Change in Carotid Intraplaque Hemorrhage in Community-dwelling Subjects: A Follow-up Study Using Serial MR Imaging.

Purpose To investigate intraplaque hemorrhage (IPH) development and change over time. Materials and Methods Institutional review board approval and written informed consent from all participants were obtained. From a population-based study on subclinical atherosclerosis, 40 participants with IPH at baseline magnetic resonance (MR) imaging (53 carotids with IPH) were randomly selected and were matched with 27 control subjects (53 carotids without IPH) to undergo a second MR examination (mean interval, 17 months ± 4 [standard deviation]) to assess IPH change. IPH volume change was evaluated by using both a visual rating scale and an automated volumetric segmentation tool. Cardiovascular risk factors for IPH volume change were investigated with linear regression analyses. Results IPH remained present in 50 (94%) of the 53 carotids with IPH at baseline, and it developed in five (7%) of the 40 carotids without IPH at baseline. Visual progression of IPH volume was present in 14 (26%) of the 53 carotids with IPH at baseline, and regression was present in 16 (30%). Mean quantitative change in IPH volume was -13.7 mm3 ± 62.6 per year of follow-up. Male sex (men vs women, 37.7 mm3; 95% confidence interval [CI]: 11.0, 64.4; P = .006), smoking (smokers vs nonsmokers, 45.2 mm3; 95% CI: 7.1, 83.4; P = .020), and hypertension (subjects with hypertension vs those without hypertension, 32.5 mm3; 95% CI: 7.7, 57.2; P = .010) were associated with IPH volume change. Conclusion During 17 months of follow-up, both visual progression and regression of IPH volume occurs, whereas quantitatively IPH volume decreases. This suggests that IPH is a dynamic process with potential for either growth or resolution over time. © RSNA, 2016 Online supplemental material is available for this article.

Carotid Atherosclerotic Plaque Characteristics on Magnetic Resonance Imaging Relate With History of Stroke and Coronary Heart Disease.

BACKGROUND AND PURPOSE: Because atherosclerosis is a systemic disease, presence and composition on 1 location may relate to ischemic events in distant locations. We examined whether carotid atherosclerotic wall thickness, stenosis, and plaque composition are related to history of ischemic stroke and coronary heart disease (CHD). METHODS: From the population-based Rotterdam Study, 1731 asymptomatic participants (mean age, 72.4±9.1 years; 55% males) underwent magnetic resonance imaging of both carotid arteries. We assessed carotid wall thickness, stenosis and plaque composition, that is presence of intraplaque hemorrhage, lipid, and calcification. History of ischemic stroke and CHD was assessed until date of magnetic resonance imaging. The study was approved by the institutional review board, and all participants gave informed consent. Logistic regression analyses adjusted for age and traditional cardiovascular risk factors were used to study sex-specific associations between plaque characteristics and clinical events. RESULTS: We found that both carotid stenosis and intraplaque hemorrhage were associated with ischemic stroke in men but not in women (men: odds ratio [OR] for stenosis [per 10% increase]: 1.17 [95% CI, 1.06-1.30] and for intraplaque hemorrhage 2.39 [95% CI, 1.32-4.35]). In both men and women, carotid stenosis was associated with CHD (men: OR per 10% increase 1.12 [95% CI, 1.04-1.21] and women: OR, 1.17 [95% CI, 1.03-1.34]) and carotid wall thickness was associated with CHD (men: OR, 1.20 [95% CI, 1.03-1.39] and women: OR, 1.21 [95% CI, 0.88-1.65]). None of the plaque components was associated with CHD. CONCLUSIONS: Whereas carotid plaque thickness and stenosis are associated with the history of ischemic stroke and CHD, carotid intraplaque hemorrhage is associated with ischemic stroke, but not with CHD, providing novel insights into the pathogenesis of cardiovascular events.

