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    <title>Wentzel, J.J.</title>
    <link>http://repub.eur.nl/res/aut/508/</link>
    <description>List of Publications</description>
    <language>en</language>
    <image>
      <url>http://repub.eur.nl/static-eur/img/logo.png</url>
      <title>RePub, Erasmus University Rotterdam</title>
      <link>http://repub.eur.nl</link>
    </image>
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      <title>Transglutaminase activity regulates atherosclerotic plaque composition at locations exposed to oscillatory shear stress (Article)</title>
      <link>http://repub.eur.nl/res/pub/37404/</link>
      <pubDate>2012-10-01T00:00:00Z</pubDate>
      <description>Objective: Atherosclerosis preferentially develops at sites of disturbed blood flow. We tested the hypothesis that transglutaminase activity plays a role in plaque development at these locations. Methods and results: Exposure of endothelial cells to steady flow (7 dynes/cm2) was associated with relatively low transglutaminase activity, whereas under low oscillatory flow (1.3 ± 2.6 dynes/cm2) endothelial cells showed a &gt;4-fold higher level of transglutaminase activity. Under oscillatory flow, transglutaminase activity increased the expression of the chemokine MCP-1 (CCL2). In vivo, oscillatory flow was induced by placement of a tapered perivascular cast around the carotid artery of type 2 transglutaminase (TGM2) knockout mice and WT counterparts. After 2 days, significantly less monocytes adhered to the endothelium in TGM2 knockout mice as compared to WT. In a more chronic setting, ApoE knockout mice that were equipped with the flow-modifying cast developed lesions proximal to the cast (low shear stress), and distal to the cast (oscillatory shear stress). Inhibition of transglutaminase induced a marked reduction in macrophage and fat content in distal lesions only. In addition, lesion size was increased in this area, which was attributed to an increase in smooth muscle content. Conclusion: Oscillatory shear stress increases endothelial transglutaminase activity. In turn, transglutaminase activity affects the expression of MCP-1 in vitro and monocyte recruitment in vivo. In a mouse model of atherosclerosis, transglutaminase activity has a major effect on plaque composition under oscillatory shear stress. </description>
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      <title>Initial stress in biomechanical models of atherosclerotic plaques (Article)</title>
      <link>http://repub.eur.nl/res/pub/31104/</link>
      <pubDate>2011-09-02T00:00:00Z</pubDate>
      <description>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 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. </description>
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      <title>Two-dimensional quantitative coronary angiographic models for bifurcation segmental analysis: In vitro validation of CAAS against precision manufactured plexiglas phantoms (Article)</title>
      <link>http://repub.eur.nl/res/pub/34506/</link>
      <pubDate>2011-05-01T00:00:00Z</pubDate>
      <description>Background: Quantitative coronary angiography (QCA) analysis for bifurcation lesions needs to be standardized. Objectives: In vitro validation of two models for bifurcation QCA segmental analysis. Methods: In the latest edition of the Cardiovascular angiography analysis system (CAAS 5v8, Pie Medical Imaging, Maastricht, The Netherlands) a 6-segment model for two-dimensional coronary bifurcation analysis was implemented next to the currently available 11-segment model. Both models were validated against 6 precision manufactured plexiglas phantoms, each of them mimicking a vessel with three successive bifurcation lesions with variable anatomy and Medina class. The phantoms were filled with 100% contrast agent and imaged with a biplane gantry. Images acquired in antero-posterior (AP) direction by either C-arm and at 30° right and left anterior oblique angulation were analyzed by two independent analysts, blinded to the actual dimensions. Manual correction of the contours was not allowed. Measurements for minimal lumen diameter (MLD), reference vessel diameter (RVD), percent diameter stenosis (DS) and bifurcation angle (BA) were compared with the true phantom dimensions. Results: In AP views the accuracy and precision (mean difference ± SD) of 11- and 6-segment model for MLD, RVD, and DS were 0.065 ± 0.128 mm vs. 0.058 ± 0.142 mm, -0.021 ± 0.032 mm vs. -0.022 ± 0.030 mm, and -2.45% ± 5.07% vs. -2.28% ± 5.29%, respectively. Phantom MLD values 0.7 mm were systematically overestimated; if excluded, MLD accuracy and precision became 0.015 A;circ± 0.106 mm and 0.004 ± 0.125 mm for the 11- and 6-segment model, respectively. Accuracy and precision for BA were -2.2° ± 3.3°. Interobserver variability for MLD, RVD, DS, and BA for either model was &amp;0.049 mm, a;circ0.056 mm, &amp;2.77%, and 1.6°, respectively. Agreement between models for MLD, RVD, and DS was A;circ±0.079 mm, ±0.011 mm, and ±2.07%. Accuracy and precision for diameter-derived parameters were slightly decreased in angulated projections; precision for BA measurements dropped to 6.1°. Conclusions: The results of both models are highly reproducible and for phantom MLD values &gt;0.7mm in excellent agreement with the true dimensions. </description>
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      <title>Novel bifurcation phantoms for validation of quantitative coronary angiography algorithms (Article)</title>
      <link>http://repub.eur.nl/res/pub/34510/</link>
      <pubDate>2011-05-01T00:00:00Z</pubDate>
      <description>Background: Validation is lacking for two- and three-dimensional (2D and 3D) bifurcation quantitative coronary angiography (QCA) algorithms. Methods: Six plexiglas phantoms were designed, each of them mimicking a coronary vessel with three successive bifurcations lesions, wherein at least one vessel segment had a percent diameter stenosis (DS) of ≥60%. The five most frequently occurring Medina classes (1,1,1), (1,1,0), (0,1,0), (0,1,1), and (1,0,0) were used in the design. Diameters of the daughter vessels in every bifurcation were dictated by the scaling law of Finet. Lesions were cosinus-shaped in longitudinal view and circular-shaped in cross-sectional view. At the level of the carina, lesions were becoming eccentric, favoring "plaque" at the outer bifurcation walls. Adjacent bifurcation lesions were kept distant by nontapering, stenosis-free segments of ≥10 mm length. The direction of the side branch relative to the main vessel was based on relevant literature. The phantoms were precision manufactured using computer-aided design and machining techniques. Because of the high drilling accuracy (within 10 μm), the 3D luminal surface description of the phantom could be used to determine the true lumen dimensions and bifurcation angle (BA) values of the final geometry. Results: Our series of bifurcation phantoms comprised 33 narrowed and 21 stenosis-free vessel segments with a mean true minimal lumen diameter (MLD) value of 0.98 ± 0.40 mm (range, 0.53-1.96 mm) and 2.29 ± 0.74 mm (range, 1.40-4.00 mm), respectively. Overall, the mean true values for MLD, reference diameter, and DS were 1.49 ± 0.85 mm, 2.70 ± 0.71 mm, and 40.9% ± 34.2%. The mean true values for the proximal and the distal BA were 123.6° ± 19.0° and 69.6° ± 19.9°, respectively. Conclusions: Six plexiglas phantoms containing a total of 18 bifurcations lesions with variable anatomy and Medina class were designed and precision manufactured to facilitate the validation of bifurcation QCA algorithms. </description>
