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The aim of this study was to investigate the relationship between the plaque free wall (PFW) measured by optical coherence tomography (OCT) and the plaque burden (PB) measured by intravascular ultrasound (IVUS). We hypothesize that measurement of the PFW could help to estimate the PB, thereby overcoming the limited ability of OCT to visualize the external elastic membrane in the presence of plaque. This could enable selection of the optimal stent-landing zone by OCT, which is traditionally defined by IVUS as a region with a PB < 40 %. PB (IVUS) and PFW angle (OCT and IVUS) were measured in 18 matched IVUS and OCT pullbacks acquired in the same coronary artery. We determined the relationship between OCT measured PFW (PFWOCT) and IVUS PB (PBIVUS) by non-linear regression analysis. An ROC-curve analysis was used to determine the optimal cut-off value of PFW angle for the detection of PB < 40 %. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. There is a significant correlation between PFWOCT and PBIVUS (r(2) = 0.59). The optimal cut-off value of the PFWOCT for the prediction of a PBIVUS < 40 % is ≥220° with a PPV of 78 % and an NPV of 84 %. This study shows that PFWOCT can be considered as a surrogate marker for PBIVUS, which is currently a common criterion to select an optimal stent-landing zone., Competing Interests: Compliance with ethical standards The Erasmus MC has a patent licensing agreement with Terumo Corporation. Dr. Van Soest has the rights to receive royalties as part of this agreement. The other authors declare that they have no conflict of interest. Informed consent was obtained from all individual participants included in the study. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

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., (© 2014 Wiley Periodicals, Inc.)

Aims: At present it is unknown what limits the arterial remodeling process during atherosclerotic plaque formation. In healthy arteries remodeling is regulated by the shear stress induced response by the endothelium. As endothelium at the plaque site is assumed to be dysfunctional, we tested the hypothesis that plaque free wall (PFW) determines vascular remodeling during atherosclerotic plaque build-up., Methods & Results: 66 human coronary ROIs (38 patients) were studied at baseline and at 3 years follow up applying intravascular ultrasound (IVUS). From the IVUS images the lumen and external elastic membrane contours were delineated to assess wall thickness (WT), vessel area (VA), Plaque Area (PA) and plaque burden (PA/VA*100%). WT < 0.5 mm was defined as normal and determined the arc of the PFW (0-360°). Positive remodeling was defined as relative difference of VA over time >5%. At baseline, IVUS-PFW was inversely related to plaque burden (p < 0.05). Positive remodeling was most frequently observed in ROIs with IVUS-PFW > 180° (i.e. larger than half of the circumference) compared to PFW < 180° (55% vs. 12%, p < 0.05). Accordingly, plaques with IVUS-PFW > 180° at baseline had the largest change in VA (1.1 ± 2.1 vs. -0.4 ± 0.6 mm(2), p < 0.05) with an odds ratio of 9.2 to develop positive remodeling., Conclusions: Our serial IVUS data show that IVUS-PFW is a determinant of vascular remodeling. ROIs with PFW > 180 at baseline had the highest probability to undergo positive remodeling., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Heterogeneity in plaque composition in human coronary artery bifurcations is associated with blood flow induced shear stress. Shear stress is generally determined by combing 3D lumen data and computational fluid dynamics (CFD). We investigated two new procedures to generate 3D lumen reconstructions of coronary artery bifurcations for shear stress computations., Methods: We imaged 10 patients with multislice computer tomography (MSCT) and intravascular ultrasound (IVUS). The 3D reconstruction of the main branch was based on the fusion of MSCT and IVUS. The proximal part of side branch was reconstructed using IVUS data or MSCT data, resulting in two different reconstructions of the bifurcation region. The distal part of the side branch was based on MSCT data alone. The reconstructed lumen was combined with CFD to determine the shear stress. Low and high shear stress regions were defined and shear stress patterns in the bifurcation regions were investigated., Results: The 3D coronary bifurcations were successfully generated with both reconstruction procedures. The geometrical features of the bifurcation region for the two reconstruction procedures did not reveal appreciable differences. The shear stress maps showed a qualitative agreement, and the low and high shear stress regions were similar in size and average shear stress values were identical. The low and high shear stress regions showed an overlap of approximately 75%., Conclusion: Reconstruction of the side branch with MSCT data alone is an adequate technique to study shear stress and wall thickness in the bifurcation region. The reconstruction procedure can be applied to further investigate the effect of shear stress on atherosclerosis in coronary bifurcations., (© 2013 Published by Elsevier Ltd.)

