The association between antiplatelet therapy and changes in intraplaque hemorrhage in patients with mild to moderate symptomatic carotid stenosis: a longitudinal MRI study.

INTRODUCTION: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular events. A positive association between previous antiplatelet use and IPH was reported in a cross-sectional analysis. We investigated changes in IPH over two years in patients who recently started versus those with continued antiplatelet use. METHODS: In the Plaque at Risk (PARISK) study, symptomatic patients with <70% ipsilateral carotid stenosis underwent carotid plaque MRI at baseline and after two years to determine IPH presence and volume. Participants were categorized into new users (starting antiplatelet therapy following the index event) and continued users (previous use of antiplatelet therapy before the index event). The association between previous antiplatelet therapy and the presence of IPH at baseline MRI was investigated using multivariable logistic regression analysis. IPH volume change over a period of two years, defined as the difference in volume between follow-up and baseline, was investigated in each group with a Wilcoxon signed-rank test. The IPH volume change was categorized as progression, regression, or no change. Using multivariable logistic regression, we investigated the association between new antiplatelet use and 1) newly developed ipsilateral or contralateral IPH and 2) IPH volume progression. RESULTS: A total of 108 patients underwent carotid MRI at baseline and follow-up. At baseline, previous antiplatelet therapy was associated with any IPH (OR=5.6, 95% CI: 1.3-23.1; p=0.02). Ipsilateral IPH volume did not change significantly during the two years in patients who continued receiving antiplatelet agents (86.4 mm3 [18.2-235.9] vs. 59.3 mm3 [11.4-260.3]; p=0.6) nor in the new antiplatelet users (n=31) (61.5 mm3 [0.0-166.9] vs. 27.7 mm3 [9.5-106.4]; p=0.4). Similar results of a nonsignificant change in contralateral IPH volume during those two years were observed in both groups (p>0.05). No significant associations were found between new antiplatelet use and newly developed IPH at two years (odds ratio (OR)=1.0, 95% CI:0.1-7.4) or the progression of IPH (ipsilateral: OR=2.4, 95% CI:0.3-19.1; contralateral: OR=0.3, 95% CI:0.01-8.5). CONCLUSION: Although the baseline association between IPH and previous antiplatelet therapy was confirmed in this larger cohort, the new onset of antiplatelet therapy after TIA/stroke was not associated with newly developed IPH or progression of IPH volume over the subsequent two years.

Association between Intraplaque Hemorrhage and Vascular Remodeling in Carotid Arteries: The Plaque at RISK (PARISK) Study.

INTRODUCTION: Vascular remodeling is a compensatory enlargement of the vessel wall in response to atherosclerotic plaque growth. We aimed to investigate the association between intraplaque hemorrhage (IPH), vascular remodeling, and luminal dimensions in recently symptomatic patients with mild to moderate carotid artery stenosis in which the differences in plaque size were taken into account. MATERIALS AND METHODS: We assessed vessel dimensions on MRI of the symptomatic carotid artery in 164 patients from the Plaque At RISK study. This study included patients with recent ischemic neurological event and ipsilateral carotid artery stenosis <70%. The cross section with the largest wall area (WA) in the internal carotid artery (ICA) was selected for analysis. On this cross section, the following parameters were determined: WA, total vessel area (TVA), and lumen area (LA). Vascular remodeling was quantified as the remodeling ratio (RR) and was calculated as TVA at this position divided by the TVA in an unaffected distal portion of the ipsilateral ICA. Adjustment for WA was performed to correct for plaque size. RESULTS: Plaques with IPH had a larger WA (0.56 vs. 0.46 cm2; p < 0.001), a smaller LA (0.17 vs. 0.22 cm2; p = 0.03), and a higher RR (2.0 vs. 1.9; p = 0.03) than plaques without IPH. After adjustment for WA, plaques containing IPH had a smaller LA (B = -0.052, p = 0.01) than plaques without IPH, but the RR was not different. CONCLUSION: After correcting for plaque size, plaques containing IPH had a smaller LA than plaques without IPH. However, RR was not different.

Contrast-enhanced micro-CT imaging in murine carotid arteries: a new protocol for computing wall shear stress.

