two sequential level sets are employed for segmenting the inner and outer wall to prevent artifact-defective segmentation. Lumen and vessel boundaries are joined to create the coronary wall. Curved multiplanar reformation is used to straighten the segmented lumen and wall using lumen centerline. In-vivo evaluation included CCTA stenotic and non-stenotic plaques from 41 asymptomatic subjects with 122 plaques of different characteristics against the individual and consensus of expert readers. Results demonstrate that the framework segmentation performed robustly by providing a reliable working platform for accelerated, objective, and reproducible atherosclerotic plaque characterization beyond subjective assessment of stenosis; can be potentially applicable for monitoring response to therapy.

Application of a Simple Quantitative Assessment of Atherosclerotic Lesions in Freshly Isolated Aortas from Rabbits.

Rabbits are widely used for the study of atherosclerosis; however, the lack of a unified and quantitative analysis of atheroma limits data interpretation and comparisons between laboratories. In this study, we applied a simple quantitative method, referred to as the oil red O (ORO) dye-eluting method, for analysis of atherosclerotic plaques in freshly isolated aortas. It employs ORO staining of the plaques followed by elution of the dye that is subjected to quantitative measurement. Atherosclerosis was induced in rabbits by feeding a 1% (w/w) high cholesterol diet for 4 or 12weeks. Thoracic aortas were isolated and sufficiently stained by ORO. These dyes were easily and completely extracted by 100% ethanol and quantified by spectrophotometric measurement at 510nm. A series of cross-sectional slices at 100-µm intervals were counterstained by elastic van Gieson. It was found that there was a highly positive correlation between the dye concentration and the amount of plaque tissue, determined as volume of plaques (regression coefficient r2: 0.8792, p < 0.001). The color equivalence of the dye content was expressed as µg/mm2 of intimal aorta area to allow direct comparisons among aortas. The color equivalences of ORO content in rabbits fed 12weeks were almost 5.0 times higher than those fed 4weeks. Thus, this ORO dye-eluting method is useful for quantification of atherosclerotic plaques in aortas in rabbits, as well as other animal models.

A review of computational methods applied for identification and quantification of atherosclerotic plaques in images

Evaluation of the composition of atherosclerotic plaques in images is an important task to determine their pathophysiology. Visual analysis is still as the most basic and often approach to determine the morphology of the atherosclerotic plaques. In addition, computer-aided methods have also been developed for identification of features such as echogenicity, texture and surface in such plaques. In this article, a review of the most important methodologies that have been developed to identify the main components of atherosclerotic plaques in images is presented. Hence, computational algorithms that take into consideration the analysis of the plaques echogenicity, image processing techniques, clustering algorithms and supervised classification used for segmentation, i.e. identification, of the atherosclerotic plaque components in ultrasound, computerized tomography and magnetic resonance images are introduced. The main contribution of this paper is to provide a categorization of the most important studies related to the segmentation of atherosclerotic plaques and its components in images acquired by the most used imaging modalities. In addition, the effectiveness and drawbacks of each methodology as well as future researches concerning the segmentation and classification of the atherosclerotic lesions are also discussed.

Correction of lumen contrast-enhancement influence on non-calcified coronary atherosclerotic plaque quantification on CT.

Lumen contrast-enhancement influences non-calcified atherosclerotic plaque Hounsfield-unit (HU) values in computed tomography (CT). This study aimed to construct and validate an algorithm to correct for this influence. Three coronary vessel phantoms with 1, 2, and 4 mm circular hollow lumina; with normal and plaque-infested walls were scanned simultaneously in oil using a dual-source CT scanner. Scanning was repeated as the lumina were alternately filled with water and four contrast solutions (100-400 HU, at 100 HU intervals). Images were reconstructed at 0.4 mm x-y pixel size. Pixel-by-pixel comparisons of contrast-enhanced and non-contrast-enhanced images confirmed exponential declining patterns in lumen contrast-enhancement influence on wall HU-values from the lumen border (y = Ae(-λx) + c). The median difference of the inside and outside 2-pixel radius part of the contrast-enhanced coronary phantom wall to the reference (non-contrast-enhanced images) was 45 and 2 HU, respectively. Based on the lumen contrast-enhancement influence patterns, a generalized correction algorithm was formulated. Application of the generalized correction algorithm to the inside 2-pixel radius part of the wall reduced the median difference to the reference to 4 HU. In conclusion, lumen contrast-enhancement influence on the vessel wall can be defined by an exponential approximation, allowing correction of the CT density of the vessel wall closest to the lumen. With this correction, a more accurate determination of vessel wall composition can be made.

Inter-rater reliability of carotid atherosclerotic plaque quantification by 3-dimensional sonography.