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.

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.

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.

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., (Copyright © 2011 Wiley Periodicals, Inc.)

Objective: We evaluated the ability of 64-slice multidetector computed tomography (MDCT)-derived plaque parameters to detect and quantify coronary atherosclerosis, using intravascular ultrasound (IVUS) as the reference standard., Methods: In 32 patients, IVUS and 64-MDCT was performed. The MDCT and IVUS datasets of 44 coronary arteries were co-registered using a newly developed fusion technique and quantitative parameters were derived from both imaging modalities. The threshold of >0.5 mm of maximum wall thickness was used to establish plaque presence on MDCT and IVUS., Results: We analyzed 1364 coregistered 1-mm coronary cross-sections and 255 segments of 5-mm length. Compared with IVUS, 64-MDCT enabled correct detection in 957 of 1109 cross-sections containing plaque (sensitivity 86%). In 180 of 255 cross-sections atherosclerosis was correctly excluded (specificity 71%). On the segmental level, MDCT detected 213 of 220 segments with any atherosclerotic plaque (sensitivity 96%), whereas the presence of any plaque was correctly ruled out in 28 of 32 segments (specificity 88%). Interobserver agreement for the detection of atherosclerotic cross-sections was moderate (Cohen's kappa coefficient K=0.51), but excellent for the atherosclerotic segments (K=1.0). Pearson's correlation coefficient for vessel plaque volumes measured by MDCT and IVUS was r=0.91 (p<0.001). Bland-Altman analysis showed a slight non-significant underestimation of any plaque volume by MDCT (p=0.5), with a trend to underestimate noncalcified and overestimate mixed/calcified plaque volumes (p=0.22 and p=0.87 respectively)., Conclusion: MDCT is able to detect and quantify atherosclerotic plaque. Further improvement in CT resolution is necessary for more reliable assessment of very small and distal coronary plaques., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2010 Wiley-Liss, Inc.)

Aims: Atherosclerotic plaques develop in low shear stress regions. In the more advanced phase of the disease, plaques are exposed to altered shear stress levels, which could influence plaque composition. We investigated changes in plaque composition in human coronary arteries over a 6-month period and how these changes are related to shear stress., Methods and Results: We took images of eight coronary arteries to obtain the 3D shape of the arteries. Lumen data were combined with computational fluid dynamics to obtain shear stress. Palpography was applied to measure strain at baseline and at 6-month follow-up. The change in strain from baseline to follow-up served as a marker for the change in plaque composition. We identified 17 plaques, and each plaque was divided into four regions: the upstream, throat, shoulder and downstream region. Shear stress and strain in the downstream region was significantly lower than in the other regions. There was no significant change in strain for the four different plaque regions. However, we observed that those plaque regions exposed to high shear stress showed a significant increase in strain., Conclusions: Plaque regions exposed to high shear stress showed an increase in strain over time. This indicates that shear stress may modulate plaque composition in human coronary arteries.

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 ± 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 ≤ 0.049 mm, ≤ 0.056 mm, ≤ 2.77%, and 1.6°, respectively. Agreement between models for MLD, RVD, and DS was ± 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 >0.7 mm in excellent agreement with the true dimensions., (Copyright © 2011 Wiley-Liss, Inc.)

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 < 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., (Copyright 2009 Wiley-Liss, Inc.)