Right ventricular strain by MR quantitatively identifies regional dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Analysis of regional wall motion of the right ventricle (RV) is primarily qualitative with large interobserver variation in clinical practice. Thus, the purpose of this study was to use feature tracking to analyze regional wall motion abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: We enrolled 110 subjects (39 overt ARVC [mutation+/phenotype+] (35.5%), 40 preclinical ARVC [mutation+/phenotype-] (36.3%), and 31 control subjects (28.2%)). Cine steady state free precession cardiac MR was performed with temporal resolution ≤40 ms in the horizontal long axis (HLA), axial, and short axis directions. Regional strain was analyzed using feature tracking software and reproducibility was assessed by means of intraclass correlation coefficient. Dunnett's test was used in univariate analysis for comparisons to control subjects; cumulative odds logistic regression was used for minimally and fully adjusted multivariate models. RESULTS: Strain was significantly impaired in overt ARVC compared with control subjects both globally (P < 0.01) and regionally (all segments of HLA view, P < 0.01). In the HLA view, regional reproducibility was excellent within (intraclass correlation coefficient [ICC] = 0.81) and moderate between (ICC = 0.62) observers. Using a threshold of -31% subtricuspid strain in the HLA view, the sensitivity and specificity for overt ARVC were 75.0% and 78.2%, respectively. In multivariable analysis involving all three groups, subtricuspid strain less than -31% (beta = 1.38; P = 0.014) and RV end diastolic volume index (beta = 0.06; P = 0.001) were significant predictors of disease presence. CONCLUSION: RV strain can be reproducibly assessed with MR feature tracking, and regional strain is abnormal in overt ARVC compared with control subjects.

Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis.

AIMS: Cholesterol efflux capacity (CEC) was recently shown to predict future cardiovascular (CV) events. Psoriasis both increases CV risk and impairs CEC. However, whether having poor CEC is associated with coronary plaque burden is currently unknown. We aimed to assess the cross-sectional relationship between coronary plaque burden assessed by quantitative coronary computed tomography angiography (CCTA) with CEC in a well-phenotyped psoriasis cohort. METHODS AND RESULTS: Total burden and non-calcified burden (NCB) plaque indices were assessed in 101 consecutive psoriasis patients using quantitative software. Cholesterol efflux capacity was quantified using a cell-based ex vivo assay measuring the ability of apoB-depleted plasma to mobilize cholesterol from lipid-loaded macrophages. Cholesterol efflux capacity was inversely correlated with NCB (unadjusted ß-coefficient -0.33; P < 0.001), and this relationship persisted after adjustment for CV risk factors (ß -0.24; P < 0.001), HDL-C levels (ß -0.22; P < 0.001), and apoA1 levels (ß -0.19; P < 0.001). Finally, we observed a significant gender interaction (P < 0.001) whereby women with low CEC had higher NCB compared to men with low CEC. CONCLUSIONS: We show that CEC is inversely associated with prevalent coronary plaque burden measured by quantitative CCTA. Low CEC may therefore be an important biomarker for subclinical coronary atherosclerosis in psoriasis. CLINICALTRIALSGOV: NCT01778569.

Left-sided strokes are more often recognized than right-sided strokes: the Rotterdam study.

BACKGROUND AND PURPOSE: Left-sided strokes are reported to be more common than right-sided strokes, but it is unknown whether they occur more often or are simply recognized more easily by clinicians. In a large unselected community-dwelling population, we examined the frequency of clinical left- and right-sided strokes and transient ischemic attacks (TIAs) and compared it with the frequency of left- and right-sided infarcts on MRI. METHODS: This study was conducted within the population-based Rotterdam Study. Between 1990 and 2012, 13 894 participants were followed up for first-ever stroke and TIA. MRI scans were performed within a random subgroup of 5081 persons and were rated for the presence of supratentorial cortical and lacunar infarcts. We compared frequencies of left- and right-sided strokes, TIAs, or MRI infarcts using binomial and Fisher exact tests. RESULTS: After a mean follow-up of 9.6 (±6.0) years, 1252 patients had a stroke, of which 704 were ischemic, and 799 participants had a TIA. Within the subgroup with MRI, we identified 673 infarcts. Ischemic strokes were more frequently left-sided (57.7%; 95% confidence interval, 53.7-61.6) than right-sided, similar to TIAs (57.8% left-sided; 53.4-62.3). In contrast, we found no left-right difference in distribution of infarcts on MRI (51.9% left-sided; 48.1-55.6). CONCLUSIONS: Clinical ischemic strokes and TIAs are more frequently left-sided than right-sided, whereas this difference is not present for infarcts on MRI. This suggests that left-sided strokes and TIAs are more easily recognized. Consequently, there should be more attention for symptoms of right-sided strokes and TIAs.