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      <title>Effects of intima stiffness and plaque morphology on peak cap stress (Article)</title>
      <link>http://repub.eur.nl/res/pub/25503/</link>
      <pubDate>2011-04-11T00:00:00Z</pubDate>
      <description>Background: Rupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress.Methods: Models with idealized geometries based on histology images of human coronary arteries were generated by varying geometric plaque features. The constructed multi-layer models contained adventitia, media, intima, and necrotic core sections. For adventitia and media layers, anisotropic hyperelastic material models were used. For necrotic core and intima sections, isotropic hyperelastic material models were employed. Three different intima stiffness values were used to cover the wide range reported in literature. According to the intima stiffness, the models were classified as stiff, intermediate and soft intima models. Finite element method was used to compute peak cap stress.Results: The intima stiffness was an essential determinant of cap stresses. The computed peak cap stresses for the soft intima models were much lower than for stiff and intermediate intima models. Intima stiffness also affected the influence of morphological parameters on cap stresses. For the stiff and intermediate intima models, the cap thickness and necrotic core thickness were the most important determinants of cap stresses. The peak cap stress increased three-fold when the cap thickness was reduced from 0.25 mm to 0.05 mm for both stiff and intermediate intima models. Doubling the thickness of the necrotic core elevated the peak cap stress by 60% for the stiff intima models and by 90% for the intermediate intima models. Two-fold increase in the intima thickness behind the necrotic core reduced the peak cap stress by approximately 25% for both intima models. For the soft intima models, cap thickness was less critical and changed the peak cap stress by 55%. However, the necrotic core thickness was more influential and changed the peak cap stress by 100%. The necrotic core angle emerged as a critical determinant of cap stresses where a larger angle lowered the cap stresses. Contrary to the stiff and intermediate intima models, a thicker intima behind the necrotic core increased the peak cap stress by approximately 25% for the soft intima models. Adventitia thickness and local media regression had limited effects for all three intima models.Conclusions: For the stiff and intermediate intima models, the cap thickness was the most important morphological risk factor. However for soft intima models, the necrotic core thickness and necrotic core angle had a bigger impact on the peak cap stress. We therefore need to enhance our knowledge of intima material properties if we want to derive critical morphological plaque features for risk evaluation. </description>
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      <title>The influence of boundary conditions on wall shear stress distribution in patients specific coronary trees (Article)</title>
      <link>http://repub.eur.nl/res/pub/33468/</link>
      <pubDate>2011-04-07T00:00:00Z</pubDate>
      <description>Patient specific geometrical data on human coronary arteries can be reliably obtained multislice computer tomography (MSCT) imaging. MSCT cannot provide hemodynamic variables, and the outflow through the side branches must be estimated. The impact of two different models to determine flow through the side branches on the wall shear stress (WSS) distribution in patient specific geometries is evaluated. Murray's law predicts that the flow ratio through the side branches scales with the ratio of the diameter of the side branches to the third power. The empirical model is based on flow measurements performed by Doriot et al. (2000) in angiographically normal coronary arteries. The fit based on these measurements showed that the flow ratio through the side branches can best be described with a power of 2.27. The experimental data imply that Murray's law underestimates the flow through the side branches. We applied the two models to study the WSS distribution in 6 coronary artery trees. Under steady flow conditions, the average WSS between the side branches differed significantly for the two models: the average WSS was 8% higher for Murray's law and the relative difference ranged from -5% to +27%. These differences scale with the difference in flow rate. Near the bifurcations, the differences in WSS were more pronounced: the size of the low WSS regions was significantly larger when applying the empirical model (13%), ranging from -12% to +68%. Predicting outflow based on Murray's law underestimates the flow through the side branches. Especially near side branches, the regions where atherosclerotic plaques preferentially develop, the differences are significant and application of Murray's law underestimates the size of the low WSS region. </description>
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      <title>Reproducibility, accuracy, and predictors of accuracy for the detection of coronary atherosclerotic plaque composition by computed tomography: An ex vivo comparison to intravascular ultrasound (Article)</title>
      <link>http://repub.eur.nl/res/pub/27284/</link>
      <pubDate>2010-11-01T00:00:00Z</pubDate>
      <description>Purpose: To determine the reproducibility, accuracy, and predictors of accuracy of computed tomography (CT) angiography to detect and characterize coronary atherosclerotic plaque as compared with intravascular ultrasound. Methods: Ten ex vivo human coronary arteries were imaged in a moving phantom by dual-source CT (collimation: 0.6 mm, reconstructed slice thickness: 0.4 mm) and intravascular ultrasound (IVUS). Coregistered cross-sections were assessed at 0.4 mm intervals for the presence and composition of atherosclerotic plaque (noncalcified, mixed, and calcified) on CT and IVUS by independent readers to determine reader agreement and diagnostic accuracy. Quantitative measurements of lumen and plaque area, plaque eccentricity, and intimal thickness on IVUS were used to determine predictors for the detection of noncalcified plaque by CT. Results: Within 1002 coregistered cross-sections, the interobserver agreement to detect plaque on CT was K = 0.48, K = 0.42, and K = 1.00 for noncalcified, mixed, and calcified plaque; respectively. The sensitivity and specificity of CT was 57% out of 84% for noncalcified, 32% of 92% for mixed, and 56% of 93% for calcified plaque when compared with IVUS; respectively. Misclassification occurred in 68% of mixed and 43% of noncalcified plaques. The odds of detecting noncalcified plaque in CT independently increased by 56% (95% CI: 47%-77%, P &lt; 0.0001) with every 0.1 mm increase in maximum intimal thickness as measured by IVUS. Detection rate for noncalcified plaques was poor for plaques &lt;1 mm (36%) but excellent for plaques &gt;1 mm maximal intimal thickness (90%). Conclusion: Reader agreement and diagnostic accuracy for the detection of coronary atherosclerotic plaque vary with plaque composition. Intimal thickness independently predicts detection of noncalcified plaque by CT with excellent sensitivity for &gt;1 mm thick plaques. Copyright </description>