BACKGROUND: Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. To determine WSS in vivo, detailed 3D geometry of the vessel network is required. However, a protocol to reconstruct 3D murine vasculature using this animal model is lacking. In this project, we evaluated the adequacy of eXIA 160, a small animal contrast agent, for assessing murine vascular network on micro-CT. Also, a protocol was established for vessel geometry segmentation and WSS analysis. METHODS: A tapering cast was placed around the right common carotid artery (RCCA) of ApoE-/- mice (n = 8). Contrast-enhanced micro-CT was performed using eXIA 160. An innovative local threshold-based segmentation procedure was implemented to reconstruct 3D geometry of the RCCA. The reconstructed RCCA was compared to the vessel geometry using a global threshold-based segmentation method. Computational fluid dynamics was applied to compute the velocity field and WSS distribution along the RCCA. RESULTS: eXIA 160-enhanced micro-CT allowed clear visualization and assessment of the RCCA in all eight animals. No adverse biological effects were observed from the use of eXIA 160. Segmentation using local threshold values generated more accurate RCCA geometry than the global threshold-based approach. Mouse-specific velocity data and the RCCA geometry generated 3D WSS maps with high resolution, enabling quantitative analysis of WSS. In all animals, we observed low WSS upstream of the cast. Downstream of the cast, asymmetric WSS patterns were revealed with variation in size and location between animals. CONCLUSIONS: eXIA 160 provided good contrast to reconstruct 3D vessel geometry and determine WSS patterns in the RCCA of the atherosclerotic mouse model. We established a novel local threshold-based segmentation protocol for RCCA reconstruction and WSS computation. The observed differences between animals indicate the necessity to use mouse-specific data for WSS analysis. For our future work, our protocol makes it possible to study in vivo WSS longitudinally over a growing plaque.

Use of Antiplatelet Agents Is Associated With Intraplaque Hemorrhage on Carotid Magnetic Resonance Imaging: The Plaque at Risk Study.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging. METHODS: Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH. RESULTS: IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12-6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH. CONCLUSIONS: In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.

Plaque components in symptomatic moderately stenosed carotid arteries related to cerebral infarcts: the plaque at RISK study.

BACKGROUND AND PURPOSE: Carotid plaque composition is a major determinant of cerebrovascular events. In the present analysis, we evaluated the relationship between intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (TRFC) in moderately stenosed carotid arteries and cerebral infarcts on MRI in the ipsilateral hemisphere. METHODS: A total of 101 patients with a symptomatic 30% to 69% carotid artery stenosis underwent MRI of the carotid arteries and the brain, within a median time of 45 days from onset of symptoms. The presence of ipsilateral infarcts in patients with and without IPH and TRFC was evaluated. RESULTS: IPH was seen in 40 of 101 plaques. TRFC was seen in 49 of 86 plaques (postcontrast series were not obtained in 15 patients). In total, 51 infarcts in the flow territory of the symptomatic carotid artery were found in 47 patients. Twenty nine of these infarcts, found in 24 patients, were cortical infarcts. No significant relationship was found between IPH or TRFC and the presence of ipsilateral infarcts. CONCLUSIONS: MRI detected IPH and TRFC are not related to the presence of old and recent cortical and subcortical infarcts ipsilateral to a symptomatic carotid artery stenosis of 30% to 69%. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01208025.

Intraplaque hemorrhage, fibrous cap status, and microembolic signals in symptomatic patients with mild to moderate carotid artery stenosis: the Plaque at RISK study.

BACKGROUND AND PURPOSE: In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH. METHODS: In this multicenter, diagnostic cohort study, patients with recent transient ischemic attack or minor stroke in the carotid territory and an ipsilateral mild to moderate carotid artery plaque were included. IPH and FC status were dichotomously scored. Analysis of transcranial Doppler data was done blinded for the MRI results. Differences between groups were analyzed with Fisher exact test. RESULTS: A total of 113 patients were included. Transcranial Doppler measurements were feasible in 105 patients (average recording time, 219 minutes). A total of 26 MESs were detected in 8 of 105 patients. In 44 of 105 plaques IPH was present. In 92 of 105 plaques FC status was assessable, 36 of these had a thin/ruptured FC. No significant difference in the prevalence of MES between patients with and without IPH (P=0.46) or with thick versus thin/ruptured FC (P=0.48) was found. CONCLUSIONS: In patients with a symptomatic mild to moderate carotid artery stenosis, IPH and FC status are not associated with MES. This suggests that MRI and transcranial Doppler provide different information on plaque vulnerability. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709045.