Arterial stiffness is associated with carotid intraplaque hemorrhage in the general population: the Rotterdam study.

OBJECTIVE: The relation between arterial stiffness and atherosclerosis, and specifically the influence of arterial stiffness on plaque composition, is largely unknown. In a population-based study, we investigated the association between arterial stiffness and the presence and composition of carotid atherosclerotic plaques. APPROACH AND RESULTS: Arterial stiffness was measured in 6527 participants (67.0±8.6 years) using aortic pulse wave velocity (PWV). Presence of carotid atherosclerotic plaques was assessed with ultrasound. Subsequently, 1059 subjects with carotid plaques (>2.5 mm) underwent MRI to assess plaque composition (presence of intraplaque hemorrhage, lipid, and calcification). Generalized estimation equation analyses adjusted for age, sex, mean arterial pressure, heart rate, carotid wall thickening, pulse pressure, and traditional cardiovascular risk factors were used to study the association between PWV and the presence and composition of carotid atherosclerotic plaques. In multivariable analysis, higher PWV was independently related to higher prevalence of carotid atherosclerotic plaque on ultrasound (odds ratio for highest quartile of PWV compared with lowest quartile, 1.24 [95% confidence interval, 1.02-1.51]). Furthermore, higher PWV was associated with intraplaque hemorrhage (age- and sex-adjusted odds ratio per SD increase in PWV, 1.20 [1.04-1.38] and calcification, 1.18 [1.03-1.35]), but not with lipid. After adjustment for cardiovascular risk factors, PWV remained significantly associated with intraplaque hemorrhage (1.20 [1.01-1.43]). Additional adjustment for pulse pressure did not materially affect the effect estimate (1.19 [1.00-1.42]). CONCLUSIONS: Higher PWV is associated with presence and composition of carotid atherosclerotic plaques, in particular with intraplaque hemorrhage. These findings provide further clues for understanding the development of vulnerable atherosclerotic plaque.

Atherosclerotic plaque in the left carotid artery is more vulnerable than in the right.

BACKGROUND AND PURPOSE: Ischemic stroke is more often diagnosed in the left hemisphere than in the right. It is unknown whether this asymmetrical prevalence relates to differences in carotid atherosclerosis. We compared atherosclerotic plaque prevalence, severity, and composition between left and right carotid arteries. METHODS: In a population-based cohort, carotid MRI scanning was performed in 1414 stroke-free participants (≥45 years). Using a multisequence MRI protocol, we assessed the prevalence, stenosis, and thickness of the plaque and its predominant component (ie, lipid core, intraplaque hemorrhage, calcification, or fibrous tissue in each carotid artery). Differences between left and right side were tested using paired t tests, McNemar test and Generalized Estimating Equation analyses. RESULTS: The majority (85%) of the participants had bilateral carotid plaques. Unilateral plaques were twice more prevalent on the left than on the right side (67% versus 33%; P<0.001). Plaque thickness was also greater on the left (3.1±1.2 versus 2.9±1.3 mm; P<0.001); degree of stenosis did not differ. Intraplaque hemorrhage and fibrous tissue were more prevalent on the left (9.1 versus 5.9%; P<0.001 and 45.0 versus 38.5%; P<0.001), whereas calcification occurred more often on the right (37.4 versus 31.6% at the left; P<0.001). Lipid was equally distributed. CONCLUSIONS: Carotid atherosclerotic plaque size and composition are not symmetrically distributed. Predominance of intraplaque hemorrhage in left-sided carotid plaques suggests a greater vulnerability as opposed to right-sided plaques, which are more calcified and therefore considered more stable.

Atherosclerotic Carotid Plaque Composition and Incident Stroke and Coronary Events.