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      <title>In vivo 3D distribution of lipid-core plaque in human coronary artery as assessed by fusion of near infrared spectroscopy-intravascular ultrasound and multislice computed tomography scan (Article)</title>
      <link>http://repub.eur.nl/res/pub/32984/</link>
      <pubDate>2010-11-01T00:00:00Z</pubDate>
      <description></description>
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      <title>3D fusion of intravascular ultrasound and coronary computed tomography for in-vivo wall shear stress analysis: A feasibility study (Article)</title>
      <link>http://repub.eur.nl/res/pub/28595/</link>
      <pubDate>2010-10-01T00:00:00Z</pubDate>
      <description>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 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 (R2= 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. </description>
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      <title>MRI-based quantification of outflow boundary conditions for computational fluid dynamics of stenosed human carotid arteries (Article)</title>
      <link>http://repub.eur.nl/res/pub/21089/</link>
      <pubDate>2010-08-01T00:00:00Z</pubDate>
      <description>Accurate assessment of wall shear stress (WSS) is vital for studies on the pathogenesis of atherosclerosis. WSS distributions can be obtained by computational fluid dynamics (CFD) using patient-specific geometries and flow measurements. If patient-specific flow measurements are unavailable, in- and outflow have to be estimated, for instance by using Murray's Law. It is currently unknown to what extent this law holds for carotid bifurcations, especially in cases where stenoses are involved. We performed flow measurements in the carotid bifurcation using phase-contrast MRI in patients with varying degrees of stenosis. An empirical relation between outflow and degree of area stenosis was determined and the outflow measurements were compared to estimations based on Murray's Law. Furthermore, the influence of outflow conditions on the WSS distribution was studied. For bifurcations with an area stenosis smaller than 65%, the outflow ratio of the internal carotid artery (ICA) to the common carotid artery (CCA) was 0.62±0.12 while the outflow ratio of the external carotid artery (ECA) was 0.35±0.13. If the area stenosis was larger than 65%, the flow to the ICA decreased linearly to zero at 100% area stenosis. The empirical relation fitted the flow data well (R2=0.69), whereas Murray's Law overestimated the flow to the ICA substantially for larger stenosis, resulting in an overestimation of the WSS. If patient-specific flow measurements of the carotid bifurcation are unavailable, estimation of the outflow ratio by the presented empirical relation will result in a good approximation of calculated WSS using CFD.</description>
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      <title>Three-dimensional registration of histology of human atherosclerotic carotid plaques to in-vivo imaging (Article)</title>
      <link>http://repub.eur.nl/res/pub/27303/</link>
      <pubDate>2010-08-01T00:00:00Z</pubDate>
      <description>An accurate spatial relationship between 3D in-vivo carotid plaque and lumen imaging and histological cross sections is required to study the relationship between biomechanical parameters and atherosclerotic plaque components. We present and evaluate a fully three-dimensional approach for this registration problem, which accounts for deformations that occur during the processing of the specimens. By using additional imaging steps during tissue processing and semi-automated non-linear registration techniques, a 3D-reconstruction of the histology is obtained.The methodology was evaluated on five specimens obtained from patients, operated for severe atherosclerosis in the carotid bifurcation. In more than 80% of the histology slices, the quality of the semi-automated registration with computed tomography angiography (CTA) was equal to or better than the manual registration. The inter-observer variability was between one and two in-vivo CT voxels and was equal to the manual inter-observer variability. Our technique showed that the angles between the normals of the registered histology slices and the in-vivo CTA scan direction ranged 6-56°, indicating that proper 3D-registration is crucial for establishing a correct spatial relation with in-vivo imaging modalities. This new 3D-reconstruction technique of atherosclerotic plaque tissue opens new avenues in the field of biomechanics as well as in the field of image processing, where it can be used for validation purposes of segmentation algorithms. </description>
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      <title>Small coronary calcifications are not detectable by 64-slice contrast enhanced computed tomography (Article)</title>
      <link>http://repub.eur.nl/res/pub/20067/</link>
      <pubDate>2010-01-01T00:00:00Z</pubDate>
      <description>Recently, small calcifications have been associated with unstable plaques. Plaque calcifications are both in intravascular ultrasound (IVUS) and multi-slice computed tomography (MSCT) easily recognized. However, smaller calcifications might be missed on MSCT due to its lower resolution. Because it is unknown to which extent calcifications can be detected with MSCT, we compared calcification detection on contrast enhanced MSCT with IVUS. The coronary arteries of patients with myocardial infarction or unstable angina were imaged by 64-slice MSCT angiography and IVUS. The IVUS and MSCT images were registered and the arteries were inspected on the presence of calcifications on both modalities independently. We measured the length and the maximum circumferential angle of each calcification on IVUS. In 31 arteries, we found 99 calcifications on IVUS, of which only 47 were also detected on MSCT. The calcifications missed on MSCT (n = 52) were significantly smaller in angle (27° ± 16° vs. 59° ± 31°) and length (1.4 ± 0.8 vs. 3.7 ± 2.2 mm) than those detected on MSCT. Calcifications could only be detected reliably on MSCT if they were larger than 2.1 mm in length or 36° in angle. Half of the calcifications seen on the IVUS images cannot be detected on contrast enhanced 64-slice MSCT angiography images because of their size. The limited resolution of MSCT is the main reason for missing small calcifications.</description>