Objectives: (i) To explore the relation between greyscale intravascular ultrasound (IVUS) plaque qualitative classification and IVUS radiofrequency data (RFD) analysis tissue types; (ii) to evaluate if plaque composition as assessed by RFD analysis can be predicted by visual assessment of greyscale IVUS images., Methods: In 120 IVUS-RFD cross-sections, a sector of the plaque with homogenous tissue composition (e.g., fibrous, fibrofatty, necrotic core, and dense calcium) was selected. Two experienced observers analyzed twice the corresponding greyscale IVUS images to: (1) classify the selected sectors according to greyscale IVUS plaque type classification and (2) predict the tissue type expected in the sector by RFD analysis., Results: In the greyscale IVUS plaque type classification, the observers agreed in 90/120 sectors (kappa = 0.64). Calcified, soft and mixed plaques by greyscale IVUS classification were mainly composed of dense calcium, fibrofatty, and necrotic core, respectively, in the RFD analysis. The plaques classified in greyscale IVUS as fibrous were actually fibrous tissue by IVUS RFD in only 30% of the cases. Overall, high interobserver variability in the prediction of RFD results by visual assessment of greyscale IVUS images (kappa = 0.23 for observer 1 and 0.55 for observer 2) was found. Sensitivities for detection of calcified tissue and NC by greyscale IVUS visual assessment were 88% and 58%, respectively., Conclusions: High interobserver variability in the prediction of tissue type by visual assessment of greyscale IVUS images was observed. This underlines the need of quantitative methods for the analysis of the ultrasound characteristics of coronary plaque components.

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.

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 3mm. 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.

Background: Virtual histology (VH) uses intravascular ultrasound (IVUS) radiofrequency spectral analysis to locally identify the morphology and composition of atherosclerotic plaques. We sought to explore in vivo the relation between IVUS-derived thin cap fibro-atheroma (IDTCFA) and remodelling index in patients with acute coronary syndromes using IVUS-VH., Methods and Results: Twenty-one patients (63 vessels) were enrolled. When compared to cross sectional areas (CSAs) without necrotic core in contact with the lumen (NCCL), CSAs with NCCL had a larger plaque burden 42.8+/-11.5% vs. 32.8+/-11.5%, p<0.001; higher overall necrotic core content [13.8+/-10.7% vs. 2.3+/-7.9% (p<0.001)] and calcified tissue [4.7+/-6.5 vs. 0.66+/-2.1% (p<0.001)]. On average there were 2 IVUS-derived thin cap fibro-atheroma (IDTCFA) per patient. Nearly half of the IDTCFAs had positive remodelling., Conclusions: CSAs with NCCL had worse morphological profiles than those with no NCCL. The simultaneous and more detailed assessment of IDTCFA and remodelling index identifies a reduced number of allegedly high-risk plaques. The findings of this study may have important clinical implications, since they shed light into a possible method of identiying potentially high-risk plaques suitable for pharmacological and/or local treatment.

Blood-flow-induced shear stress acting on the arterial wall is of paramount importance in vascular biology. Endothelial cells sense shear stress and largely control its value in a feedback-control loop by adapting the arterial dimensions to blood flow. Nevertheless, to allow for variations in arterial geometry, such as bifurcations, shear stress control is modified at certain eccentrically located sites to let it remain at near-zero levels. In the presence of risk factors for atherosclerosis, low shear stress contributes to local endothelial dysfunction and eccentric plaque build up, but normal-to-high shear stress is atheroprotective. Initially, lumen narrowing is prevented by outward vessel remodeling. Maintenance of a normal lumen and, by consequence, a normal shear stress distribution, however, prolongs local unfavorable low shear stress conditions and aggravates eccentric plaque growth. While undergoing such growth, eccentric plaques at preserved lumen locations experience increased tensile stress at their shoulders making them prone to fissuring and thrombosis. Consequent loss of the plaque-free wall by coverage with thrombus and new tissue may bring shear-stress-controlled lumen preservation to an end. This change causes shear stress to increase, which as a new condition may transform the lesion into a rupture-prone vulnerable plaque. We present a discussion of the role of shear stress, in setting the stage for the generation of rupture-prone, vulnerable plaques, and how this may be prevented.