BACKGROUND: Increasing evidence suggests that atherosclerotic plaque composition rather than plaque size is linked to ischemic cardiovascular events, yet largescale population-based data in asymptomatic individuals remain scarce. OBJECTIVES: This study sought to investigate carotid plaque composition in relation to incident stroke and coronary heart disease (CHD) in a population-based setting. METHODS: Between 2007 and 2012, 1,349 persons (mean age 72 years, 49.5% women) from the population-based Rotterdam Study who were free from a history of stroke or CHD, in whom carotid ultrasonography showed subclinical atherosclerosis, and who underwent high-resolution magnetic resonance imaging of the carotid arteries to assess plaque characteristics. These included the presence of specific plaque components (intraplaque hemorrhage [IPH], lipid-rich necrotic core, and calcification), and measures of plaque size (maximum plaque thickness and presence of stenosis of more than 30%). Individuals were continuously followed for the occurrence of stroke or CHD until January 1, 2015. The authors used Cox regression models to assess the association of the plaque characteristics with the incidence of stroke and CHD, with adjustments for age, sex, and cardiovascular risk factors. RESULTS: During a median of 5.1 years' follow-up for stroke and 4.8 years for CHD, 51 individuals had a stroke and 83 developed CHD. Independent of maximum plaque thickness and cardiovascular risk factors, the presence of IPH was associated with incident stroke and CHD (fully adjusted hazard ratio: 2.42 [95% confidence interval: 1.30 to 4.50], and 1.95 [95% confidence interval: 1.20 to 3.14]). Presence of a lipid-rich necrotic core and calcification were not associated with stroke or CHD. CONCLUSIONS: The presence of IPH in the carotid atherosclerotic plaque is an independent risk factor for stroke and CHD. These findings indicate the promise of IPH as a marker of plaque vulnerability in healthy persons with subclinical atherosclerosis.

Serial noninvasive assessment of apoptosis during right ventricular disease progression in rats.

UNLABELLED: Right ventricular (RV) function is the major determinant of survival in patients with pulmonary hypertension. Yet, the pathophysiologic basis of RV disease is unresolved. We aimed to study the role of apoptosis in RV disease by monitoring it serially during disease progression using in vivo (99m)Tc-annexin-V ((99m)Tc-annexin) scintigraphy and study whether the reduction in apoptosis resulting from chronic treatment with valsartan can be detected by (99m)Tc-annexin scintigraphy. METHODS: RV disease after pulmonary hypertension was induced by monocrotaline injection in rats. The following 3 groups were studied: rats treated with monocrotaline (monocrotaline rats), rats treated with monocrotaline plus valsartan (valsartan rats), and age-matched controls (control rats). Serial echocardiography and in vivo (99m)Tc-annexin scintigraphy were performed. Apoptosis was confirmed by (99m)Tc-annexin autoradiography and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling. Fibrosis was assessed by picrosirius red staining. RESULTS: In monocrotaline rats, in vivo (99m)Tc-annexin uptake peaked early and declined thereafter but remained elevated, compared with baseline. These stage-dependent changes of in vivo (99m)Tc-annexin uptake were paralleled by changes in autoradiography and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling. Valsartan rats had longer RV failure-free survival than did monocrotaline rats and had reduced apoptosis. These changes were accompanied by commensurate delays in RV hypertrophy and RV dilation. Valsartan rats also had less fibrosis than monocrotaline rats at all disease stages. CONCLUSION: RV disease progression is associated with an early increase in RV apoptosis, as monitored using serial in vivo (99m)Tc-annexin scintigraphy. Delay in RV disease progression by valsartan is accompanied by reduction in RV apoptosis. Apoptosis plays a role in RV disease progression and may be assessed by serial in vivo (99m)Tc-annexin scintigraphy.

Change in Carotid Plaque Components: A 4-Year Follow-Up Study With Serial MR Imaging.