Numerical simulations of carotid MRI quantify the accuracy in measuring atherosclerotic plaque components in vivo.

PURPOSE: Atherosclerotic carotid plaques can be quantified in vivo by MRI. However, the accuracy in segmentation and quantification of components such as the thin fibrous cap (FC) and lipid-rich necrotic core (LRNC) remains unknown due to the lack of a submillimeter scale ground truth. METHODS: A novel approach was taken by numerically simulating in vivo carotid MRI providing a ground truth comparison. Upon evaluation of a simulated clinical protocol, MR readers segmented simulated images of cross-sectional plaque geometries derived from histological data of 12 patients. RESULTS: MR readers showed high correlation (R) and intraclass correlation (ICC) in measuring the luminal area (R = 0.996, ICC = 0.99), vessel wall area (R = 0.96, ICC = 0.94) and LRNC area (R = 0.95, ICC = 0.94). LRNC area was underestimated (mean error, -24%). Minimum FC thickness showed a mediocre correlation and intraclass correlation (R = 0.71, ICC = 0.69). CONCLUSION: Current clinical MRI can quantify carotid plaques but shows limitations for thin FC thickness quantification. These limitations could influence the reliability of carotid MRI for assessing plaque rupture risk associated with FC thickness. Overall, MRI simulations provide a feasible methodology for assessing segmentation and quantification accuracy, as well as for improving scan protocol design.

The influence of inaccuracies in carotid MRI segmentation on atherosclerotic plaque stress computations.

Biomechanical finite element analysis (FEA) based on in vivo carotid magnetic resonance imaging (MRI) can be used to assess carotid plaque vulnerability noninvasively by computing peak cap stress. However, the accuracy of MRI plaque segmentation and the influence this has on FEA has remained unreported due to the lack of a reliable submillimeter ground truth. In this study, we quantify this influence using novel numerical simulations of carotid MRI. Histological sections from carotid plaques from 12 patients were used to create 33 ground truth plaque models. These models were subjected to numerical computer simulations of a currently used clinically applied 3.0 T T1-weighted black-blood carotid MRI protocol (in-plane acquisition voxel size of 0.62 × 0.62 mm2) to generate simulated in vivo MR images from a known underlying ground truth. The simulated images were manually segmented by three MRI readers. FEA models based on the MRI segmentations were compared with the FEA models based on the ground truth. MRI-based FEA model peak cap stress was consistently underestimated, but still correlated (R) moderately with the ground truth stress: R = 0.71, R = 0.47, and R = 0.76 for the three MRI readers respectively (p < 0.01). Peak plaque stretch was underestimated as well. The peak cap stress in thick-cap, low stress plaques was substantially more accurately and precisely predicted (error of -12 ± 44 kPa) than the peak cap stress in plaques with caps thinner than the acquisition voxel size (error of -177 ± 168 kPa). For reliable MRI-based FEA to compute the peak cap stress of carotid plaques with thin caps, the current clinically used in-plane acquisition voxel size (∼0.6 mm) is inadequate. FEA plaque stress computations would be considerably more reliable if they would be used to identify thick-cap carotid plaques with low stresses instead.

Wall shear stress-related plaque growth of lipid-rich plaques in human coronary arteries: an near-infrared spectroscopy and optical coherence tomography study.

AIMS: Low wall shear stress (WSS) is acknowledged to play a role in plaque development through its influence on local endothelial function. Also, lipid-rich plaques (LRPs) are associated with endothelial dysfunction. However, little is known about the interplay between WSS and the presence of lipids with respect to plaque progression. Therefore, we aimed to study the differences in WSS-related plaque progression between LRPs, non-LRPs, or plaque-free regions in human coronary arteries. METHODS AND RESULTS: In the present single-centre, prospective study, 40 patients who presented with an acute coronary syndrome successfully underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) of at least one non-culprit vessel at baseline and completed a 1-year follow-up. WSS was computed applying computational fluid dynamics to a three-dimensional reconstruction of the coronary artery based on the fusion of the IVUS-segmented lumen with a CT-derived centreline, using invasive flow measurements as boundary conditions. For data analysis, each artery was divided into 1.5 mm/45° sectors. Plaque growth based on IVUS-derived percentage atheroma volume change was compared between LRPs, non-LRPs, and plaque-free wall segments, as assessed by both OCT and NIRS. Both NIRS- and OCT-detected lipid-rich sectors showed a significantly higher plaque progression than non-LRPs or plaque-free regions. Exposure to low WSS was associated with a higher plaque progression than exposure to mid or high WSS, even in the regions classified as a plaque-free wall. Furthermore, low WSS and the presence of lipids had a synergistic effect on plaque growth, resulting in the highest plaque progression in lipid-rich regions exposed to low shear stress. CONCLUSION: This study demonstrates that NIRS- and OCT-detected lipid-rich regions exposed to low WSS are subject to enhanced plaque growth over a 1-year follow-up. The presence of lipids and low WSS proves to have a synergistic effect on plaque growth.