Embolization from atherosclerotic carotid plaques is the most common cause of ischemic stroke; therefore, identification of high-risk plaques by sonography is important. The aim of this study was to investigate the agreement between 2 investigators in the evaluation of sonographic parameters relating to plaque stability. The following plaque parameters were assessed: echogenicity, homogeneity, surface, maximum content, and total volume. Serial 2-dimensional (2D) image sequences were obtained. Linear motion of the probe was automatically synchronized with the electrocardiogram. The edges of the plaque in each image were manually identified by the investigators. The total plaque volume was calculated after computer transformation of 2D images into a 3-dimensinoal (3D) format. Inter-rater reliability for echogenicity, homogeneity, and the surface was assessed by the weighted κ coefficient. Parametric values were tested by a paired t test. We enrolled 30 patients (22 male; mean age ± SD, 72 ± 13 years) in the study and evaluated 28 atherosclerotic plaques. Inter-rater agreement values were as follows: homogeneity, 96% (κ = 0.84; P < .001); surface, 90% (κ = 0.77; P < .001); and echogenicity, 86% (κ = 0.60; P < .001). The significance values for plaque content and volume measurement agreement were P = .311 and .312, respectively, and the correlation coefficient was 0.808. In our study, the agreement between 2 examiners in the evaluation of 2D and 3D sonographic parameters related to plaque stability was good to excellent. The sonographic measurement of plaque volume growth was the most accurate parameter; therefore, 3D sonography may be used for risk assessment of plaques in the future.

Quantitative Coronary Angiography: Back to the Past

In patients with coronary artery disease, quantitative coronary angiography (QCA) has proved to be a good method for quantification of atherosclerotic plaques since 80’ years. It is used for diagnosis and management in catheterization laboratory of a lot of patients undergoing percutaneous coronary intervention. QCA allows us to assess with dedicated computer software the impact of atherosclerosis on the lumen of the coronary arteries and to establish over time whether an intervention attenuates progression or regression of atherosclerotic disease. Currently, the use of QCA, in catheterization laboratory during percutaneous coronary intervention, is the most used method to investigate precisely the performance of coronary plaque; it, also, allows studying the efficacy of coronary intervention; nevertheless this technique has some limitations and difficulties resulting from the routine use in the evaluation of parameters. This review aims to summarize the principles and the methods used for quantitative coronary angiography with a look on the past and present describing also more recent patents and developments. Keywords: Angiography, atherosclerotic plaque, coronary angioplasty, coronary disease, coronary stenosis.

Quantification of Atherosclerotic Plaque Activity and Vascular Inflammation using [18-F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT)

Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide information about the burden of disease. However, despite multiple validation studies of CAC, and C-IMT, these modalities do not accurately assess plaque characteristics, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events. [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an important source of cellular inflammation in vessel walls. More recently, we and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy as well as longer term therapeutic lifestyle changes (16 months). The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is calculated by dividing the arterial SUV by the venous blood pool SUV. This method has shown to represent a stable, reproducible phenotype over time, has a high sensitivity for detection of vascular inflammation, and also has high inter-and intra-reader reliability. Here we present our methodology for patient preparation, image acquisition, and quantification of atherosclerotic plaque activity and vascular inflammation using SUV, TBR, and a global parameter called the metabolic volumetric product (MVP). These approaches may be applied to assess vascular inflammation in various study samples of interest in a consistent fashion as we have shown in several prior publications.

A Volumetric Method for Quantifying Atherosclerosis in Mice by Using MicroCT: Comparison to En Face

Precise quantification of atherosclerotic plaque in preclinical models of atherosclerosis requires the volumetric assessment of the lesion(s) while maintaining in situ architecture. Here we use micro-computed tomography (microCT) to detect ex vivo aortic plaque established in three dyslipidemic mouse models of atherosclerosis. All three models lack the low-density lipoprotein receptor (Ldlr−/−), each differing in plaque severity, allowing the evaluation of different plaque volumes using microCT technology. From clearly identified lesions in the thoracic aorta from each model, we were able to determine plaque volume (0.04–3.1 mm3), intimal surface area (0.5–30 mm2), and maximum plaque (intimal-medial) thickness (0.1–0.7 mm). Further, quantification of aortic volume allowed calculation of vessel occlusion by the plaque. To validate microCT for future preclinical studies, we compared microCT data to intimal surface area (by using en face methodology). Both plaque surface area and plaque volume were in excellent correlation between microCT assessment and en face surface area (r2 = 0.99, p<0.0001 and r2 = 0.95, p<0.0001, respectively). MicroCT also identified internal characteristics of the lipid core and fibrous cap, which were confirmed pathologically as Stary type III-V lesions. These data validate the use of microCT technology to provide a more exact empirical measure of ex vivo plaque volume throughout the entire intact aorta in situ for the quantification of atherosclerosis in preclinical models.