OBJECTIVES: The goal of this study was to determine how carotid plaque components (e.g., intraplaque hemorrhage [IPH], calcification, lipid core) change over time and which cardiovascular risk factors are associated with the development of each component. BACKGROUND: Carotid atherosclerotic plaque components are important markers of plaque vulnerability. How these components change and which factors lead to the development and changes in the components remain unclear. METHODS: A total of 198 participants (mean age 67.5 ± 10.6 years) from the population-based Rotterdam Study, all with carotid wall thickening on ultrasound, underwent 2 magnetic resonance imaging scans for carotid plaque characterization (mean interscan interval 4.1 ± 0.2 years). Presence of IPH, calcification, and lipid-rich necrotic core was assessed on both sides on the baseline and follow-up scans. The association between cardiovascular risk factors and incident carotid plaque components was assessed. RESULTS: In the 396 arteries, all plaque components significantly changed over time. Incidence of IPH, calcification, and lipid core was, respectively, 18.5%, 59.2%, and 39.6%. The factor most strongly associated with the incidence of IPH was use of antihypertensive drugs (multivariate adjusted odds ratio [OR]: 3.87; 95% confidence interval [CI]: 1.90 to 7.90) and severe hypertension (multivariate adjusted OR: 4.70; 95% CI: 1.50 to 14.80). The incidence of calcification was associated with hypertension (OR: 2.20; 95% CI: 1.07 to 4.40). Higher cholesterol levels were associated with incidence of lipid cores (multivariate adjusted OR per unit increase in cholesterol: 1.40; 95% CI: 1.10 to 1.70). CONCLUSIONS: In these community-dwelling subjects, characteristics of plaque composition changed dramatically within a few years, and cardiovascular risk factors played a major role in these changes. Hypertension and its treatment and serum cholesterol levels were the main risk factors for the development of atherosclerotic plaque components over time.

Statin use is associated with carotid plaque composition: The Rotterdam Study.

BACKGROUND: Statins represent a key treatment for cardiovascular disease. Nevertheless, the direct effects of statin treatment on the composition of atherosclerotic plaques remain elusive. OBJECTIVES: We aimed to investigate the association of statin treatment with the presence of different plaque components located in the carotid arteries within a population-based setting. METHODS: From the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis (mean age 72.9 years, 46% women) underwent MRI of the carotid arteries to determine the presence of calcification, lipid core, and intraplaque hemorrhage. Information for the duration and dosage of statin use was obtained from pharmacy records for all participants. We used logistic regression models to study the association of statin use with the presence of plaque components. RESULTS: Statin treatment was associated with a higher presence of calcification (OR: 1.73 [95% CI: 1.22-2.44]). Longer duration of use strengthened this association (OR: 1.82 [95% CI: 1.00-3.33] for 10 to 48 months, and OR 1.74 [95% CI: 1.09-2.77] for >48 months, compared to OR: 1.65 [95% CI: 0.94-2.89] for ≤10 months). Current statin treatment was also associated with a lower presence of lipid core (OR: 0.66 [95% CI: 0.42-1.04]), but only when using statins for 10 months or less. Any dosage of statins was associated with a higher presence of calcification, whilst only high dosages (DDD > 1.33) were associated with a lower presence of lipid core. CONCLUSIONS: Active, high-dosage statin use seems to beneficially influence the composition of carotid atherosclerosis by shifting the composition from vulnerable plaque with a lipid core to more stable calcified plaque.

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials.

INTRODUCTION: 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake in the artery wall correlates with active inflammation. However, in part due to the low spatial resolution of PET, variation in the apparent arterial wall signal may be influenced by variation in blood FDG activity that cannot be fully corrected for using typical normalization strategies. The purpose of this study was to evaluate the ability of the current common methods to normalize for blood activity and to investigate alternative methods for more accurate quantification of vascular inflammation. MATERIALS AND METHODS: The relationship between maximum FDG aorta wall activity and mean blood activity was evaluated in 37 prospectively enrolled subjects aged 55 years or more, treated for hyperlipidemia. Target maximum aorta standardized uptake value (SUV) and mean background reference tissue activity (blood, spleen, liver) were recorded. Target-to-background ratios (TBR) and arterial maximum activity minus blood activity were calculated. Multivariable regression was conducted, predicting uptake values based on variation in background reference and target tissue FDG uptake; adjusting for gender, age, lean body mass (LBM), blood glucose, blood pool activity, and glomerular filtration rate (GFR), where appropriate. RESULTS: Blood pool activity was positively associated with maximum artery wall SUV (ß = 5.61, P<0.0001) as well as mean liver (ß = 6.23, P<0.0001) and spleen SUV (ß = 5.20, P<0.0001). Artery wall activity divided by blood activity (TBRBlood) or subtraction of blood activity did not remove the statistically significant relationship to blood activity. Blood pool activity was not related to TBRliver and TBRspleen (ß = -0.36, P = NS and ß = -0.58, P = NS, respectively). CONCLUSIONS: In otherwise healthy individuals treated for hyperlipidemia, blood FDG activity is associated with artery wall activity. However, variation in blood activity may mask artery wall signal reflective of inflammation, which requires normalization. Blood-based TBR and subtraction do not sufficiently adjust for blood activity. Warranting further investigation, background reference tissues with cellular uptake such as the liver and spleen may better adjust for variation in blood activity to improve assessment of vascular activity.

