Validation of Wall Shear Stress Assessment in Non-invasive Coronary CTA versus Invasive Imaging: A Patient-Specific Computational Study.

Endothelial shear stress (ESS) identifies coronary plaques at high risk for progression and/or rupture leading to a future acute coronary syndrome. In this study an optimized methodology was developed to derive ESS, pressure drop and oscillatory shear index using computational fluid dynamics (CFD) in 3D models of coronary arteries derived from non-invasive coronary computed tomography angiography (CTA). These CTA-based ESS calculations were compared to the ESS calculations using the gold standard with fusion of invasive imaging and CTA. In 14 patients paired patient-specific CFD models based on invasive and non-invasive imaging of the left anterior descending (LAD) coronary arteries were created. Ten patients were used to optimize the methodology, and four patients to test this methodology. Time-averaged ESS (TAESS) was calculated for both coronary models applying patient-specific physiological data available at the time of imaging. For data analysis, each 3D reconstructed coronary artery was divided into 2 mm segments and each segment was subdivided into 8 arcs (45°).TAESS and other hemodynamic parameters were averaged per segment as well as per arc. Furthermore, the paired segment- and arc-averaged TAESS were categorized into patient-specific tertiles (low, medium and high). In the ten LADs, used for optimization of the methodology, we found high correlations between invasively-derived and non-invasively-derived TAESS averaged over segments (n = 263, r = 0.86) as well as arcs (n = 2104, r = 0.85, p < 0.001). The correlation was also strong in the four testing-patients with r = 0.95 (n = 117 segments, p = 0.001) and r = 0.93 (n = 936 arcs, p = 0.001).There was an overall high concordance of 78% of the three TAESS categories comparing both methodologies using the segment- and 76% for the arc-averages in the first ten patients. This concordance was lower in the four testing patients (64 and 64% in segment- and arc-averaged TAESS). Although the correlation and concordance were high for both patient groups, the absolute TAESS values averaged per segment and arc were overestimated using non-invasive vs. invasive imaging [testing patients: TAESS segment: 30.1(17.1-83.8) vs. 15.8(8.8-63.4) and TAESS arc: 29.4(16.2-74.7) vs 15.0(8.9-57.4) p < 0.001]. We showed that our methodology can accurately assess the TAESS distribution non-invasively from CTA and demonstrated a good correlation with TAESS calculated using IVUS/OCT 3D reconstructed models.

Automated Quantitative Assessment of Coronary Calcification Using Intravascular Ultrasound.

Coronary calcification represents a challenge in the treatment of coronary artery disease by stent placement. It negatively affects stent expansion and has been related to future adverse cardiac events. Intravascular ultrasound (IVUS) is known for its high sensitivity in detecting coronary calcification. At present, automated quantification of calcium as detected by IVUS is not available. For this reason, we developed and validated an optimized framework for accurate automated detection and quantification of calcified plaque in coronary atherosclerosis as seen by IVUS. Calcified lesions were detected by training a supported vector classifier per IVUS A-line on manually annotated IVUS images, followed by post-processing using regional information. We applied our framework to 35 IVUS pullbacks from each of the three commonly used IVUS systems. Cross-validation accuracy for each system was >0.9, and the testing accuracy was 0.87, 0.89 and 0.89 for the three systems. Using the detection result, we propose an IVUS calcium score, based on the fraction of calcium-positive A-lines in a pullback segment, to quantify the extent of calcified plaque. The high accuracy of the proposed classifier suggests that it may provide a robust and accurate tool to assess the presence and amount of coronary calcification and, thus, may play a role in image-guided coronary interventions.

The Effect of Spatial and Temporal Resolution of Cine Phase Contrast MRI on Wall Shear Stress and Oscillatory Shear Index Assessment.

INTRODUCTION: Wall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI (PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom. METHODS: A carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions. RESULTS: The mean PC-MRI CCA flow (2.5±0.2mL/s) agreed with the ultrasound probe measurements (2.7±0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:-17%/mm) and temporal resolution (CCA:-19%/100ms, ICA:-24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA:30/30, ICA:28/30 cases for WSS; CCA:23/30, ICA:29/30 cases for OSI). CONCLUSION: We show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution.