The average low shear stress (SS) is known to determine predilection sites of atherosclerotic plaques. However, as plaques encroach into the lumen and thereby increase SS, interpretation of patient-specific data obtained at one moment in time regarding the influence of SS in the generation of atherosclerosis is not straightforward. This study aims to compare two methods of data analysis for the aid of data interpretation: (a) point-wise analysis of the raw data, (b) global analysis: to assess the history related natural SS distribution in coronary arteries by averaging the data in the axial vessel direction. Normal to mildly diseased human coronary arteries were investigated applying a combination of 3-D reconstruction technique and computational fluid dynamics (CFD). Point-wise analysis relating local wall thickness to local SS showed in only 4% of the cases an inverse relationship. In contrast, averaging the data in the axial vessel direction, showed in 38% a significant inverse relation between wall thickness and SS, resulting in an average negative slope of -0.70+/-0.46 mm/Pa. These data suggest that using a geometry guided way of data averaging may reveal history related effects of SS, which in part explains localization of atherosclerotic plaques.

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.

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.

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 <50%) was investigated with ANGiography and ivUS (ANGUS) to provide 3D lumen and wall geometry. Selection of segments >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<0.05) and VR was positive (7+/-9%, P<0.05). Narrowed segments (n=13, 1 excluded, AS=18+/-6%, P<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.

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.

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.

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/m(2). SS and neointimal thickness (Th) values were obtained with a resolution of 90 degrees 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<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.

Plaque volume determined by common linear 3-D IVUS analysis systems will show under- or overestimation in curved vessel segments because these systems approximate the true 3-D transducer pull-back trajectory by a straight line. We developed a mathematical model that showed that the error is primarily dependent on the curvature of the pull-back trajectory and not on vessel tortuosity. Furthermore, we measured this error in vivo in the coronary arteries of 15 patients, comparing the plaque volume using a true 3-D reconstruction method with that of the linear approach. The in vivo plaque volume error ranged from 2.3% to -1.2% for 15 coronary segments with lengths ranging from 38.8 to 89.1 mm (62.2 +/- 13 mm). The volume error introduced by linear 3-D IVUS analysis systems is dependent on the curvature of the pull-back trajectory. The error measured in vivo was small and inversely related to segment length.

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 REUSLTS: 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.

Shear stress plays a role in lipid accumulation in primary atherosclerosis and vascular remodelling. We will present applications of a new technique, which enables to quantify shear stress in 3D vessel reconstructions. The method is based on 3D IVUS reconstructions of blood vessels either obtained by IVUS pull back (external iliac artery) or by a combination of angiography and IVUS (curved coronary artery). Distribution of wall thickness of a curved human right coronary artery was such that low wall thickness occurred where shear stress was high, and wall thickness was high where shear stress was low. Consequently, an inverse relationship between shear stress and wall thickness was detected. Although vascular remodelling after PTA in external iliac arteries of atherosclerotic Yucatan pigs was predicted both by acute gain and decrements in shear stress, the decrement in shear stress appeared a better predictor. In conclusion, shear stress appears to play a role in primary atherosclerosis and vascular remodelling after PTA.