Carotid Artery Wall Segmentation in Multispectral MRI by Coupled Optimal Surface Graph Cuts.

We present a new three-dimensional coupled optimal surface graph-cut algorithm to segment the wall of the carotid artery bifurcation from Magnetic Resonance (MR) images. The method combines the search for both inner and outer borders into a single graph cut and uses cost functions that integrate information from multiple sequences. Our approach requires manual localization of only three seed points indicating the start and end points of the segmentation in the internal, external, and common carotid artery. We performed a quantitative validation using images of 57 carotid arteries. Dice overlap of 0.86 ± 0.06 for the complete vessel and 0.89 ± 0.05 for the lumen compared to manual annotation were obtained. Reproducibility tests were performed in 60 scans acquired with an interval of 15 ± 9 days, showing good agreement between baseline and follow-up segmentations with intraclass correlations of 0.96 and 0.74 for the lumen and complete vessel volumes respectively.

High pitch third generation dual-source CT: Coronary and cardiac visualization on routine chest CT.

BACKGROUND: Chest CT scans are frequently performed in radiology departments but have not previously contained detailed depiction of cardiac structures. OBJECTIVES: To evaluate myocardial and coronary visualization on high-pitch non-gated CT of the chest using 3rd generation dual-source computed tomography (CT). METHODS: Cardiac anatomy of patients who had 3rd generation, non-gated high pitch contrast enhanced chest CT and who also had prior conventional (low pitch) chest CT as part of a chest abdomen pelvis exam was evaluated. Cardiac image features were scored by reviewers blinded to diagnosis and pitch. Paired analysis was performed. RESULTS: 3862 coronary segments and 2220 cardiac structures were evaluated by two readers in 222 CT scans. Most patients (97.2%) had chest CT for oncologic evaluation. The median pitch was 2.34 (IQR 2.05, 2.65) in high pitch and 0.8 (IQR 0.8, 0.8) in low pitch scans (p < 0.001). High pitch CT showed higher image visualization scores for all cardiovascular structures compared with conventional pitch scans (p < 0.0001). Coronary arteries were visualized in 9 coronary segments per exam in high pitch scans versus 2 segments for conventional pitch (p < 0.0001). Radiation exposure was lower in the high pitch group compared with the conventional pitch group (median CTDIvol 10.83 vs. 12.36 mGy and DLP 790 vs. 827 mGycm respectively, p < 0.01 for both) with comparable image noise (p = 0.43). CONCLUSION: Myocardial structure and coronary arteries are frequently visualized on non-gated 3rd generation chest CT. These results raise the question of whether the heart and coronary arteries should be routinely interpreted on routine chest CT that is otherwise obtained for non-cardiac indications.

Relation between wall shear stress and carotid artery wall thickening MRI versus CFD.