Comparison of fundamental, second harmonic, and superharmonic imaging: a simulation study.

In medical ultrasound, fundamental imaging (FI) uses the reflected echoes from the same spectral band as that of the emitted pulse. The transmission frequency determines the trade-off between penetration depth and spatial resolution. Tissue harmonic imaging (THI) employs the second harmonic of the emitted frequency band to construct images. Recently, superharmonic imaging (SHI) has been introduced, which uses the third to the fifth (super) harmonics. The harmonic level is determined by two competing phenomena: nonlinear propagation and frequency dependent attenuation. Thus, the transmission frequency yielding the optimal trade-off between the spatial resolution and the penetration depth differs for THI and SHI. This paper quantitatively compares the concepts of fundamental, second harmonic, and superharmonic echocardiography at their optimal transmission frequencies. Forward propagation is modeled using a 3D-KZK implementation and the iterative nonlinear contrast source (INCS) method. Backpropagation is assumed to be linear. Results show that the fundamental lateral beamwidth is the narrowest at focus, while the superharmonic one is narrower outside the focus. The lateral superharmonic roll-off exceeds the fundamental and second harmonic roll-off. Also, the axial resolution of SHI exceeds that of FI and THI. The far-field pulse-echo superharmonic pressure is lower than that of the fundamental and second harmonic. SHI appears suited for echocardiography and is expected to improve its image quality at the cost of a slight reduction in depth-of-field.

The definition of low wall shear stress and its effect on plaque progression estimation in human coronary arteries.

Wall shear stress (WSS), the frictional force of the blood on the vessel wall, plays a crucial role in atherosclerotic plaque development. Low WSS has been associated with plaque growth, however previous research used different approaches to define low WSS to investigate its effect on plaque progression. In this study, we used four methodologies to allocate low, mid and high WSS in one dataset of human coronary arteries and investigated the predictive power of low WSS for plaque progression. Coronary reconstructions were based on multimodality imaging, using intravascular ultrasound and CT-imaging. Vessel-specific flow was measured using Doppler wire and computational fluid dynamics was performed to calculate WSS. The absolute WSS range varied greatly between the coronary arteries. On the population level, the established pattern of most plaque progression at low WSS was apparent in all methodologies defining the WSS categories. However, for the individual patient, when using measured flow to determine WSS, the absolute WSS values range so widely, that the use of absolute thresholds to determine low WSS was not appropriate to identify regions at high risk for plaque progression.

Morphometric and Mechanical Analyses of Calcifications and Fibrous Plaque Tissue in Carotid Arteries for Plaque Rupture Risk Assessment.

OBJECTIVE: Atherosclerotic plaque rupture in carotid arteries is a major source of cerebrovascular events. Calcifications are highly prevalent in carotid plaques, but their role in plaque rupture remains poorly understood. This work studied the morphometric features of calcifications in carotid plaques and their effect on the stress distribution in the fibrous plaque tissue at the calcification interface, as a potential source of plaque rupture and clinical events. METHODS: A comprehensive morphometric analysis of 65 histology cross-sections from 16 carotid plaques was performed to identify the morphology (size and shape) and location of plaque calcifications, and the fibrous tissue fiber organization around them. Calcification-specific finite element models were constructed to examine the fibrous plaque tissue stresses at the calcification interface. Statistical correlation analysis was performed to elucidate the impact of calcification morphology and fibrous tissue organization on interface stresses. RESULTS: Hundred-seventy-one calcifications were identified on the histology cross-sections, which showed great variation in morphology. Four distinct patterns of fiber organization in the plaque tissue were observed around the calcification. They were termed as attached, pushed-aside, encircling and random patterns. The stress analyses showed that calcifications are correlated with high interface stresses, which might be comparable to or even above the plaque strength. The stress levels depended on the calcification morphology and fiber organization. Thicker calcification with a circumferential slender shape, located close to the lumen were correlated most prominently to high interface stresses. CONCLUSION: Depending on its morphology and the fiber organization around it, a calcification in an atherosclerotic plaque can act as a stress riser and cause high interface stresses. SIGNIFICANCE: This study demonstrated the potential of calcifications in atherosclerotic plaques to cause elevated stresses in plaque tissue and provided a biomechanical explanation for the histopathological findings of calcification-associated plaque rupture.

