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.

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.

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.

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.

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.

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.

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.

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.

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.

The effects of plaque morphology and material properties on peak cap stress in human coronary arteries.

Heart attacks are often caused by rupture of caps of atherosclerotic plaques in coronary arteries. Cap rupture occurs when cap stress exceeds cap strength. We investigated the effects of plaque morphology and material properties on cap stress. Histological data from 77 coronary lesions were obtained and segmented. In these patient-specific cross sections, peak cap stresses were computed by using finite element analyses. The finite element analyses were 2D, assumed isotropic material behavior, and ignored residual stresses. To represent the wide spread in material properties, we applied soft and stiff material models for the intima. Measures of geometric plaque features for all lesions were determined and their relations to peak cap stress were examined using regression analyses. Patient-specific geometrical plaque features greatly influence peak cap stresses. Especially, local irregularities in lumen and necrotic core shape as well as a thin intima layer near the shoulder of the plaque induce local stress maxima. For stiff models, cap stress increased with decreasing cap thickness and increasing lumen radius (R = 0.79). For soft models, this relationship changed: increasing lumen radius and increasing lumen curvature were associated with increased cap stress (R = 0.66). The results of this study imply that not only accurate assessment of plaque geometry, but also of intima properties is essential for cap stress analyses in atherosclerotic plaques in human coronary arteries.

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.

Measuring submicrometer displacement vectors using high-frame-rate ultrasound imaging.

Measuring the magnitude and direction of tissue displacement provides the basis for the assessment of tissue motion or tissue stiffness. Using conventional displacement tracking by ultrasound delay estimation, only one direction of tissue displacement can be estimated reliably. In this paper, we describe a new technique for estimating the complete two-dimensional displacement vector using high-frame-rate ultrasound imaging. We compute the displacement vector using phase delays that can be measured between pairs of elements within an array. By combining multiple element-pair solutions, we find a new robust estimate for the displacement vector. In this paper, we provide experimental proof that this method permits measurement of the displacement vector for isolated scatterers and diffuse scatterers with high (submicrometer) precision, without the need for beam steering. We also show that we can measure the axial and lateral distension of a carotid artery in a transverse view.

A computer-simulation study on the effects of MRI voxel dimensions on carotid plaque lipid-core and fibrous cap segmentation and stress modeling.

BACKGROUND: The benefits of a decreased slice thickness and/or in-plane voxel size in carotid MRI for atherosclerotic plaque component quantification accuracy and biomechanical peak cap stress analysis have not yet been investigated in detail because of practical limitations. METHODS: In order to provide a methodology that allows such an investigation in detail, numerical simulations of a T1-weighted, contrast-enhanced, 2D MRI sequence were employed. Both the slice thickness (2 mm, 1 mm, and 0.5 mm) and the in plane acquired voxel size (0.62x0.62 mm2 and 0.31x0.31 mm2) were varied. This virtual MRI approach was applied to 8 histology-based 3D patient carotid atherosclerotic plaque models. RESULTS: A decreased slice thickness did not result in major improvements in lumen, vessel wall, and lipid-rich necrotic core size measurements. At 0.62x0.62 mm2 in-plane, only a 0.5 mm slice thickness resulted in improved minimum fibrous cap thickness measurements (a 2-3 fold reduction in measurement error) and only marginally improved peak cap stress computations. Acquiring voxels of 0.31x0.31 mm2 in-plane, however, led to either similar or significantly larger improvements in plaque component quantification and computed peak cap stress. CONCLUSIONS: This study provides evidence that for currently-used 2D carotid MRI protocols, a decreased slice thickness might not be more beneficial for plaque measurement accuracy than a decreased in-plane voxel size. The MRI simulations performed indicate that not a reduced slice thickness (i.e. more isotropic imaging), but the acquisition of anisotropic voxels with a relatively smaller in-plane voxel size could improve carotid plaque quantification and computed peak cap stress accuracy.

