Introduction: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular... Show moreIntroduction: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular events. A positive association between previous antiplatelet use and IPH was reported in a cross-sectional analysis. We investigated the changes in IPH over 2 years in patients who recently started versus those with continued antiplatelet use. Methods: In the Plaque at Risk (PARISK) study, symptomatic patients with <70% ipsilateral carotid stenosis underwent carotid plaque magnetic resonance imaging (MRI) at the baseline and after 2 years to determine IPH presence and volume. Participants were categorized into new users (starting antiplatelet therapy following the index event) and continued users (previous use of antiplatelet therapy before the index event). The association between previous antiplatelet therapy and the presence of IPH at baseline MRI was investigated using multivariable logistic regression analysis. The IPH volume change over a period of 2 years, defined as the difference in volume between follow-up and baseline, was investigated in each group with a Wilcoxon signed-rank test. The IPH volume change was categorized as progression, regression, or no change. Using multivariable logistic regression, we investigated the association between new antiplatelet use and (1) newly developed ipsilateral or contralateral IPH and (2) IPH volume progression. Results: A total of 108 patients underwent carotid MRI at the baseline and follow-up. At the baseline, previous antiplatelet therapy was associated with any IPH (OR = 5.6, 95% CI: 1.3–23.1; p = 0.02). Ipsilateral IPH volume did not change significantly during the 2 years in patients who continued receiving antiplatelet agents (86.4 mm3 [18.2–235.9] vs. 59.3 mm3 [11.4–260.3]; p = 0.6) nor in the new antiplatelet users (n = 31) (61.5 mm3 [0.0–166.9] vs. 27.7 mm3 [9.5–106.4]; p = 0.4). Similar results of a nonsignificant change in contralateral IPH volume during those 2 years were observed in both groups (p > 0.05). No significant associations were found between new antiplatelet use and newly developed IPH at 2 years (odds ratio [OR] = 1.0, 95% CI: 0.1–7.4) or the progression of IPH (ipsilateral: OR = 2.4, 95% CI: 0.3–19.1; contralateral: OR = 0.3, 95% CI: 0.01–8.5). Conclusion: Although the baseline association between IPH and previous antiplatelet therapy was confirmed in this larger cohort, the new onset of antiplatelet therapy after transient ischemic attack/stroke was not associated with the newly developed IPH or progression of IPH volume over the subsequent 2 years. Show less
Moerman, A.M.; Visscher, M.; Slijkhuis, N.; Gaalen, K. van; Heijs, B.; Klein, T.; ... ; Soest, G. van 2021
Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids... Show moreCarotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids, and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of >90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, whereas diacylglycerols and tri-acylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear colocalization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques. Show less
Leung, K.Y.E.; Stralen, M. van; Danilouchkine, M.G.; Burken, G. van; Geleijnse, M.L.; Reiber, J.H.C.; ... ; Bosch, J.G. 2012
Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the... Show moreRupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized geometries, in most cases measured by in-vivo MRI. The geometry is therefore not stress-free. The aim of this study is to identify the effect of neglecting the initial stress state on the plaque stress distribution. Fifty 2D histological sections (7 patients, 9 diseased coronary artery segments), perfusion fixed at 100 mmHg, were segmented and finite element models were created. The Backward Incremental method was applied to determine the initial stress state and the zero-pressure state. Peak plaque and cap stresses were compared with and without initial stress. The effect of initial stress on the peak stress was related to the minimum cap thickness, maximum necrotic core thickness, and necrotic core angle. When accounting for initial stress, the general relations between geometrical features and peak cap stress remain intact. However, on a patient-specific basis, accounting for initial stress has a different effect on the absolute cap stress for each plaque. Incorporating initial stress may therefore improve the accuracy of future stress based rupture risk analyses for atherosclerotic plaques. (C) 2011 Elsevier Ltd. All rights reserved. Show less
Leung, K.Y.E.; Stralen, M. van; Danilouchkine, M.G.; Burken, G. van; Geleijnse, M.L.; Reiber, J.H.C.; ... ; Bosch, J.G. 2011
Real-time three-dimensional (3D) ultrasound imaging has been proposed as an alternative for two-dimensional stress echocardiography for assessing myocardial dysfunction and underlying coronary... Show moreReal-time three-dimensional (3D) ultrasound imaging has been proposed as an alternative for two-dimensional stress echocardiography for assessing myocardial dysfunction and underlying coronary artery disease. Analysis of 3D stress echocardiography is no simple task and requires considerable expertise. In this paper, we propose methods for automated analysis, which may provide a more objective and accurate diagnosis. Expert knowledge is incorporated via statistical modelling of patient data. Methods for identifying anatomical views, detecting endocardial borders, and classification of wall motion are described and shown to provide favourable results. We also present software developed especially for analysis of 3D stress echocardiography in clinical practice. Interobserver agreement in wall motion scoring is better using the dedicated software (96%) than commercially available software not dedicated for this purpose (79%). The developed tools may provide useful quantitative and objective parameters to assist the clinical expert in the diagnosis of left ventricular function. Show less
Giessen, A.G. van der; Schaap, M.; Gijsen, F.J.H.; Groen, H.C.; Walsum, T. van; Mollet, N.R.; ... ; Wentzel, J.J. 2010
Wall shear stress, the force per area acting on the lumen wall due to the blood flow, is an important biomechanical parameter in the localization and progression of atherosclerosis. To calculate... Show moreWall shear stress, the force per area acting on the lumen wall due to the blood flow, is an important biomechanical parameter in the localization and progression of atherosclerosis. To calculate shear stress and relate it to atherosclerosis, a 3D description of the lumen and vessel wall is required. We present a framework to obtain the 3D reconstruction of human coronary arteries by the fusion of intravascular ultrasound (IVUS) and coronary computed tomography angiography (CT). We imaged 23 patients with IVUS and CT. The images from both modalities were registered for 35 arteries, using bifurcations as landmarks. The IVUS images together with IVUS derived lumen and wall contours were positioned on the 3D centerline, which was derived from CT. The resulting 3D lumen and wall contours were transformed to a surface for calculation of shear stress and plaque thickness. We applied variations in selection of landmarks and investigated whether these variations influenced the relation between shear stress and plaque thickness. Fusion was successfully achieved in 31 of the 35 arteries. The average length of the fused segments was 36.4 +/- 15.7 mm. The length in IVUS and CT of the fused parts correlated excellently (R-2 = 0.98). Both for a mildly diseased and a very diseased coronary artery, shear stress was calculated and related to plaque thickness. Variations in the selection of the landmarks for these two arteries did not affect the relationship between shear stress and plaque thickness. This new framework can therefore successfully be applied for shear stress analysis in human coronary arteries. Show less