Lipid-rich Plaques Detected by Near-infrared Spectroscopy Are More Frequently Exposed to High Shear Stress.

High wall shear stress (WSS) and near-infrared spectroscopy (NIRS) detected lipid-rich plaque (LRP) are both known to be associated with plaque destabilization and future adverse cardiovascular events. However, knowledge of spatial co-localization of LRP and high WSS is lacking. This study investigated the co-localization of LRP based on NIRS and high WSS. Fifty-three patients presenting acute coronary syndrome underwent NIRS-intravascular-ultrasound (NIRS-IVUS) imaging of a non-culprit coronary artery. WSS was obtained using WSS profiling in 3D-reconstructions of the coronary arteries based on fusion of IVUS-segmented lumen and CT-derived 3D-centerline. Thirty-eight vessels were available for final analysis and divided into 0.5 mm/45° sectors. LRP sectors, as identified by NIRS, were more often colocalized with high WSS than sectors without LRP. Moreover, there was a dose-dependent relationship between lipid content and high WSS exposure. This study is a first step in understanding the evolution of LRPs to vulnerable plaques. Graphical Abstract.

The Association Between Time-Varying Wall Shear Stress and the Development of Plaque Ulcerations in Carotid Arteries From the Plaque at Risk Study.

Background and Purpose: Shear stress (WSS) is involved in the pathophysiology of atherosclerotic disease and might affect plaque ulceration. In this case-control study, we compared carotid plaques that developed a new ulcer during follow-up and plaques that remained silent for their exposure to time-dependent oscillatory shear stress parameters at baseline. Materials and Methods: Eighteen patients who underwent CTA and MRI of their carotid arteries at baseline and 2 years follow-up were included. These 18 patients consisted of six patients who demonstrated a new ulcer and 12 control patients selected from a larger cohort with similar MRI-based plaque characteristics as the ulcer group. (Oscillatory) WSS parameters [time average WSS, oscillatory shear index (OSI), and relative residence time (RRT)] were calculated using computational fluid dynamics applying the MRI-based geometry of the carotid arteries and compared among plaques (wall thickness>2 mm) with and without ulceration (Mann-Whitney U test) and ulcer-site vs. non-ulcer-site within the plaque (Wilcoxon signed rank test). More detailed analysis on ulcer cases was performed and the predictive value of oscillatory WSS parameters was calculated using linear and logistic mixed-effect regression models. Results: The ulcer group demonstrated no difference in maximum WSS [9.9 (6.6-18.5) vs. 13.6 (9.7-17.7) Pa, p = 0.349], a lower maximum OSI [0.04 (0.01-0.10) vs. 0.12 (0.06-0.20) p = 0.019] and lower maximum RRT [1.25 (0.78-2.03) Pa-1 vs. 2.93 (2.03-5.28) Pa-1, p = 0.011] compared to controls. The location of the ulcer (ulcer-site) within the plaque was not always at the maximal WSS, but demonstrated higher average WSS, lower average RRT and OSI at the ulcer-site compared to the non-ulcer-sites. High WSS (WSS>4.3 Pa) and low RRT (RRT < 0.25 Pa) were associated with ulceration with an odds ratio of 3.6 [CI 2.1-6.3] and 2.6 [CI 1.54-4.44] respectively, which remained significant after adjustment for wall thickness. Conclusion: In this explorative study, ulcers were not exclusively located at plaque regions exposed to the highest WSS, OSI, or RRT, but high WSS and low RRT regions had a significantly higher odds to present ulceration within the plaque even after adjustment for wall thickness.