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      <title>Coronary lumen segmentation using graph cuts and robust kernel regression (In Book)</title>
      <link>http://repub.eur.nl/res/pub/17397/</link>
      <pubDate>2009-09-21T00:00:00Z</pubDate>
      <description>This paper presents a novel method for segmenting the coronary lumen in CTA data. The method is based on graph cuts, with edge-weights depending on the intensity of the centerline, and robust kernel regression. A quantitative evaluation in 28 coronary arteries from 12 patients is performed by comparing the semi-automatic segmentations to manual annotations. This evaluation showed that the method was able to segment the coronary arteries with high accuracy, compared to manually annotated segmentations, which is reflected in a Dice coefficient of 0.85 and average symmetric surface distance of 0.22 mm.</description>
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      <title>Atherosclerotic plaque surface morphology in the carotid bifurcation assessed with multidetector computed tomography angiography (Article)</title>
      <link>http://repub.eur.nl/res/pub/16434/</link>
      <pubDate>2009-04-01T00:00:00Z</pubDate>
      <description>Background and Purpose - Complicated (irregular or ulcerated) carotid plaques have proven to be independent predictors of stroke. We analyzed the frequency and location of plaque irregularities in a large cohort of patients with ischemic cerebrovascular disease and the relation with severity of stenosis, cardiovascular risk factors, and symptomatology. Methods - Multidetector CT angiography images from 406 patients were evaluated. Plaque surface morphology was classified as smooth, irregular, or ulcerated. The location of the ulceration was defined as proximal or distal to the point of maximum stenosis. Results - Atherosclerotic plaques with an open lumen were present in 448 carotid arteries; these plaques were classified as: smooth, 276 (62%); irregular, 99 (22%); and ulcerated, 73 (16%). Sixty-two (69%) of the ulcerations were located proximal to the point of maximum luminal stenosis. Complicated plaques were significantly (P&lt;0.001) more common in carotid arteries with stenosis &gt;30% than in those with stenosis &lt;30%. There is an association between complicated plaques and hypercholesterolemia (OR, 3.0) and a trend toward an association with smoking (OR, 1.9). Complicated plaques are more often present in the symptomatic carotid artery than in the contralateral asymptomatic carotid artery; however, this is fully attributed to a significantly higher degree of stenosis in the symptomatic arteries. Conclusions - Multidetector CT angiography allows the classification of atherosclerotic carotid plaque surface. Complicated plaques are frequent in atherosclerotic carotid disease, especially with higher stenosis degree. Ulcerations are mostly located in the proximal part of the atherosclerotic plaque. Hypercholesterolemia and smoking are related with the presence of complicated plaques.</description>
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      <title>In vivo validation of CAAS QCA-3D coronary reconstruction using fusion of angiography and intravascular ultrasound (ANGUS) (Article)</title>
      <link>http://repub.eur.nl/res/pub/24077/</link>
      <pubDate>2009-04-01T00:00:00Z</pubDate>
      <description>Objectives: The CAAS QCA-3D system (Pie Medical Imaging BV, the Netherlands) was validated against 3D reconstructions based on fusion of angiography and intravascular ultrasound (ANGUS), allowing slice by slice validation of the lumen areas and 3D geometric values. Background: Accurate online 3D reconstruction of human coronary arteries is of outmost importance during clinical practice in the catheterization laboratory. The CAAS QCA-3D system provides technology to 3D reconstruct human coronary arteries based on two or more angiographic images, but was not validated in realistic arteries before. Methods: Ten patients were imaged using biplane angiography and an ECG gated (TomTec) intravascular ultrasound (IVUS) pullback (stepsize 0.5 mm, Boston Scientific). The coronary arteries were 3D reconstructed based on (a) fusion of biplane angiography and IVUS (ANGUS) and (b) CAAS QCA-3D using the biplane angiography images. For both systems the length, the curvature and the lumen areas at 0.5 mm spacing were calculated and compared. Results: Bland-Altman analysis indicated that the CAAS QCA-3D system underestimated the lumen areas systematically by 0.45 ± 1.49 mm2. The segment length was slightly underestimated by the CAAS QCA-3D system (62.1 ± 11.3 vs. 63.2 ± 11.4 mm; P &lt; 0.05), while the curvature of the analyzed segments were not statistically different. Conclusions: The CAAS QCA-3D system allows 3D reconstruction of human coronary arteries based on biplane angiography. Validation against the ANGUS system showed that both the 3D geometry and lumen areas are highly correlated which makes the CAAS QCA-3D system a promising tool for applications in the catheterization laboratory and opens possibilities for computational fluid dynamics. </description>
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      <title>In Vivo Assessment of High-Risk Coronary Plaques at Bifurcations With Combined Intravascular Ultrasound and Optical Coherence Tomography (Article)</title>
      <link>http://repub.eur.nl/res/pub/24417/</link>
      <pubDate>2009-04-01T00:00:00Z</pubDate>
      <description>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 (&gt;65 or ≤65 μm 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 μm vs. 151 ± 68 μm 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. </description>
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      <title>Coronary lumen segmentation using graph cuts and robust kernel regression. (Article)</title>
      <link>http://repub.eur.nl/res/pub/17381/</link>
      <pubDate>2009-01-01T00:00:00Z</pubDate>
      <description>This paper presents a novel method for segmenting the coronary lumen in CTA data. The method is based on graph cuts, with edge-weights depending on the intensity of the centerline, and robust kernel regression. A quantitative evaluation in 28 coronary arteries from 12 patients is performed by comparing the semi-automatic segmentations to manual annotations. This evaluation showed that the method was able to segment the coronary arteries with high accuracy, compared to manually annotated segmentations, which is reflected in a Dice coefficient of 0.85 and average symmetric surface distance of 0.22 mm.</description>
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      <title>Strain distribution over plaques in human coronary arteries relates to shear stress (Article)</title>
      <link>http://repub.eur.nl/res/pub/29611/</link>
      <pubDate>2008-10-01T00:00:00Z</pubDate>
