Lipid-rich Necrotic Core Volume Research Articles

Quantitative evaluation of high intensity signal on MIP images of carotid atherosclerotic plaques from routine TOF-MRA reveals elevated volumes of intraplaque hemorrhage and lipid rich necrotic core.

BackgroundCarotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR.MethodsSeventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR.ResultsFor detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 – 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 – 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm3 vs. 53.4 ± 56.3 mm3, p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm3 vs. 111.3 ± 122.7 mm3, p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001).ConclusionMIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.

MR Imaging of Carotid Plaque Composition During Lipid-Lowering Therapy: A Prospective Assessment of Effect and Time Course

The purpose of this study was to test the lipid depletion hypothesis and to establish the time course of change in carotid plaque morphology and composition during lipid therapy using high-resolution magnetic resonance imaging (MRI).Lipid therapy is thought to improve plaque stability and reduce cardiovascular events by targeting the plaque rupture risk features such as large lipid core, thin fibrous cap, and high level of inflammatory infiltrates. However, the plaque stabilizing process during lipid therapy has not been clearly demonstrated in humans and in vivo.Subjects with coronary or carotid artery disease, apolipoprotein B ≥120 mg/dl, and lipid treatment history <1 year, were randomly assigned to atorvastatin monotherapy or to atorvastatin-based combination therapies with appropriate placebos for 3 years. All subjects underwent high-resolution, multicontrast bilateral carotid MRI scans at baseline and annually for 3 years. All images were analyzed for quantification of wall area and plaque composition blinded to therapy, laboratory results, and clinical course.After 3 years of lipid therapy, the 33 subjects with measurable lipid-rich necrotic core (LRNC) at baseline had a significant reduction in plaque lipid content: LRNC volume decreased from 60.4 ± 59.5 mm(3) to 37.4 ± 69.5 mm(3) (p < 0.001) and %LRNC (LRNC area/wall area in the lipid-rich regions) from 14.2 ± 7.0% to 7.4 ± 8.2% (p < 0.001). The time course showed that %LRNC decreased by 3.2 (p < 0.001) in the first year, by 3.0 (p = 0.005) in the second year, and by 0.91 (p = 0.2) in the third year. Changes in LRNC volume followed the same pattern. Percent wall volume (100 × wall/outer wall, a ratio of volumes) in the lipid-rich regions significantly decreased from 52.3 ± 8.5% to 48.6 ± 9.7% (p = 0.002). Slices containing LRNC had significantly more percent wall volume reduction than those without (-4.7% vs. -1.4%, p = 0.02).Intensive lipid therapy significantly depletes carotid plaque lipid. Statistically significant plaque lipid depletion is observed after 1 year of treatment and continues in the second year, and precedes plaque regression. (Using Magnetic Resonance Imaging to Evaluate Carotid Artery Plaque Composition in People Receiving Cholesterol-Lowering Medications [The CPC Study]; NCT00715273).

Multimodality Imaging of Carotid Artery Plaques

This study's objective was to compare (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET), CT, and MRI of carotid plaque assessment. Fifty patients with symptomatic carotid atherosclerosis underwent (18)F-FDG PET/CT and MRI. Correlations and agreement between imaging findings were assessed by Spearman and Pearson rank correlation tests, t tests, and Bland-Altman plots. Spearman rho between plaque (18)F-FDG standard uptake values and CT/MRI findings varied from -0.088 to 0.385. Maximum standard uptake value was significantly larger in plaques with intraplaque hemorrhage (1.56 vs 1.47; P=0.032). Standard uptake values did not significantly differ between plaques with an intact and thick fibrous cap and plaques with a thin or ruptured fibrous cap on MRI. (1.21 vs 1.23; P=0.323; and 1.45 vs 1.54; P=0.727). Pearson rho between CT and MRI measurements varied from 0.554 to 0.794 (P<0.001). For lipid-rich necrotic core volume, the CT-MRI correlation was stronger in mildly (<or=10%) than in severely (>10%) calcified plaques (Pearson rho 0.730 vs 0.475). Mean difference in measurement +/-95% limits of agreement between CT and MRI for minimum lumen area, volumes of vessel wall, lipid-rich necrotic core, calcifications, and fibrous tissue were 0.4+/-18.1 mm(2) (P=0.744), -41.9 +/-761.7 mm(3) (P=0.450), 78.4+/-305.0 mm(3) (P<0.001), 180.5+/-625.7 mm(3) (P=0.001), and -296.0+/-415.8 mm(3) (P<0.001), respectively. Overall, correlations between (18)F-FDG PET and CT/MRI findings are weak. Correlations between CT and MRI measurements are moderate to strong, but there is considerable variation in absolute differences.

