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Acute coronary syndromes due to atherosclerotic coronary artery disease are a leading cause of morbidity and mortality worldwide. Intra-plaque hemorrhage (IPH), caused by disruption of intra-plaque leaky microvessels, is one of the major contributors of plaque progression, causing a sudden increase in plaque volume and eventually plaque destabilization. IPH and its healing processes are highly complex biological events that involve interactions between multiple types of cells in the plaque, including erythrocyte, macrophages, vascular endothelial cells and vascular smooth muscle cells. Recent investigations have unveiled detailed molecular mechanisms by which IPH leads the development of high-risk “vulnerable” plaque. Current advances in clinical diagnostic imaging modalities, such as magnetic resonance image and intra-coronary optical coherence tomography, increasingly allow us to identify IPH in vivo. To date, retrospective and prospective clinical trials have revealed the significance of IPH as detected by various imaging modalities as a reliable prognostic indicator of high-risk plaque. In this review article, we discuss recent advances in our understanding for the significance of IPH on the development of high-risk plaque from basic to clinical points of view.

Magnetic resonance imaging (MRI) is widely used to detect carotid atherosclerotic plaques. Although it is important to evaluate vulnerable carotid plaques containing lipids and intra-plaque hemorrhages (IPHs) using T1-weighted images, the image contrast changes depending on the imaging settings. Moreover, to distinguish between a thrombus and a hemorrhage, it is useful to evaluate the iron content of the plaque using both T1-weighted and T2*-weighted images. Therefore, a quantitative evaluation of carotid atherosclerotic plaques using T1 and T2* values may be necessary for the accurate evaluation of plaque components. The purpose of this study was to determine whether the multi-echo phase-sensitive inversion recovery (mPSIR) sequence can improve T1 contrast while simultaneously providing accurate T1 and T2* values of an IPH. T1 and T2* values measured using mPSIR were compared to values from conventional methods in phantom and in vivo studies. In the phantom study, the T1 and T2* values estimated using mPSIR were linearly correlated with those of conventional methods. In the in vivo study, mPSIR demonstrated higher T1 contrast between the IPH phantom and sternocleidomastoid muscle than the conventional method. Moreover, the T1 and T2* values of the blood vessel wall and sternocleidomastoid muscle estimated using mPSIR were correlated with values measured by conventional methods and with values reported previously. The mPSIR sequence improved T1 contrast while simultaneously providing accurate T1 and T2* values of the neck region. Although further study is required to evaluate the clinical utility, mPSIR may improve carotid atherosclerotic plaque detection and provide detailed information about plaque components. [ABSTRACT FROM AUTHOR]

Acute coronary syndromes due to atherosclerotic coronary artery disease are a leading cause of morbidity and mortality worldwide. Intra-plaque hemorrhage (IPH), caused by disruption of intra-plaque leaky microvessels, is one of the major contributors of plaque progression, causing a sudden increase in plaque volume and eventually plaque destabilization. IPH and its healing processes are highly complex biological events that involve interactions between multiple types of cells in the plaque, including erythrocyte, macrophages, vascular endothelial cells and vascular smooth muscle cells. Recent investigations have unveiled detailed molecular mechanisms by which IPH leads the development of high-risk "vulnerable" plaque. Current advances in clinical diagnostic imaging modalities, such as magnetic resonance image and intra-coronary optical coherence tomography, increasingly allow us to identify IPH in vivo. To date, retrospective and prospective clinical trials have revealed the significance of IPH as detected by various imaging modalities as a reliable prognostic indicator of high-risk plaque. In this review article, we discuss recent advances in our understanding for the significance of IPH on the development of high-risk plaque from basic to clinical points of view.

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. [ABSTRACT FROM AUTHOR]

Intra-plaque hemorrhage (IPH) and lipid core, characteristics of rupture prone carotid plaques, are often visualized in vivo with MRI using T1 weighted gradient and spin echo, respectively. Increasing magnetic field strength may help to identify IPH and lipid core better. As a proof of concept, automatic segmentation of plaque components was performed with the Mahalanobis distance (MD) measure derived from image contrast from multicontrast MR images including inversion recovery spin echo and T1 weighted gradient echo with fat suppression. After MRI of nine formaldehyde-fixated autopsy specimens, the MDs and Euclidean Distances between plaque component intensities were calculated for each MR weighting. The distances from the carotid bifurcation and the size and shape of calcification spots were used as landmarks for coregistration of MRI and histology. MD between collagen/cell-rich area and IPH was largest with inversion recovery spin echo (4.2/9.3, respectively), between collagen/cell-rich area/foam cells and lipid core with T1 weighted gradient echo with fat suppression (26.9/38.2/4.6, respectively). The accuracy of detection of IPH, cell-rich area, and collagen increased when the MD classifier was used compared with the Euclidean Distance classifier. The enhanced conspicuity of lipid core and IPH in human carotid artery plaque, using ex vivo T1 weighted gradient echo with fat suppression and inversion recovery spin echo MRI and MD classifiers, demands further in vivo evaluation in patients. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Background: CD163 is a scavenger receptor for the uptake of haptoglobin–hemoglobin (Hpt–Hb) complexes. The Hpt–Hb complexes are being formed in the plaque in response to intraplaque hemorrhage, a hallmark of atherosclerotic plaque instability. We therefore investigated whether soluble CD163 (sCD163) was elevated in patients with an acute coronary syndrome. Methods: All subjects presenting with chest pain suggestive of myocardial ischemia referred to either the emergency department or the coronary care unit were included in a prospective follow-up study. Plasma was collected and frozen at −80 °C until assayed. sCD163 was measured using a commercially available Elisa assay. Results: Of 526 included chest pain patients, the final diagnosis was non-cardiac chest pain in 244 (46%) patients, non-STEMI in 67 (13%), and STEMI in 215 (41%). The non-STEMI patients were older, used more medication, had undergone more often coronary interventions, but did not differ with respect to risk factors, except for a higher incidence in dyslipidemia. Unexpectedly, sCD163 did not differentiate between patients with non-STEMI or STEMI and the non-cardiac chest pain patients (2.09±0.76 versus 2.24±0.86). Conclusion: Although ACS is characterized by intraplaque hemorrhage, the amount of intraplaque Hb release seems not to be substantial enough to result in a measurable difference in sCD163. [Copyright &y& Elsevier]

Estrogen has previously been shown to inhibit development of early atherosclerotic lesions in hyperlipidemic mice. However, it is still not known whether estrogen also inhibits progression and destabilization of lesions once established and whether there are other effects of long-term hormone therapy in mice. To address this question, male, 20-week old, apolipoprotein E deficient mice were administered 17-β estradiol or placebo subcutaneously for between 4 and 40 weeks. Estrogen administration did not cause regression of established lesions in the carotid arteries, aortic arch and thoracic aorta but prevented the initiation of new lesions in the abdominal aorta and iliac, femoral and popliteal arteries. Although the established lesions were slightly smaller in the innominate artery of the estrogen treated mice, estrogen did not prevent lesion progression. Estrogen administration also had no effect on the frequency of intra-plaque hemorrhage, atrophy of the fibrous cap, medial erosion, and fibro-fatty nodules, but did reduce the frequency of fatty streaks that form on top of or adjacent to the established lesions in the innominate artery. These data suggest that estrogen inhibits the initiation of the fatty streak but does not alter the progression of established lesions through stages of instability and healing. [Copyright &y& Elsevier]