      <description>Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into four regions: upstream, throat, shoulder, and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat, and downstream region was 2.55 ± 0.89, 2.07 ± 0.98, 2.32 ± 1.11, and 0.67 ± 0.35 Pa, respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23 ± 0.08% vs. 0.48 ± 0.15%, 0.43 ± 0.17%, and 0.47 ± 0.12%, for the upstream, shoulder, and throat regions, respectively). Pooling all regions, dividing shear stress per plaque into tertiles, and computing average strain showed a positive correlation; for low, medium, and high shear stress, strain was 0.23 ± 0.10%, 0.40 ± 0.15%, and 0.60 ± 0.18%, respectively. Low strain colocalizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with the highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture. Copyright </description>
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      <title>Simulation of stent deployment in a realistic human coronary artery (Article)</title>
      <link>http://repub.eur.nl/res/pub/30301/</link>
      <pubDate>2008-08-06T00:00:00Z</pubDate>
      <description>Background: The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis. Methods: 3D reconstruction of a mildly stenosed coronary artery was carried out based on a combination of biplane angiography and intravascular ultrasound. Finite element method computations were performed to simulate the deployment of a stent inside the reconstructed coronary artery model at inflation pressure of 1.0 MPa. Strut thickness of the stent was varied to investigate stresses in the stent and the vessel wall. Results: Deformed configurations, pressure-lumen area relationship and stress distribution in the arterial wall and stent struts were studied. The simulations show how the stent pushes the arterial wall towards the outside allowing the expansion of the occluded artery. Higher stresses in the arterial wall are present behind the stent struts and in regions where the arterial wall was thin. Values of 200 MPa for the peak stresses in the stent strut were detected near the connecting parts between the stent struts, and they were only just below the fatigue stress. Decreasing strut thickness might reduce arterial damage without increasing stresses in the struts significantly. Conclusion: The method presented in this paper can be used to predict stresses in the stent struts and the vessel wall, and thus evaluate whether a specific stent design is optimal for a specific patient. </description>
    </item> <item>
      <title>Rapamycin modulates the eNOS vs. shear stress relationship (Article)</title>
      <link>http://repub.eur.nl/res/pub/28957/</link>
      <pubDate>2008-04-01T00:00:00Z</pubDate>
      <description>Aims: Studies in animals and patients indicate that rapamycin affects vasodilatation differently in outer and inner curvatures of blood vessels. We evaluated in this study whether rapamycin affects endothelial nitric oxide synthase (eNOS) responsiveness to shear stress under normo- and hypercholesteraemic conditions to explain these findings. Methods and results: Shear stress levels were varied over a large range of values in carotid arteries of transgenic mice expressing human eNOS fused to enhanced green fluorescence protein. The mice were divided into control, low-dose rapamycin (3 μg/kg/day), and high-dose rapamycin (3 mg/kg/day) groups and into normocholesteraemic and hypercholesteraemic (ApoE-/- on high cholesterol diet for 3-4 weeks) groups. The effect of rapamycin treatment on eNOS was evaluated by quantification of eNOS expression and of intracellular protein levels by en face confocal microscopy. A sigmoid curve fit was used to described these data. The efficacy of treatment was confirmed by measurement of rapamycin serum levels (2.0 ± 0.5 ng/mL), and of p27kip1expression in vascular tissue (increased by 2.4 ± 0.5-fold). In control carotid arteries, eNOS expression increased by 1.8 ± 0.3-fold in response to rapamycin. In the treated vessels, rapamycin reduced maximal eNOS expression at high shear stress levels (&gt;5 Pa) in a dose-dependent way and shifted the sigmoid curve to the right. Hypercholesteraemia had a tendency to increase the leftward shift and the reduction in maximal eNOS expression (P = 0.07). Conclusion: Rapamycin is associated with high eNOS in low shear regions, i.e. in atherogenic regions, protecting these regions against atherosclerosis, and is associated with a reduction of eNOS at high shear stress affecting vasomotion in these regions. </description>
    </item> <item>
      <title>Large variations in absolute wall shear stress levels within one species and between species (Article)</title>
      <link>http://repub.eur.nl/res/pub/35054/</link>
      <pubDate>2007-12-01T00:00:00Z</pubDate>
      <description>Wall shear stress (WSS), the frictional force between blood and endothelium, is an important determinant of vascular function. It is generally assumed that WSS remains constant at a reference value of 15 dyn/cm2. In a study of small rodents, we realized that this assumption could not be valid. This review presents an overview of recent studies in large and small animals where shear stress was measured, derived from velocity measurements or otherwise, in large vessels. The data show that large variations exist within a single species (human: variation of 2-16 N/m2). Moreover, when we compared different species at the same location within the arterial tree, an inverse relationship between animal size and wall shear stress was noted. When we related WSS to diameter, a unique relationship was derived for all species studied. This relationship could not be described by the well-known r3law of Murray, but by the r2law introduced by Zamir et al. in 1972. In summary, by comparing data from the literature, we have shown that: (i) the assumption of a physiological WSS level of ∼15 dyn/cm2for all straight vessels in the arterial tree is incorrect; (ii) WSS is not constant throughout the vascular tree; (iii) WSS varies between species; (iv) WSS is inversely related to the vessel diameter. These data support an "r2law" rather than Murray's r3law for the larger vessels in the arterial tree. </description>
    </item> <item>
      <title>Plaque rupture in the carotid artery is localized at the high shear stress region: A case report (Article)</title>
      <link>http://repub.eur.nl/res/pub/35299/</link>
      <pubDate>2007-08-01T00:00:00Z</pubDate>
      <description>BACKGROUND AND PURPOSE - Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS. SUMMARY OF CASE - We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location. CONCLUSIONS - In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events. </description>
    </item> <item>
      <title>A new imaging technique to study 3-D plaque and shear stress distribution in human coronary artery bifurcations in vivo (Article)</title>
      <link>http://repub.eur.nl/res/pub/35308/</link>
      <pubDate>2007-07-26T00:00:00Z</pubDate>