The predilection sites of atherosclerotic plaques implicate rheologic factors like shear stress underlying the genesis of atherosclerosis. Presently no technique is available that enables one to provide 3D shear stress data in human coronary arteries in vivo. In this study, we describe a novel technique that uses a recently developed 3D reconstruction technique to calculate shear stress on the endothelium with computational fluid dynamics. In addition, we calculated local wall thickness, the principal plane of curvature, and the location of plaque with reference to this plane, relating these results to shear stress in a human right coronary artery in vivo. Wall thickness and shear stress values for the entire vessel for three inflow-velocity values (10 cm/second, 20 cm/second, and 30 cm/second equivalents with the Reynolds numbers 114,229, and 457) were as follows: 0.65 +/- 0.37 mm (n = 1600) and 19.6 +/- 1.7 dyne/cm2; 46.1 +/- 8.1 dyne/cm2 and 80.1 +/- 16.8 dyne/cm2 (n = 1600). Curvature was 25 +/- 9 (m-1), resulting in Dean numbers 20 +/- 8; 46 +/- 16, and 93 +/- 33. Selection of data at the inner curvature of the right coronary artery provided wall thickness values of 0.90 +/- 0.41 mm (n = 100), and shear stress was 17 +/- 17, 38 +/- 44, and 77 +/- 54 dyne/cm2 (n = 100), whereas wall thickness values at the outer curve were 0.37 +/- 0.17 mm (n = 100) and shear stress values were 22 +/- 17, 60 +/- 44, and 107 +/- 79 dyne/cm2 (n = 100). These findings could be reconciled by an inverse relationship between wall thickness and shear stress for each velocity level under study. For the first time for human vessels in vivo, evidence is presented that low shear stress promotes atherosclerosis. As the method is nondestructive, it allows repeated measurements in the same patient and will provide new insights in the progress of atherosclerosis.

Objective: Air bubbles entering the coronary artery may have harmful effects on cardiac function. From the physical point of view it is the relatively high surface tension of the blood-air interface which causes bubbles to trap in small vessels. The aim of the present study was to reduce depression of myocardial function from air embolism by lowering the surface tension of air bubbles., Methods: The effect of using antifoam as a surface-tension-reducing agent on air bubble entrapment and cardiac function was investigated in 6 anesthetized pigs (27 +/- 1 kg) and analyzed using a two-compartment diffusion model. Air bubbles with a diameter of 150 microns were selectively injected into the left anterior descending coronary artery (LADCA) in a carrying fluid in the presence or absence of antifoam. Myocardial systolic segment shortening in the LADCA region (SS-LADCA) was measured by sonomicrometry. Presence of emboli was detected by measuring the amount of reverberation of ultrasound scattered by trapped air bubbles., Results: SS-LADCA transiently decreased after injections of air bubbles in both the absence and presence of antifoam. However, in the presence of antifoam the regional depression recovered to normal sooner, the average depth of the depression was reduced, and bubbles from the embolized area cleared faster. These observations can be explained by a model derived from Laplace's law.

At present a rapidly expanding variety of methods appear to provide three-dimensional (3-D) reconstructions of blood vessels in a patient. Generally the results of such methods look very realistic. However, only a few produce a true 3-D reconstruction. We strongly suggest that for a true 3-D reconstruction of a blood vessel the following criteria should at least be fulfilled: (1) the arterial wall rather than the lumen must be reconstructed; (2) the spatially curved course of the vessel must be included; and (3) the orientation of local vessel wall characteristics, for example, plaque eccentricity, with respect to the luminal course must be correctly maintained. Currently, only methods combining biplane X-ray angiography and intravascular ultrasound imaging (IVUS) have succeeded in providing true 3-D reconstruction of a segment of a vessel. Accuracy of those reconstructions is derived from studies using phantoms having precisely known geometry. In patients, data on accuracy are more difficult to obtain. Nevertheless, a comparison can be made between the actual length of an IVUS pull-back trajectory and its reconstructed length showing relative differences of less than 3%. Further knowledge can be obtained by comparing simulated angiograms derived from the 3-D reconstruction with the real contrast angiograms. True 3-D reconstruction methods of the vessel wall and lumen, applicable in the individual patient, have become feasible and produce accurate results. Application of such a method will be helpful to understand immediate and long-term vessel remodelling induced by all types of catheter interventions and in the study of progression or regression of atherosclerotic wall disease.