Rapamycin modulates the eNOS vs. shear stress relationship.

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 microg/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 p27kip1 expression 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 (>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.

Simulation of stent deployment in a realistic human coronary artery.

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.

No Association between Thrombin Generation and Intra-Plaque Haemorrhage in Symptomatic Carotid Atherosclerotic Plaques: The Plaque at RISK (PARISK) Study.

BACKGROUND: Carotid atherosclerosis is an important cause of stroke. Intra-plaque haemorrhage (IPH) on magnetic resonance imaging (MRI) increases stroke risk. Development of IPH is only partly understood. Thrombin is an essential enzyme in haemostasis. Experimental animal studies have shown conflicting results on the relation between thrombin and plaque vulnerability. We hypothesize that decreased thrombin generation (TG) is associated with IPH and plaque vulnerability. OBJECTIVE: This article investigates whether TG is associated with IPH and other features of plaque vulnerability in stroke patients. METHODS: Recently symptomatic stroke patients underwent carotid MRI and blood sampling. MRI plaque features include plaque burden, presence of IPH, amount of lipid-rich necrotic core (LRNC), calcified tissue and fibrous tissue (% of total wall volume). TG was assessed in platelet-poor plasma and expressed as: peak height (PH) and endogenous thrombin potential (ETP). MR images could be analysed in 224 patients. Blood samples were available in 161 of 224 patients. Binary multivariate logistic and linear regression were used to investigate the association between TG and MRI plaque features. RESULTS: IPH and LRNC were present in 65 (40%) and 102 (63%) of plaques. There were no significant associations between TG and IPH; PH odds ratio (OR) = 1, 95% confidence interval (CI): 0.76 to 1.45 and ETP OR = 1, 95% CI: 0.73 to 1.37. After correction for age, sex and hypercholesterolaemia, the association was weak but non-significant; PH: OR = 0.76, 95% CI: 0.52 to 1.10 and ETP: OR = 0.73, 95% CI: 0.53 to 1.37. CONCLUSION: Features of carotid plaque on MRI show no significant association with TG in stroke patients. Systemic TG does not seem to be an important factor in IPH development.

Plaque rupture in the carotid artery is localized at the high shear stress region: a case report.

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.

Robust intravascular optical coherence elastography by line correlations.

We present a new method for intravascular optical coherence elastography, which is robust against motion artefacts. It employs the correlation between adjacent lines, instead of subsequent frames. Pressure to deform the tissue is applied synchronously with the line scan rate of the optical coherence tomography (OCT) instrument. The viability of the method is demonstrated with a simulation study. We find that the root mean square (rms) error of the displacement estimate is 0.55 microm, and the rms error of the strain is 0.6%. It is shown that high-strain spots in the vessel wall, such as observed at the sites of vulnerable atherosclerotic lesions, can be detected with the technique.

Three-dimensional echocardiographic analysis of left ventricular function during hemodialysis.

BACKGROUND: The effects of hemodialysis (HD) on left ventricular (LV) function have been studied by various echocardiographic techniques (M-mode, 2D echocardiography). These studies are hampered by a low accuracy of measurements because of geometric assumptions regarding LV shape. Three-dimensional echocardiography (3DE) overcomes this limitation. METHODS: We tested the feasibility of 3DE assessment of LV function during HD. Conventional biplane Simpson rule (BSR) and single plane area length method (SPM) for LV function analysis were used as a reference. RESULTS: 12 HD patients were studied and in 10 (83%) a total of 80 3D datasets were acquired. In 3 patients, one dataset (4%) was of insufficient quality and excluded from analysis. Correlation between SPM, BSR and 3DE for calculation of end-diastolic (EDV, r = 0.89 and r = 0.92, respectively), end-systolic volume (ESV, r = 0.92 and r = 0.93, respectively) and for ejection fraction (EF, r = 0.90 and r = 0.88, respectively) was moderate. Limits-of-agreement results for EDV and ESV were poor with confidence intervals larger than 30 ml. Both 2DE methods underestimated end-diastolic and end-systolic volume, while overestimating ejection fraction. CONCLUSION: 3DE is feasible for image acquisition during HD, which opens the possibility for accurate and reproducible measurement of LV function during HD. This may improve the assessment of the acute effect of HD on LV performance, and guide therapeutic strategies aimed at preventing intradialytic hypotension.