      <description>Objective: Bifurcations of coronary arteries are predilection sites for atherosclerosis and expansive remodeling, the latter being associated with plaque vulnerability. Both are related to blood flow-induced shear stress (SS). We present a new approach to generate 3-D reconstructions of coronary artery bifurcations in vivo and investigate the relationship between SS, wall thickness (WT) and remodeling. Methods: The patient specific 3-D reconstruction of the main branch of the bifurcation was obtained by combining intravascular ultrasound and biplane angiography, and the 3-D lumen of the side branch was based on biplane angiography only. The two data sets were fused and computational methods were applied to determine the SS distribution, using patient derived flow and viscosity data. The intravascular ultrasound data allowed us to measure local WT and remodeling in the main branch. Results: The lumen reconstruction procedure was successful and it was shown that the impact of the side branch on SS distribution in the main branch diminished within 3 mm. Distal to the bifurcation, two continuous regions in the main branch were identified. In the proximal region, we observed lumen preservation, and expansive remodeling. Although a plaque was observed in the low SS region at the non-divider wall, no relationship between SS and WT was found. In the distal region, we observed lumen narrowing and a significant positive relationship between SS and WT. Conclusions: A new imaging technique was applied to generate a 3-D reconstruction of a human coronary artery bifurcation in vivo. The observed relationship between SS, WT and remodeling in this specific patient illustrates the spatial heterogeneity of the atherosclerosis in the vicinity of arterial bifurcations. </description>
    </item> <item>
      <title>Influence of catheter design on lumen wall temperature distribution in intracoronary thermography (Article)</title>
      <link>http://repub.eur.nl/res/pub/35667/</link>
      <pubDate>2007-01-01T00:00:00Z</pubDate>
      <description>Intracoronary thermography is a currently used vulnerable plaque detection method. We studied how catheter design and catheter location influence the temperature readings, and thus its capacity to detect vulnerable plaques. Finite element calculations were performed on geometries representing the coronary artery, the vulnerable plaque and the catheter. Catheter material, diameter and location with respect to the plaque were varied. Both flow and no-flow situations were studied. Maximal lumen wall temperature difference without a catheter (ΔT=0.12 °C, flow=75 cm3min-1) was considered the reference. Presence of a 1.0 mm nitinol catheter right under the plaque increased ΔT to 0.14 °C, whereas a 1.0 mm polyurethane catheter increased ΔT to 0.51 °C. The location at which a thermosensitive element should be placed for most optimal temperature readings during a pullback was shown to lie at the catheter edge for the nitinol catheter and at 1.1 mm from the catheter edge for the polyurethane catheter. Temperature readings decreased to background temperature when the catheter was in close proximity but not overlapping the plaque. ΔT decreased approximately by 70% when a gap of 0.2 mm existed between the catheter and the lumen wall. Occlusion of blood flow increased ΔT values in all cases, but most pronounced for nitinol catheters. A polyurethane catheter increased the temperature readings, since its heat conductivity is lower than that of blood, which makes it a very good choice for heat source detection. Catheter design can contribute to enhanced temperature readings and thus can enable more optimal vulnerable plaque detection. </description>
    </item> <item>
      <title>A biplane angiographic study on cardiac motion of coronary artery stents: options to minimize the target volume for high-precision external beam radiotherapy of coronary artery in-stent restenosis. (Article)</title>
      <link>http://repub.eur.nl/res/pub/4695/</link>
      <pubDate>2004-01-01T00:00:00Z</pubDate>
      <description>PURPOSE: High-precision external beam radiotherapy (EBRT) has been suggested as a potential alternative to endovascular brachytherapy for the treatment of coronary artery in-stent restenosis. The purpose of our study was to investigate and compare different options to define a smallest feasible target volume. METHODS AND MATERIALS: The cardiac motion of 17 coronary artery stents in 17 patients was studied by use of biplane conventional angiography, recorded during breath-hold. Each stent was reconstructed in three dimensions by use of biplane sets of frames covering an entire cardiac cycle. The volume traversed by the stent during the entire or part of the cardiac cycle was determined. Four options to define the stent-traversed volume (STV) as a target for high-precision EBRT were investigated. RESULTS: The mean STV during the entire cardiac cycle was 3.5 cm3; the STV represented less than 1% of the heart volume in all patients. The STV during the diastolic and systolic phase resulted in a mean reduction of 26.6% and 29.1%, respectively, compared with the STV during the entire cardiac cycle. The smallest STV, measured during a 160-ms interval within the cardiac cycle, resulted in a mean maximal reduction of 75.9% compared with the STV during the entire cardiac cycle. CONCLUSIONS: The STV during the entire cardiac cycle represents a small potential target volume for high-precision EBRT. A significant reduction of this target volume is possible in case of definition during a selected interval within the cardiac cycle.</description>
    </item> <item>
      <title>Usefulness of shear stress pattern in predicting neointima distribution in sirolimus-eluting stents in coronary arteries. (Article)</title>
      <link>http://repub.eur.nl/res/pub/4699/</link>
      <pubDate>2003-12-01T00:00:00Z</pubDate>
      <description>The true 3-dimensional neointimal thickness distribution in sirolimus-eluting stents was investigated in relation to the shear stress distribution, which was obtained from computational fluid dynamics calculations. Small pits were observed between the stent struts in all patients, and a significant inverse relation between neointimal thickness and shear stress was found, indicating that deeper pits were present in the outside curve of the stented segments.</description>
    </item> <item>
      <title>Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling. (Article)</title>
      <link>http://repub.eur.nl/res/pub/13172/</link>
      <pubDate>2003-07-08T00:00:00Z</pubDate>