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.

Fast and accurate pressure-drop prediction in straightened atherosclerotic coronary arteries.

Atherosclerotic disease progression in coronary arteries is influenced by wall shear stress. To compute patient-specific wall shear stress, computational fluid dynamics (CFD) is required. In this study we propose a method for computing the pressure-drop in regions proximal and distal to a plaque, which can serve as a boundary condition in CFD. As a first step towards exploring the proposed method we investigated ten straightened coronary arteries. First, the flow fields were calculated with CFD and velocity profiles were fitted on the results. Second, the Navier-Stokes equation was simplified and solved with the found velocity profiles to obtain a pressure-drop estimate (Δp (1)). Next, Δp (1) was compared to the pressure-drop from CFD (Δp CFD) as a validation step. Finally, the velocity profiles, and thus the pressure-drop were predicted based on geometry and flow, resulting in Δp geom. We found that Δp (1) adequately estimated Δp CFD with velocity profiles that have one free parameter ß. This ß was successfully related to geometry and flow, resulting in an excellent agreement between Δp CFD and Δp geom: 3.9 ± 4.9% difference at Re = 150. We showed that this method can quickly and accurately predict pressure-drop on the basis of geometry and flow in straightened coronary arteries that are mildly diseased.

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.

Atherosclerotic plaque fibrous cap assessment under an oblique scan plane orientation in carotid MRI.

Carotid magnetic resonance imaging (MRI) is used to noninvasively assess atherosclerotic plaque fibrous cap (FC) status, which is closely related to ischemic stroke. Acquiring anisotropic voxels improves in-plane visualization, however, an oblique scan plane orientation could then obscure a FC (i.e., contrast below the noise level) and thus impair a reliable status assessment. To quantify this, we performed single-slice numerical simulations of a clinical 3.0T, 2D T1-weighted, black-blood, contrast-enhanced pulse sequence with various voxel dimensions: in-plane voxel size of 0.62 mm × 0.62 mm and 0.31 mm × 0.31 mm, slice thickness of 1, 2, and 3 mm. Idealized plaque models (FC thickness of 0.5, 1, and 1.5 mm) were imaged at various scan plane angles (0°-40° in steps of 10°), and the FC contrast was quantified. We found that when imaging thin FCs with anisotropic voxels, the FC contrast decreased when the scan plane orientation angle increased. However, a reduced in-plane voxel size at the cost of an increased slice thickness often led to enhanced FC contrast even in the presence of scan plane orientation angles of up to 40°. It can be concluded that while isotropic-voxel imaging eliminates the issue of scan plane obliqueness, it comes at the cost of reduced FC contrast, thus likely decreasing the reliability of FC status assessment in carotid MRI. If scan plane orientation obliquity at the slice of interest is moderate (<40°) or otherwise diminished through careful scan planning, voxel anisotropy could increase FC contrast and, in effect, increase the reliability of FC status assessment.

High-definition imaging of carotid artery wall dynamics.

The carotid artery (CA) is central to cardiovascular research, because of the clinical relevance of CA plaques as culprits of stroke and the accessibility of the CA for cardiovascular screening. The viscoelastic state of this artery, essential for clinical evaluation, can be assessed by observing arterial deformation in response to the pressure changes throughout the cardiac cycle. Ultrasound imaging has proven to be an excellent tool to monitor these dynamic deformation processes. We describe how a new technique called high-frame-rate ultrasound imaging captures the tissue deformation dynamics throughout the cardiac cycle in unprecedented detail. Local tissue motion exhibits distinct features of sub-micrometer displacements on a sub-millisecond time scale. We present a high-definition motion analysis technique based on plane wave ultrasound imaging able to capture these features. We validated this method by screening a group of healthy volunteers and compared the results with those for two patients known to have atherosclerosis to illustrate the potential utility of this technique.

3D reconstruction techniques of human coronary bifurcations for shear stress computations.

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.