Issue Highlights

HomeCirculationVol. 111, No. 21Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published31 May 2005https://doi.org/10.1161/circ.111.21.2711Circulation. 2005;111:2711RHO-KINASE INHIBITOR IMPROVES INCREASED VASCULAR RESISTANCE AND IMPAIRED VASODILATION OF THE FOREARM IN PATIENTS WITH HEART FAILURE, by Kishi et al.Although increased vascular tone is a well-recognized feature in heart failure, the mechanisms responsible are incompletely understood. When activated by the small GTPase Rho, Rho-kinase inhibits the activity of myosin light chain phosphatase, thereby increasing vascular smooth muscle contraction. A Rho-kinase inhibitor, fasudil, was administered via the brachial artery to 26 patients with NYHA functional class II and III heart failure and to 26 control subjects, and forearm vascular resistance was determined by using plethesmography. Fasudil caused vasodilation and improved the vasodilation induced by reactive hyperemia in the patients with heart failure but not in the control subjects. By comparison, nitroprusside caused vasodilation in both groups. These observations suggest the involvement of Rho-kinase in mediating increased vascular tone in heart failure and raise the possibility of a new therapeutic approach. See p 2741.PRESENCE OF INTRAPLAQUE HEMORRHAGE STIMULATES PROGRESSION OF CAROTID ATHEROSCLEROTIC PLAQUES: A HIGH-RESOLUTION MAGNETIC RESONANCE IMAGING STUDY, by Takaya et al.Hemorrhage into atherosclerotic plaques has been recently reported in histopathologic studies, associated with larger plaque necrotic cores, as well as greater lipid content and macrophage infiltration. Whether intraplaque hemorrhage is simply associated with larger or more complex plaques or indeed stimulates plaque progression has not been clarified. In this issue, Takaya and colleagues use serial cardiovascular magnetic resonance imaging studies of the carotid arteries over 18 months in patients with carotid atherosclerosis to demonstrate that the presence of intraplaque hemorrhage on the initial examination was associated with greater progression of plaque atherosclerosis. Those with hemorrhage at baseline had greater progression of lipid-rich necrotic core volume as well as wall volume, independent of the volume of hemorrhage components, and were also more likely to have recurrent plaque hemorrhage. These important data suggest that intraplaque hemorrhage contributes significantly to the acceleration of atherosclerosis in this vascular bed. See p 2768.EXPRESSION OF HUMAN MYELOPEROXIDASE BY MACROPHAGES PROMOTES ATHEROSCLEROSIS IN MICE, by McMillen et al.The relation between oxidative stress and atherosclerosis is complex. Recent developments suggest that myeloperoxidase, a neutrophil enzyme, may mediate oxidative events important to atherosclerosis. Early studies examining how this enzyme may promote atherosclerosis were hampered by the lack of an appropriate animal model. This hurdle to studying myeloperoxidase has now been overcome by the development of a mouse expressing the human myeloperoxidase gene. McMillen and colleagues report this new finding and demonstrate how bone marrow-derived human myeloperoxidase can accelerate atherosclerosis. See p 2798.Visit http://www.circ.ahajournals.org:Cardiology Patient PageTreatment of Elevated Cholesterol. See p e360.Images in Cardiovascular MedicineA Case of Transient Constrictive Pericarditis. See p e364.Constrictive Epicarditis as an Unusual Cause of Constrictive Physiology: Typical Presentation With Unusual Pathology. See p e365. Download figureDownload PowerPointTwo-Dimensional and Real-Time Three-Dimensional Echocardiographic Fetal Diagnosis of Aorto-Ventricular Tunnel. See p e367.CorrespondenceSee p e369. Previous Back to top Next FiguresReferencesRelatedDetails May 31, 2005Vol 111, Issue 21 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.111.21.2711 Originally publishedMay 31, 2005 PDF download Advertisement

Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques

Previous studies suggest that erythrocyte membranes from intraplaque hemorrhage into the necrotic core are a source of free cholesterol and may become a driving force in the progression of atherosclerosis. We have shown that MRI can accurately identify carotid intraplaque hemorrhage and precisely measure plaque volume. We tested the hypothesis that hemorrhage into carotid atheroma stimulates plaque progression. Twenty-nine subjects (14 cases with intraplaque hemorrhage and 15 controls with comparably sized plaques without intraplaque hemorrhage at baseline) underwent serial carotid MRI examination with a multicontrast weighted protocol (T1, T2, proton density, and 3D time of flight) over a period of 18 months. The volumes of wall, lumen, lipid-rich necrotic core, calcification, and intraplaque hemorrhage were measured with a custom-designed image analysis tool. The percent change in wall volume (6.8% versus -0.15%; P=0.009) and lipid-rich necrotic core volume (28.4% versus -5.2%; P=0.001) was significantly higher in the hemorrhage group than in controls over the course of the study. Furthermore, those with intraplaque hemorrhage at baseline were much more likely to have new plaque hemorrhages at 18 months compared with controls (43% versus 0%; P=0.006). Hemorrhage into the carotid atherosclerotic plaque accelerated plaque progression in an 18-month period. Repeated bleeding into the plaque may produce a stimulus for the progression of atherosclerosis by increasing lipid core and plaque volume and creating new destabilizing factors.