      <description>BACKGROUND: Atherosclerosis preferentially develops at average low shear stress (SS) locations. SS-related signaling maintains lumen dimensions by inducing outward arterial remodeling. Prolonged plaque accumulation at low SS predilection locations explains an inverse relation between wall thickness (WT) and SS. No data exist on WT-SS relations when lumen narrowing and loss of compensatory remodeling commence. METHODS AND RESULTS: In 14 patients, an angiographically normal artery (stenosis &lt;50%) was investigated with ANGiography and ivUS (ANGUS) to provide 3D lumen and wall geometry. Selection of segments &gt;5 mm in length, in between side branches, yielded 25 segments in 12 patients. SS at the wall was calculated by computational fluid dynamics. WT smaller than 0.2*lumen diameter was defined as normal. Largest arc of normal WT defined reference cross sections. Lumen area relative to the reference cross sections defined area stenosis (AS). Average segmental AS smaller or greater than 10% defined preserved or narrowed lumen, respectively. Total vessel area relative to the reference defined vascular remodeling (VR). For the preserved lumens (n=11, AS=1.7+/-5.6%, P=NS), axially averaged WT and SS were inversely related (slope, -0.46+/-0.55 mm/Pa, P&lt;0.05) and VR was positive (7+/-9%, P&lt;0.05). Narrowed segments (n=13, 1 excluded, AS=18+/-6%, P&lt;0.05) showed no relation between WT and SS or vascular remodeling. CONCLUSIONS: In patient coronary arteries, the often-reported inverse WT-SS relationship appears restricted to lumen preservation and positive vascular remodeling. Its disappearance with lumen narrowing suggests a growing importance of non-SS-related plaque progression.</description>
    </item> <item>
      <title>Augmentation of wall shear stress inhibits neointimal hyperplasia after stent implantation: inhibition through reduction of inflammation? (Article)</title>
      <link>http://repub.eur.nl/res/pub/13158/</link>
      <pubDate>2003-01-01T00:00:00Z</pubDate>
      <description>BACKGROUND: Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent. METHODS AND RESULTS: In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (S+ARED), outside the ARED (S[minus]ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m2 in the S+ARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) lower mean late luminal loss by quantitative angiography ([minus]0.23+/-0.22 versus [minus]0.58+/-0.30 mm, P=0.02), (2) reduction in NH (1.48+/-0.58, 2.46+/-1.25, and 2.36+/-1.13 mm2, P&lt;0.01, respectively, for S+ARED, S[minus]ARED, and SCTRL), and (3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH. CONCLUSIONS: The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS is accompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia.</description>
    </item> <item>
      <title>Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling. (Article)</title>
      <link>http://repub.eur.nl/res/pub/4720/</link>
      <pubDate>2003-01-01T00:00:00Z</pubDate>
      <description></description>
    </item> <item>
      <title>Coronary stent traversed volume during the cardiac cycle defined as a target for high-precision radiotherapy by using biplane angiograms. (Article)</title>
      <link>http://repub.eur.nl/res/pub/4793/</link>
      <pubDate>2002-06-24T00:00:00Z</pubDate>
      <description>Three-dimensional reconstructions of 19 coronary artery stents from biplane angiograms were used for measurement of the volume through which the stents traversed during the cardiac cycle. This volume, less than 0.8% of the whole heart volume in all patients, represents a target volume for high-precision radiotherapy to treat coronary artery in-stent restenosis.</description>
    </item> <item>
      <title>Focal In-Stent Restenosis Near Step-Up (Article)</title>
      <link>http://repub.eur.nl/res/pub/4780/</link>
      <pubDate>2002-01-01T00:00:00Z</pubDate>
      <description>A 64-year-old man with exercise-induced chest pain underwent coronary angioplasty of his stenosed left anterior descending coronary artery (segments 6 and 7). We recanalized the artery and placed a 3.0x18-mm stent distally and a 3.0x28-mm stent proximally.</description>
    </item> <item>
      <title>Images in cardiovascular medicine. Focal in-stent restenosis near step-up: roles of low and oscillating shear stress? (Article)</title>
      <link>http://repub.eur.nl/res/pub/9919/</link>
      <pubDate>2002-01-01T00:00:00Z</pubDate>
      <description></description>
    </item> <item>
      <title>Relationship Between Neointimal Thickness and Shear Stress After Wallstent Implantation in Human Coronary Arteries. (Article)</title>
      <link>http://repub.eur.nl/res/pub/4837/</link>
      <pubDate>2001-01-01T00:00:00Z</pubDate>
      <description>Background—In-stent restenosis by excessive intimal hyperplasia reduces the long-term clinical efficacy of coronary stents. Because shear stress (SS) is related to plaque growth in atherosclerosis, we investigated whether variations in SS distribution are related to variations in neointima formation.

Methods and Results—In 14 patients, at 6-month follow-up after coronary Wallstent implantation, 3D stent and vessel reconstruction was performed with a combined angiographic and intravascular ultrasound technique (ANGUS). The bare stent reconstruction was used to calculate in-stent SS at implantation, applying computational fluid dynamics. The flow was selected to deliver an average SS of 1.5 N/m2. SS and neointimal thickness (Th) values were obtained with a resolution of 90° in the circumferential and 2.5 mm in the longitudinal direction. For each vessel, the relationship between Th and SS was obtained by linear regression analysis. Averaging the individual slopes and intercepts of the regression lines summarized the overall relationship. Average Th was 0.44±0.20 mm. Th was inversely related to SS: Th=(0.59±0.24)-(0.08±0.10)xSS (mm) (P&lt;0.05).

Conclusions—These data show for the first time in vivo that the Th variations in Wallstents at 6-month follow-up are inversely related to the relative SS distribution. These findings support a hemodynamic mechanism underlying in-stent neointimal hyperplasia formation.</description>
    </item> <item>
      <title>Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition (Article)</title>
      <link>http://repub.eur.nl/res/pub/9670/</link>
      <pubDate>2001-01-01T00:00:00Z</pubDate>
      <description>BACKGROUND: Constrictive vascular remodeling (VR) is the most significant
          component of restenosis after balloon angioplasty (PTA). Whereas in
          physiological conditions VR is associated with normalization of shear
          stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is
          unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI)
          has been shown to modulate VR after PTA, its effect on the SS and WS
          control mechanisms after PTA is unknown. METHODS AND RESULTS: PTA was
          performed in external iliac arteries of 12 atherosclerotic Yucatan pigs,
          of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10
          vessels) served as controls. Before and after the intervention and at
          6-week follow-up, intravascular ultrasound pullback was performed,
          allowing 3D reconstruction of the treated segment and computational fluid
          dynamics to calculate the media-bounded area and SS. WS was derived from
          the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS
          changed by 20%, 16%, and -49%, respectively, in both groups. VR was
          predicted by SS and WS. In the control group, SS and WS had been
          normalized at follow-up with respect to the reference segment. In
          contrast, for the batimastat group, the SS had been normalized, but not
          the WS. The latter is attributed to an increase in wall area at follow-up.