Carotid Plaque Morphological Classification Compared With Biomechanical Cap Stress: Implications for a Magnetic Resonance Imaging-Based Assessment.

BACKGROUND AND PURPOSE: Two approaches to target plaque vulnerability-a histopathologic classification scheme and a biomechanical analysis-were compared and the implications for noninvasive risk stratification of carotid plaques using magnetic resonance imaging were assessed. METHODS: Seventy-five histological plaque cross sections were obtained from carotid endarterectomy specimens from 34 patients (>70% stenosis) and subjected to both a Virmani histopathologic classification (thin fibrous cap atheroma with <0.2-mm cap thickness, presumed vulnerable) and a peak cap stress computation (<140 kPa: presumed stable; >300 kPa: presumed vulnerable). To demonstrate the implications for noninvasive plaque assessment, numeric simulations of a typical carotid magnetic resonance imaging protocol were performed (0.62×0.62 mm(2) in-plane acquired voxel size) and used to obtain the magnetic resonance imaging-based peak cap stress. RESULTS: Peak cap stress was generally associated with histological classification. However, only 16 of 25 plaque cross sections could be labeled as high-risk (peak cap stress>300 kPa and classified as a thin fibrous cap atheroma). Twenty-eight of 50 plaque cross sections could be labeled as low-risk (a peak cap stress<140 kPa and not a thin fibrous cap atheroma), leading to a κ=0.39. 31 plaques (41%) had a disagreement between both classifications. Because of the limited magnetic resonance imaging voxel size with regard to cap thickness, a noninvasive identification of only a group of low-risk, thick-cap plaques was reliable. CONCLUSIONS: Instead of trying to target only vulnerable plaques, a more reliable noninvasive identification of a select group of stable plaques with a thick cap and low stress might be a more fruitful approach to start reducing surgical interventions on carotid plaques.

A CT-based Medina classification in coronary bifurcations: does the lumen assessment provide sufficient information?

AIMS: To evaluate the distribution of atherosclerosis at bifurcations with computed tomography coronary angiography (CTCA) and propose a novel CT-Medina classification for bifurcation lesions. METHODS: In 26 patients (age 55 ± 10 years, 81% male) imaged with CTCA, 39 bifurcations were studied. The bifurcations analysis included the proximal main vessel, the distal main vessel and the side branch (SB). Plaque contours were manually traced on CTCA; the lumen, vessel and plaque area were measured, as well as plaque burden (%). The carina cross-sections were divided into four equal parts according to the expected wall shear stress (WSS) to assess circumferential plaque distribution. All the bifurcation lesions were classified using the Medina classification and a novel CT-Medina classification combining lumen narrowing and plaque burden ≥70%. RESULTS: Presence of severe plaque (plaque burden ≥70%) by CTCA was demonstrated in 12.8% (5/39) of the proximal segments, 15.4% (6/39) of the distal segments and 7.7% (3/39) of the SB segments. The thickest plaque was located more often in low WSS parts of the carina cross-sections, whereas the flow divider was rarely affected. Although in the majority of bifurcations plaque was present, based on the Medina classification 92% of the assessed bifurcations were identified as 0,0,0. Characterization of bifurcation lesions using the new CT-Medina classification provided additional information in seven cases (18%) compared to the Medina classification CONCLUSION: Atherosclerotic plaque is widely present in all bifurcation segments, even in the absence of coronary lumen stenosis. A CT-Medina classification combining lumen and plaque parameters is more informative than angiographic classification of bifurcation lesions and could potentially facilitate the decision-making on the treatment of these lesions.

Advanced three-dimensional quantitative coronary angiographic assessment of bifurcation lesions: methodology and phantom validation.