Wall shear stress (WSS), a parameter associated with endothelial function, is calculated by computational fluid dynamics (CFD) or phase-contrast (PC) MRI measurements. Although CFD is common in WSS (WSSCFD) calculations, PC-MRI-based WSS (WSSMRI) is more favorable in population studies; since it is straightforward and less time consuming. However, it is not clear if WSSMRI and WSSCFD show similar associations with vascular pathology. Our aim was to test the associations between wall thickness (WT) of the carotid arteries and WSSMRI and WSSCFD. The subjects (n=14) with an asymptomatic carotid plaque who underwent MRI scans two times within 4 years of time were selected from the Rotterdam Study. We compared WSSCFD and WSSMRI at baseline and follow-up. Baseline WSSMRI and WSSCFD values were divided into 3 categories representing low, medium and high WSS tertiles. WT of each tertile was compared by a one-way ANOVA test. The WSSMRI and WSSCFD were 0.50±0.13Pa and 0.73±0.25Pa at baseline. Although WSSMRI was underestimated, a significant regression was found between WSSMRI and WSSCFD (r(2)=0.71). No significant difference was found between baseline and follow-up WSS by CFD and MRI-based calculations. The WT at baseline was 1.36±0.16mm and did not change over time. The WT was 1.55±0.21mm in low, 1.33±0.20mm in medium and 1.21±0.21mm in the high WSSMRI tertiles. Similarly, the WT was 1.49±0.21mm in low, 1.33±0.20mm in medium and 1.26±0.21mm in high WSSCFD tertiles. We found that WSSMRI and WSSCFD were inversely related with WT. WSSMRI and WSSCFD patterns were similar although MRI-based calculations underestimated WSS.

Determinants of carotid atherosclerotic plaque burden in a stroke-free population.

BACKGROUND AND AIMS: In a large stroke-free population, we sought to identify cardiovascular risk factors and carotid plaque components associated with carotid plaque burden, lumen volume and stenosis. METHODS: The carotid arteries of 1562 stroke-free participants from The Rotterdam Study were imaged on a 1.5-Tesla MRI scanner. Inner and outer wall of the carotid arteries were automatically segmented and lumen volume (mm3), wall volume (outer wall-inner wall) and plaque burden (wall volume/outer wall volume) (%) were quantified. Plaque components were visually determined and luminal stenosis was assessed. We analyzed associations of cardiovascular risk factors and carotid plaque components with plaque burden and lumen volumes using regression analysis. RESULTS: We investigated 2821 carotid plaques and found that women had larger plaque burden (50.7 ± 7.8% vs. 49.2 ± 7.7%, p < 0.0001) and smaller lumen volumes (933 ± 286 mm3vs. 1078 ± 334 mm3, p < 0.0001) than men. In women, age, HDL-cholesterol and systolic blood pressure, and in men, total cholesterol, non-HDL cholesterol and statin use were independently associated with higher plaque burden and lumen volume. Furthermore, smoking and diabetes were associated with lumen volume in men (respectively p = 0.04 and p = 0.002). Intraplaque hemorrhage (IPH) and lipid were related to a larger plaque burden (OR 1.30 [1.05-1.60] and OR 1.28[1.06-1.55]). Finally, within the highest quartile of plaque burden, IPH was strongly associated with luminal stenosis independent of age, sex, plaque burden and composition (Beta = 15.2; [11.8-18.6]). CONCLUSIONS: Several cardiovascular risk factors and plaque components, in particular IPH, are associated with higher plaque burden. Carotid IPH is strongly associated with an increased luminal stenosis.

Semi-automatic MRI segmentation and volume quantification of intra-plaque hemorrhage.