          CONCLUSIONS: Vascular remodeling after PTA is controlled by both SS and
          WS. MMPI inhibited the WS control system.</description>
    </item> <item>
      <title>Prominent role of tensile stress in propagation of a dissection after coronary stenting: computational fluid dynamic analysis on true 3d-reconstructed segment (Article)</title>
      <link>http://repub.eur.nl/res/pub/9758/</link>
      <pubDate>2001-01-01T00:00:00Z</pubDate>
      <description></description>
    </item> <item>
      <title>Relationship between tensile stress and plaque growth after balloon angioplasty treated with and without intracoronary beta-brachytherapy. (Article)</title>
      <link>http://repub.eur.nl/res/pub/12895/</link>
      <pubDate>2000-12-01T00:00:00Z</pubDate>
      <description>AIMS: We investigated the influence of tensile stress on plaque growth after balloon angioplasty with and without beta-radiation therapy. METHODS AND RESULTS: Thirty-one consecutive patients successfully treated with balloon angioplasty were analysed qualitatively and quantitatively by means of an ECG-gated three-dimensional intravascular ultrasound post-procedure and at follow-up. Eighteen patients were irradiated with catheter-based beta-radiation ((90)Sr/(90)Y source) and 13 were not (control). Studied segments were divided into 2 mm subsegments. Thus 184 irradiated and 111 non-irradiated subsegments were included. Tensile stress was calculated according to Laplace's law. The radiation dose was calculated by means of dose-volume histograms. Plaque growth was positively correlated to tensile stress in both the radiation and control groups (r=0.374, P=0.0001 and r=0.305, P=0.001). Low-dose subsegments (&lt;6 Gy) had a significant correlation (r=0.410, P=0.0001) whereas no correlation was observed in the effective-dose subsegments (&gt; or = 6 Gy). Multivariate analysis identified tensile stress as the only independent predictor of plaque increase in non-irradiated subsegments, whereas actual dose and plaque morphology were stronger predictors in irradiated subsegments. CONCLUSION: The results of this study suggest that plaque growth is related to tensile stress after balloon angioplasty. Intracoronary brachytherapy may alter the biophysical process on plaque growth when the prescribed dose is effectively delivered.</description>
    </item> <item>
      <title>Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress distribution. (Article)</title>
      <link>http://repub.eur.nl/res/pub/4864/</link>
      <pubDate>2000-10-01T00:00:00Z</pubDate>
      <description>Mechanisms of in-stent restenosis are not fully understood. Shear stress is known to play a role in plaque and thrombus formation and is sensitive to changes in regional vessel geometry. Hence, we evaluated the regional changes in 3-D geometry and shear stress induced by stent placement in coronary arteries of pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D geometry was used to calculate locally the curvature, while the shear stress distribution was obtained by computational fluid dynamics. Local changes in shear stress were obtained at the entrance and exit of the stent for baseline (0. 65+/-0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent implantation, the curvature increased by 121% at the entrance and by 100% at the exit of the stent, resulting in local changes in shear stress. In general, at the entrance of the stent local maxima in shear stress were generated, while at the exit both local maxima and minima in shear stress were observed (p&lt;0.05). Additionally, the shear stress at the entrance and exit of the stent were correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation changes 3-D vessel geometry in such a way that regions with decreased and increased shear stress occur close to the stent edges. These changes might be related to the asymmetric patterns of in-stent restenosis.</description>
    </item> <item>
      <title>Shear stress and the vessel wall : in vivo studies applying 3-D finite element modelling (Doctoral Thesis)</title>
      <link>http://repub.eur.nl/res/pub/21295/</link>
      <pubDate>2000-01-19T00:00:00Z</pubDate>
      <description>Atherosclerosis, a degenerative arterial disease, is a leading cause of death in the
western society. It cau cause dysfunction of the heart, stroke or peripheral
vascular disease by limiting the blood supply to the heart, the brain, the
abdominal organs and the legs. The narrowing of those arteries originates from
the build up of 'afherosclerotic' plaques in the arterial wall. Such plaques are the
result of accumulating lipids and accompanying reactive processes into the vessel
wall. Several risk factors are known to induce and innuence the progression of
this disease like hypercholesteremia (Anderson et al., 1987; Davis et al., 1990),
diabetes mellitus (Fontbonne et al., 1989), high blood pressure (Jackson et al.,
1993; Kannel and Higgins, 1990) and smoking (Kannel and Higgins, 1990).
Although these risk factors are systemic in nature, several studies showed that
atherosclerotic plaques are not randomly distributed, but occur with preference to
specific locations in fhe arterial tree. Similarly, after treatment of these
narrowings, it seems fhat highly localized factors are involved in the healing
process. The local nature of atherosclerosis and healing after treatment and their
relation with biophysical factors, particularly shear stress, is the main subject of
this thesis. Before going further into the detail of the locations of these lesions,
first a brief overview is given of fhe process of atherosclerosis and restenosis.</description>
    </item> <item>
      <title>True 3-Dimensional Reconstruction of Coronary Arteries in Patients by Fusion of Angiography and IVUS (ANGUS) and Its Quantitative Validation (Article)</title>
      <link>http://repub.eur.nl/res/pub/4877/</link>
      <pubDate>2000-01-01T00:00:00Z</pubDate>
      <description>Background—True 3D reconstruction of coronary arteries in patients based on intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS information (ANGUS). The clinical applicability of ANGUS was tested, and its accuracy was evaluated quantitatively.

Methods and Results—In 16 patients who were investigated 6 months after stent implantation, a sheath-based catheter was used to acquire IVUS images during an R-wave–triggered, motorized stepped pullback. First, a single set of end-diastolic biplane angiographic images documented the 3D location of the catheter at the beginning of pullback. From this set, the 3D pullback trajectory was predicted. Second, contours of the lumen or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular rotation of the reconstruction was optimized by quantitative matching of the silhouettes of the 3D reconstruction with the actual biplane images. Reconstructions were obtained in 12 patients. The number of pullback steps, which determines the pullback length, closely agreed with the reconstructed path length (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions showed high correlation (0.84 to 0.97) with corresponding measurements in the actual biplane angiographic images.

Conclusions—With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.</description>
    </item> <item>
      <title>Helical Velocity Patterns in a Human Coronary Artery (Article)</title>
      <link>http://repub.eur.nl/res/pub/4879/</link>
      <pubDate>2000-01-01T00:00:00Z</pubDate>
      <description>A74-year-old man was referred to our catheterization laboratory for elective angioplasty of the right coronary artery (RCA). One year earlier, he had suffered an acute inferior myocardial infarction, which was successfully treated with intravenous streptokinase. Only minor creatinine phosphokinase elevations were found.</description>
    </item> <item>
      <title>Helical velocity patterns in a human coronary artery: a three-dimensional computational fluid dynamic reconstruction showing the relation with local wall thickness (Article)</title>
      <link>http://repub.eur.nl/res/pub/9423/</link>
      <pubDate>2000-01-01T00:00:00Z</pubDate>
      <description></description>
    </item>
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