AIMS: Validation of new three-dimensional (3-D) bifurcation quantitative coronary angiography (QCA) software. METHODS AND RESULTS: Cardiovascular Angiography Analysis System (CAAS 5v10) allows 3-D angiographic reconstructions based on two or more 2-D projection images. Measurements for minimal lumen diameter (MLD), reference vessel diameter (RVD), percent diameter stenosis (DS) and bifurcation angle (BA) were validated against precision manufactured phantom bifurcations. Length measurements were validated against angiographic measurement catheters inserted into a plexiglas bifurcation phantom. In 3-D reconstructions based on two 2-D images, acquired at variable rotation and angulation, accuracy and precision (mean difference ± SD) of the 11-segment model for MLD, RVD and DS were 0.013±0.131 mm, -0.052±0.039 mm and -1.08±5.13%, respectively; inter-observer variability was 0.141 mm, 0.058 mm and 5.42%, respectively. Adding the antero-posterior (optimal) projection to these basic reconstructions resulted in reduced variability (0.101 mm, 0.041 mm and 3.93% for MLD, RVD and DS, p<0.01 for all) and showed a trend towards improved precision (0.109 mm, 0.031 mm and 4.26%, respectively, p>0.05 for all). In basic reconstructions, accuracy and precision for BA was -1.3±5.0°, whereas inter-observer variability was 7.5°; respective measures for length were 0.15±0.26 mm and 0.54 mm. Adding the antero-posterior projection resulted in decreased precision (0.47 mm, p<0.01) and increased variability (1.03 mm, p<0.01) for length measurements; precision (5.4°) and variability (7.9°) for BA did not change significantly (p>0.30). CONCLUSIONS: Advances in the methodology of 3-D reconstruction and quantitative analysis for bifurcation lesions translated into highly accurate, precise and reproducible measures of diameter, length and BA.

In vivo assessment of the relationship between shear stress and necrotic core in early and advanced coronary artery disease.

AIMS: Atherosclerotic plaques develop at low shear stress locations in the arterial tree. However, at a certain moment, plaques encroach into the lumen causing local wall shear stress (WSS) increase. Minimal information is available on the relationship between WSS and plaque composition. We investigated in human coronary arteries in vivo the frequency with which the necrotic core and necrotic core in contact with the lumen are located at either low or high WSS regions in early and advanced plaques. METHODS AND RESULTS: We combined a 3-D reconstruction technique of coronary arteries based on angiography and intravascular ultrasound with IVUS-virtual histology (IVUS-VH) data. With IVUS-VH the necrotic core was determined. The lumen of these 3-D reconstructions served as input for the computational fluid dynamics. Per cross-section the WSS at the regions with major necrotic core and necrotic core in contact with the lumen were compared to the median WSS in the cross-section. Ten human coronary arteries were studied. Only cross-sections with average wall thickness >0.5 mm were included in the analysis. In early plaques (plaque burden <40%), the necrotic core was most frequently located at WSS smaller than the median (61%) contrasting the advanced plaques (plaque burden >40%), being located at WSS higher than the median (60%, p<0.05 Mann-Whitney U test). Necrotic core in contact with the lumen was most often exposed to high WSS, being most pronounced in advanced disease (61%, p<0.05). CONCLUSIONS: With the advancement of disease, necrotic core is less often located at low WSS regions, but exposed to high WSS, which is probably the result of lumen narrowing. Necrotic core in contact with the lumen was most frequently exposed to high WSS.

Advances in two-dimensional quantitative coronary angiographic assessment of bifurcation lesions: improved small lumen diameter detection and automatic reference vessel diameter derivation.

AIMS: To validate a new two dimensional (2-D) bifurcation quantitative coronary angiography (QCA) software. METHODS AND RESULTS: In the latest edition of the Cardiovascular Angiography Analysis System (CAAS 5.9; Pie Medical Imaging, Maastricht, The Netherlands) video-densitometric information is dynamically integrated into the edge-detection algorithm of 11- and 6-segment models to reduce overestimation of small diameters. Furthermore, automatic reference obstruction analysis was optimised. Values of the minimal lumen diameter (MLD), reference vessel diameter (RVD), percent diameter stenosis (DS) and bifurcation angle (BA) for the different bifurcation segment models were validated against precision manufactured plexiglass phantoms. In anteroposterior views, accuracy and precision (mean difference±SD) of 11- and 6-segment models for MLD were 0.013±0.082 mm vs. 0.003±0.100 mm, for RVD -0.030±0.047 mm vs. -0.029±0.045 mm and for DS -0.48±3.66% vs. -0.11±3.97%. In smaller vessel segments (true MLD <0.7 mm), MLD overestimation was reduced. Inter-observer variability for MLD, RVD and DS for either model was ≤0.052 mm, ≤0.043 mm and ≤2.24%, respectively. Agreement between models for MLD, RVD and DS was ±0.076 mm, ±0.021 mm and ±2.53%, respectively. Accuracy and precision for BA were -2.6±3.5°, and variability was ≤1.2°. Accuracy and precision for diameter-derived parameters were slightly decreased in projections with 30° rotation; BA precision dropped to 6.2°. CONCLUSIONS: MLD quantification is improved for true MLD <0.7 mm, resulting in highly accurate and precise diameter measurements over the entire range of phantom diameters. Automatic reference obstruction analysis provides highly accurate, precise and reproducible RVD and DS measurements.