Currently, automated systems for quantitative analysis by intracoronary ultrasound (ICUS) are restricted to the detection of the lumen. The aim of this study was to determine the accuracy and reproducibility of a new semiautomated contour detection method, providing off-line identification of the intimal leading edge and external contour of the vessel in three-dimensional ICUS. The system allows cross-sectional and volumetric quantification of lumen and of plaque. It applies a minimum-cost algorithm and the concept that edge points derived from previously detected longitudinal contours guide and facilitate the contour detection in the cross-sectional images. A tubular phantom with segments of various luminal dimensions was examined in vitro during five catheter pull-backs (1 mm/sec), and subsequently 20 diseased human coronary arteries were studied in vivo with 2.9F 30 MHz mechanical ultrasound catheters (200 images per 20 mm segment). The ICUS measurements of phantom lumen area and volume revealed a high correlation with the true phantom areas and volumes (r = 0.99); relative mean differences were -0.65% to 3.86% for the areas and 0.25% to 1.72% for the volumes of the various segments. Intraob-server and interobserver comparisons showed high correlations (r = 0.95 to 0.98 for area and r = 0.99 for volume) and small mean relative differences (-0.87% to 1.08%), with SD of lumen, plaque, and total vessel measurements not exceeding 7.28%, 10.81%, and 4.44% (area) and 2.66%, 2.81%, and 0.67% (volume), respectively. Thus the proposed analysis system provided accurate measurements of phantom dimensions and can be used to perform highly reproducible area and volume measurements in three-dimensional ICUS in vivo.

Aim of this study is the assessment of feasibility and clinical usefulness of a new index of stenosis severity, the slope of the instantaneous transstenotic pressure gradient/velocity relationship. Twenty-one patients scheduled for percutaneous revascularization procedures were studied with simultaneous measurement of poststenotic coronary pressure and flow velocity, in basal condition and during maximal hyperemia induced with intracoronary papaverine. Reliable measurements of the transstenotic pressure gradient/velocity relationship could be obtained in 11 patients. In 64% of the cases, a quadratic equation showed the best fit for the data. Steeper increases of the transstenotic pressure gradient at any given velocity increase were observed in the lesions with the smallest cross-sectional area measured with quantitative angiography. A comparison of this new index with coronary flow reserved, maximal hyperemic velocity, stenosis flow reserve derived from quantitative angiography, basal and hyperemic transstenotic pressure gradient and fractional flow reserve is presented and the relative merits of all these parameters are discussed. This pilot experience suggests that the instantaneous relationship between pressure gradient and flow velocity changes during the cardiac cycle can accurately characterize the stenosis hemodynamics in the catheterization laboratory.

Colors in video representations of angioscopic images are up until now described by an human observer. Differences in settings of the monitor and the inherent poor ability of the human eye to classify colors objectively results in a very poor intraobserver as well as interobserver variability. A PC-based method is described to measure colors in a video image and to present the results in a novel C-diagram. Results with this method for standard calibrated colors are given. Possible sources of error are discussed and methods to minimize these errors are presented.

Intravascular angioscopy has been hampered by its limitation in quantifying obtained images. To circumvent this problem, a lightwire was used, which projects a ring of light onto the endoluminal wall in front of the angioscope. This investigation was designed to quantify luminal dimensions of casts from stenotic human coronary arteries and to investigate the feasibility of performing volume reconstruction. Angioscopic video recordings were made during simultaneous motorized pullback (2 mm/s) of an angioscopic catheter and light-emitting fiber through 4 epoxy casts from human coronary arteries. Quantification of the images was performed using a computerized cross-sectional area measurement system. The coronary casts were divided into cross-sectional segments of 4 to 10 mm in thickness, with the true volume of each segment determined by means of a microdispenser. Because of vessel curvature and luminal narrowing, complete visualization of the ring of light at all 1-mm-distant locations was only possible in 19 of 40 segments. For these 19 segments, linear regression analysis showed a good correlation between measured and true segmental volume (r = 0.97, y = 0.88x + 6.58 mm3, standard error of estimate = 3.48 mm3). The relative error in the measured segmental volumes was 3.9 +/- 7.1% (mean +/- SD). These initial results of endoluminal volume reconstruction demonstrate the feasibility of this technique in vitro with high accuracy and low variability, but further technical improvements are necessary to increase the success rate, especially in the quantitative assessment of vessels with complex morphology.