PURPOSE: Intra-plaque hemorrhage (IPH) is associated with plaque instability. Therefore, the presence and volume of IPH in carotid arteries may be relevant in predicting the progression of atherosclerotic disease and the occurrence of clinical events. The aim of our work was to develop and evaluate a method for semi-automatic IPH segmentation in T1-weighted (T1w)-magnetic resonance imaging (MRI). MATERIAL AND METHODS: IPH segmentation is performed by a regional level set method that models the intensity of the IPH and the background in T1w-MRI to be smoothly varying. The method only requires minimal user interaction, i.e., one or more mouse clicks inside the hemorrhage serve as initialization. The parameters of the method are optimized using a leave-one-out strategy by maximizing the Dice similarity coefficient (DSC) between manual and semi-automatic segmentations. We evaluated the IPH segmentation method on 22 carotid arteries; 10 of which were annotated by two observers and 12 were scanned twice within a 2 week period. RESULTS: We obtained a DSC of 0.52 between the manual and level set segmentations on all 22 carotids. The inter-observer DSC on 10 arteries is 0.57, which is comparable to the DSC between the method and the manual segmentation (0.55). The correlation between the IPH volumes extracted from the level set segmentation and the manual segmentation is 0.88, which is close to the inter-observer volume correlation of 0.92. The reproducibility after rescanning 12 carotids yield an IPH volume correlation of 0.97. The robustness with respect to the initialization by manually clicking two sets of seed points in these 12 carotid artery pairs yields a volume correlation of 0.99. CONCLUSION: Semi-automatic segmentation and quantification of IPHs are feasible with an accuracy in the range of the inter-observer variability. The method has excellent reproducibility with respect to rescanning and manual initialization.

Joint intensity-and-point based registration of free-hand B-mode ultrasound and MRI of the carotid artery.

PURPOSE: To introduce a semiautomatic algorithm to perform the registration of free-hand B-Mode ultrasound (US) and magnetic resonance imaging (MRI) of the carotid artery. METHODS: The authors' approach combines geometrical features and intensity information. The only user interaction consists of placing three seed points in US and MRI. First, the lumen centerlines are used as landmarks for point based registration. Subsequently, in a joint optimization the distance between centerlines and the dissimilarity of the image intensities is minimized. Evaluation is performed in left and right carotids from six healthy volunteers and five patients with atherosclerosis. For the validation, the authors measure the Dice similarity coefficient (DSC) and the mean surface distance (MSD) between carotid lumen segmentations in US and MRI after registration. The effect of several design parameters on the registration accuracy is investigated by an exhaustive search on a training set of five volunteers and three patients. The optimum configuration is validated on the remaining images of one volunteer and two patients. RESULTS: On the training set, the authors achieve an average DSC of 0.74 and a MSD of 0.66 mm on volunteer data. For the patient data, the authors obtain a DSC of 0.77 and a MSD of 0.69 mm. In the independent set composed of patient and volunteer data, the DSC is 0.69 and the MSD is 0.87 mm. The experiments with different design parameters show that nonrigid registration outperforms rigid registration, and that the combination of intensity and point information is superior to approaches that use intensity or points only. CONCLUSIONS: The proposed method achieves an accurate registration of US and MRI, and may thus enable multimodal analysis of the carotid plaque.

Blood pressure parameters and carotid intraplaque hemorrhage as measured by magnetic resonance imaging: The Rotterdam Study.

Intraplaque hemorrhage (IPH) is a characteristic of the vulnerable atherosclerotic plaque that has been associated with ischemic stroke. Not much is known about determinants of IPH. We studied whether blood pressure parameters are associated with presence of IPH. Within the framework of a prospective population-based cohort study, The Rotterdam Study, the carotid arteries of 1006 healthy participants ≥45 years and with intima-media thickening (≥2.5 mm) on ultrasound were imaged with a 1.5-T magnetic resonance imaging scanner. IPH was defined as a hyperintense signal on a 3D-T1w-GRE magnetic resonance sequence. Generalized estimation equation analysis, adjusted for age, sex, carotid wall thickness, and cardiovascular risk factors, was used to assess the association between blood pressure parameters and IPH. Magnetic resonance imaging of the carotid arteries revealed presence of IPH in 444 of 1860 plaques (24%). Systolic blood pressure and pulse pressure (PP) were significantly associated with IPH after adjustment for age and sex. In multivariate analysis, PP yielded the strongest association, with an odds ratio per SD increase in PP of 1.22 (95% CI, 1.07-1.40). The odds ratio per SD for systolic blood pressure was 1.13 (0.99-1.28). Only PP remained significant after additional adjustment for other blood pressure components. The combination of smoking and isolated systolic hypertension was associated with 2.5 times increased risk of IPH (1.2-5.2). In conclusion, PP was the strongest determinant of IPH independent of cardiovascular risk factors and other blood pressure components. The association between pulsatile flow and IPH may provide novel insights in the development of the vulnerable plaque.