Validity and variability in visual assessment of stenosis severity in phantom bifurcation lesions: a survey in experts during the fifth meeting of the European Bifurcation Club.

OBJECTIVES: To investigate the adequacy of visual estimate regarding the percent diameter stenosis (DS) in bifurcation lesions. BACKGROUND: Quantitative coronary angiography (QCA) is more accurate and precise compared to visual estimate in assessing stenosis severity in single-vessel lesions. METHODS: Thirty-six experts in the field of bifurcation PCI visually assessed the DS in cine images of five precision manufactured phantom bifurcation lesions, experts being blinded to the true values. Expert DS estimates were compared with the true values and they were also used to define the Medina class of each individual bifurcation. Results were pooled together both for proximal main vessel (PMV), distal main vessel (DMV) and side-branch (SB) segments and for vessel segments with similar DS values. RESULTS: Individual performance was highly variable among observers; pooled values and range of accuracy and precision were 2.79% (-6.67% to 17.33%) and 8.69% (4.31-16.25%), respectively. On average, DS was underestimated in the PMV (-1.08%, P = 0.10) and overestimated in the DMV (3.86% P < 0.01) and SB segments (5.58%, P < 0.01). Variability in visual estimates was significantly larger in lesions of medium severity compared to the clearly obstructive ones (P < 0.01); the latter were consistently overestimated. Inter-observer agreement was moderate (κ = 0.55) over the entire number of estimates. However, if the segments with true DS = 0% were excluded, agreement was diminished (κ = 0.27). Inter-observer agreement in Medina class was rather low (κ = 0.21). True bifurcation lesions were misclassified as non-true ones in 14/180 estimates. CONCLUSIONS: Visual assessment by experts is more variable and less precise in the analysis of bifurcation lesions compared to bifurcation QCA software.

In vivo assessment of high-risk coronary plaques at bifurcations with combined intravascular ultrasound and optical coherence tomography.

OBJECTIVES: This study sought to evaluate the in vivo frequency and distribution of high-risk plaques (i.e., necrotic core rich) at bifurcations using a combined plaque assessment with intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT). BACKGROUND: Pathological examinations have shown that atherosclerotic plaque rich in necrotic core is prone to develop at bifurcations. High-risk plaque detection could be improved by the combined use of a technique able to detect necrotic core (IVUS-VH) and a high-resolution technique that allows the measurement of the fibrous cap thickness (OCT). METHODS: From 30 patients imaged with IVUS-VH and OCT, 103 bifurcations were selected. The main branch was analyzed at the proximal rim of the ostium of the side branch, at the in-bifurcation segment and at the distal rim of the ostium of the side branch. Plaques with more than 10% confluent necrotic core by IVUS-VH were selected and classified as fibroatheroma (FA) or thin-cap fibroatheroma (TCFA) depending on the thickness of the fibrous cap by OCT (>65 or < or =65 microm for FA and TCFA, respectively). RESULTS: Twenty-seven FA (26.2%) and 18 TCFA (17.4%) were found out of the 103 lesions studied. Overall the percentage of necrotic core decreases from proximal to distal rim (16.8% vs. 13.5% respectively, p = 0.01), whereas the cap thickness showed an inverse tendency (130 +/- 105 microm vs. 151 +/- 68 microm for proximal and distal rim, respectively, p = 0.05). The thin caps were more often located in the proximal rim (15 of 34, 44.1%), followed by the in-bifurcation segment (14 of 34, 41.2%), and were less frequent in the distal rim (5 of 34, 14.7%). CONCLUSIONS: The proximal rim of the ostium of the side branch has been identified as a region more likely to contain thin fibrous cap and a greater proportion of necrotic core.