The design features of the cutting electrode and the electrical characteristics of a monopolar electrosurgical device were specially adapted for performing a septal myectomy in patients with hypertrophic obstructive cardiomyopathy. Both the cutting behavior and electrode design were found to facilitate myectomy.

A polyethylene-terephthalate (PETP, polyester), self-expanding, braided mesh stent has been developed for percutaneous (coronary) arterial implantation. In vitro measurements showed that the radial pressure delivered by this device was similar to a self-expanding, stainless steel stent. Due to hysteresis-like behaviour, it proved necessary to mount the polymer stent on the delivery system immediately before the placement procedure, and to select a diameter in the unconstrained condition, which was 60% larger than the diameter of the target vessel. Eight polyester stents were implanted in peripheral arteries of four pigs. Except for heparin during the implantation procedure, antithrombotic or antiplatelet drugs were not administered. After four weeks repeat angiography revealed that one of the stents was subtotally occluded. At autopsy, two other stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative angiographic assessment showed that the mean luminal diameters at the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 2.7 +/- 0.5 mm at four weeks after implantation. Intravascular ultrasound (IVUS) examination after 4 weeks could identify the individual struts of the stents, as well as their length. In addition, a description of the extent of neointimal hyperplasia was feasible. The IVUS assessment was validated by histological examination. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at four weeks. Imaging of stents by angiography and IVUS provided complementary information.

By its nature, vaporization of atherosclerotic plaques by laser irradiation or spark erosion may produce a substantial amount of gas. To evaluate the effect of gas embolism possibly caused by vaporization techniques, air bubbles with diameters of 75, 150, or 300 microns, each in a volume of 2 microliters/kg, were selectively injected subproximal in the left anterior descending coronary artery of seven anesthetized pigs (28 +/- 3 kg). Systemic hemodynamics such as heart rate, left ventricular pressure and its peak positive first derivative, and mean arterial pressure did not change after air injection, whereas there was a minor change in peak negative first derivative of left ventricular pressure. After injection of air bubbles there was a maximal relative reduction of systolic segment shortening (SS) in the myocardium supplied by the left anterior descending coronary artery of 27, 45, and 58% for 75-, 150-, and 300-microns bubbles, respectively, and a relative increase of postsystolic SS (PSS) of 148, 200, and 257% for 75-, 150-, and 300-microns bubbles, respectively. Recovery of SS and PSS started after 2 min and was completed after 10 min. A difference in SS and PSS changes between different bubble size injections could be demonstrated. From this study it is clear that depression of regional myocardial function after injection of air bubbles could pass unnoticed on the basis of global hemodynamic measurements.

Tissue cutting by electrosurgery is often accompanied with stimulation of nerves and muscles, despite the high frequency of the alternating current being applied. The main source of this stimulation is thought to be the generation of low frequency current by the nonlinear sparking process. However, measurement of this low-frequency current, in the generator electrode's circuit, showed relatively small values, barely sufficient to support this hypothesis. In this study more powerful low frequency current could be identified, indeed also originating from the nonlinear sparking process. Local direct and low frequency currents, at a level of tens of milliamperes, appeared to be generated between different sites of the active electrode-tissue interface. Probably these local currents have not been noticed before as they cannot be detected in the outer chain of generator, electrodes, and connecting wires. This finding may explain why most measures, intended to prevent stimulation by modifying this outer chain, had only limited success.

A polyethylene-terephthalate braided mesh stent has been developed for application in the (coronary) arterial tree. In vitro measurements showed that the radial pressure delivered by this device was in the same range as that of a stainless steel stent. Hysteresis-like behavior, however, occurred after constraining the polyester stent for a period of only 15 minutes on a delivery system for percutaneous implantation. This implies that the polymer stent must be mounted on this delivery system immediately before the placement procedure, and that either a diameter in the unconstrained condition must be selected, which is considerably larger than the diameter of the target vessel, or stent expansion has to be enhanced by balloon expansion. Taking into account the results obtained during the in vitro studies, we investigated the angiographic patency and histologic features after implantation of this polyester stent in peripheral arteries of pigs. In four animals eight stents were placed. Except for heparin during the implantation procedure only, antithrombotic or antiplatelet drugs were not administered. After 4 weeks repeat angiography was performed. Angiography revealed that five of the six correctly placed stents were patent. At autopsy, two additional patent stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative assessment showed that the mean luminal diameters of the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 3.1 +/- 0.3 mm at 4 weeks after implantation. Histology demonstrated an inflammatory reaction of variable severity around the stent fibers. Quantitative histologic measurements showed that the thickness of the neointima was 114 +/- 38 mum after 4 weeks. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. Hysteresis-like behavior of polyester stents, however, influences the selection of the nominal stent diameter as well as the forces exerted to the vessel wall. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at 4 weeks. The extent of neointimal proliferation was similar to that observed after placement of metal stents in swine, despite the presence of a more pronounced inflammatory reaction.

Electrical impedance measurements were performed on 13 atherosclerotic human aortic segments at 67 measuring spots in order to determine whether or not on the basis of these data a distinction can be made between atherosclerotic lesions and normal tissue. Stenosis localization and guidance of interventional techniques could be among the applications of an impedance measuring technique implemented on a catheter system. The experimental results, obtained with a two-electrode measuring technique, show that the apparent resistivity of an atherosclerotic spot does not necessarily deviate much from the resistivity of normal tissue. This is clarified by histology which shows that the majority of lesions has a surface layer of connective, fibrous tissue having almost similar conducting properties as the normal arterial wall. For gaining a deeper understanding of the way in which the measured data come about, a physical model of an atherosclerotic lesion is presented and confronted with the data. Both experimental data and theoretical considerations lead to the conclusion that only when the superficial fibrous layer is absent or very thin in relation to the size of the measuring electrode, the measured resistivity at a lesion is much higher than at normal spots. This occurs as a consequence of the high ohmic properties of the calcified or lipid deposits in the atherosclerotic lesion.

An alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and documented histologically in vitro from 30 atherosclerotic segments of six human aortic autopsy specimens. Craters with a constant area and a depth that varied according to the duration of application were produced. The method was confirmed to be electrically safe during preliminary in vivo trials in the coronary arteries of seven anesthetized pigs. The main advantages of this technique are that it is simpler to execute than laser irradiation and potentially more controllable.

In this study the hypothesis is tested that the motion pattern of small anatomic landmarks, recognizable at the left ventricular endocardial border in the contrast angiocardiogram, reflects the motion of the endocardial wall. To verify this, minute metal markers were inserted in the endocardium of eight pigs with a novel retrograde transvascular approach. Marker motion was subsequently recorded with roentgen cinematography and compared with the motion of the landmarks on the endocardial contours detected from the contrast ventriculogram with an automated contour detection system. Linear regression analysis of the directions of the systolic metal marker and endocardial landmark pathways yielded a correlation coefficient of 0.86 and a standard error of the estimate of 10.3 degrees. Landmark pathways were also measured in 23 normal human left ventriculograms. Normal left ventricular endocardial wall motion during systole, as observed in the 30 degrees right anterior oblique view, is characterized by a dominant inward transverse motion of the opposite anterior and inferoposterior walls and a descent of the base toward the apex. The apex itself is almost stationary. On the basis of these observations, a widely applicable model for the assessment of left ventricular wall motion is described in mathematical terms.