Degree of carotid plaque calcification in relation to symptomatic outcome and plaque inflammation

OBJECTIVE: We undertook this study to quantitate differences in the degree of calcification between symptomatic and asymptomatic plaques removed at carotid endarterectomy (CEA) and to determine associated extent of plaque macrophage infiltration, a histopathologic feature of plaque instability. METHODS: CEA plaques (n = 48) were imaged at 1.25-mm intervals with spiral computed tomography (CT; 10-15 images per plaque). Indications for CEA were transient ischemic attack (n = 16), stroke (n = 5), amaurosis (n = 4), and critical asymptomatic stenosis (n = 23). The percent area calcification for each plaque was determined in spiral CT serial sections and averaged for each plaque. In 31 of 48 plaques macrophage infiltration was quantitated in corresponding histologic sections with immunohistochemical techniques. RESULTS: The mean (+/- SD) age of patients with symptomatic and asymptomatic plaques was 66 +/- 7 years vs 71 +/- 7 years, respectively, and degree of stenosis was 76% versus 82%, respectively (P =.05). Atherosclerosis risk factors were similar between groups. Percent plaque area calcification was twofold greater in asymptomatic versus symptomatic plaques (48% +/- 19% vs 24% +/- 20%, respectively; P <.05). At receiver operating characteristic curve analysis, 80% of symptomatic plaques were below and 87% of asymptomatic plaques were above a cutoff point of 30% plaque area calcification. Macrophage burden was greater in the symptomatic plaques than in the asymptomatic plaques (52% vs 23%; P <.03). A strong inverse relationship between the degree of plaque calcification and macrophage infiltration was found in critical carotid stenoses (r = -0.87; P <.001). CONCLUSIONS: Symptomatic plaques are less calcified and more inflamed than asymptomatic plaques. Regardless of clinical outcome, a strong inverse correlation was found between the extent of carotid plaque calcification and the intensity of plaque fibrous cap inflammation as determined by the degree of macrophage infiltration. Carotid plaque calcification is associated with plaque stability, and is a potential spiral CT in vivo quantitative marker for cerebrovascular ischemic event risk.     

Comparison of Vascular Smooth Muscle Cell Apoptosis and Fibrous Cap Morphology in Symptomatic and Asymptomatic Carotid Artery Disease

The biological cascades that lead to carotid plaque disruptions and symptoms are largely unknown. Certain cellular events within the plaque might be responsible for destabilizing the plaque, though the popular belief is that the plaque size is directly related to symptoms. The aim of our study was to assess the morphology of the fibrous cap and apoptosis in the plaque and compare these two pathological features in symptomatic and asymptomatic carotid artery disease. Our work was carried out in plaques obtained following carotid endarterectomy performed for symptomatic disease (including hemispheric transient ischemic attacks, amaurosis fugax, or stroke) or asymptomatic high-grade severe stenosis. Scion images of Gomori's stained sections were used to measure fibrous cap thickness and area. TUNEL assay was performed to assess the extent of apoptosis. The results indicated that the area of the fibrous cap did not significantly correlate with the presence of symptoms. There was a higher percentage of apoptotic nuclei and the thinner fibrous cap in symptomatic plaques than in asymptomatic plaques. This finding suggests that these factors might be involved in destabilizing plaque, causing rupture and leading to symptomatic carotid disease.     

Structural analysis and magnetic resonance imaging predict plaque vulnerability: a study comparing symptomatic and asymptomatic individuals

BACKGROUND: More than half of all cerebral ischemic events are the result of rupture of extracranial plaques. The clinical determination of carotid plaque vulnerability is currently based solely on luminal stenosis; however, it has been increasingly suggested that plaque morphology and biomechanical stress should also be considered. We used finite element analysis based on in vivo magnetic resonance imaging (MRI) to simulate the stress distributions within plaques of asymptomatic and symptomatic individuals. METHODS: Thirty non-consecutive subjects (15 symptomatic and 15 asymptomatic) underwent high-resolution multisequence in vivo MRI of the carotid bifurcation. Stress analysis was performed based on the geometry derived from in vivo MRI of the carotid artery at the point of maximal stenosis. The finite element analysis model considered plaque components to be hyperelastic. The peak stresses within the plaques of symptomatic and asymptomatic individuals were compared. RESULTS: High stress concentrations were found at the shoulder regions of symptomatic plaques, and the maximal stresses predicted in this group were significantly higher than those in the asymptomatic group (508.2 +/- 193.1 vs 269.6 +/- 107.9 kPa; P = .004). CONCLUSIONS: Maximal predicted plaque stresses in symptomatic patients were higher than those predicted in asymptomatic patients by finite element analysis, suggesting the possibility that plaques with higher stresses may be more prone to be symptomatic and rupture. If further validated by large-scale longitudinal studies, biomechanical stress analysis based on high resolution in vivo MRI could potentially act as a useful tool for risk assessment of carotid atheroma. It may help in the identification of patients with asymptomatic carotid atheroma at greatest risk of developing symptoms or mild-to-moderate symptomatic stenoses, which currently fall outside current clinical guidelines for intervention.     

Fibrous cap thickness and smooth muscle cell apoptosis in high-grade carotid artery stenosis.

OBJECTIVE: There is growing evidence that, in high-grade internal carotid artery (ICA) stenosis, continuous fibrous cap thinning is not mandatory for plaque rupture and symptom development. The possibility that smooth muscle cell (SMC) apoptosis is involved in loss of fibrous cap volume has only been examined in a limited number of patients with high grade carotid artery stenosis. METHODS: Endarterectomy specimens from n = 38 consecutive patients undergoing surgery for high-grade ICA stenosis (> or = 70%) were transversely sectioned at 2 mm intervals. Plaque instability was defined clinically, by a history of recent ischemic symptoms (< 60 days before surgery; n = 19) attributable to the stenosis, or histopathologically by the presence of plaque rupture (n = 14). Detailed morphometric analyses of the fibrous cap was based on routine stains; for DNA in situ end labeling the TUNEL technique was used. SMCs were identified by immunostaining for SMC actin. RESULTS: We found no significant difference between symptomatic/asymptomatic or ruptured/unruptured plaque with respect to various morphometric measures of the fibrous cap (i.e. mean area, number of plaque sections with fibrous cap, necrotic core-to-lumen distance at its thinnest or thickest part). The mean (+/- SD) apoptotic SMCs per thousand within the fibrous cap was significantly higher in symptomatic vs. asymptomatic (64.53 +/- 77.3 vs. 6.71 +/- 11.9; P<0.001) but not in ruptured plaques (43.3 +/- 64.4 vs. 30.1 +/- 60.9; P=0.117). CONCLUSIONS: These data suggest that continuous thinning of the fibrous cap is not an essential prerequisite for plaque rupture in ICA stenosis. Symptomatic, but not ruptured plaque, were associated with the highest number of apoptotic SMC. Thus, it seems unlikely that SMC apoptosis promotes plaque rupture by fibrous cap thinning.     

Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques

BACKGROUND: Instability and rupture of carotid atherosclerotic plaques leads to thromboemboli and ischemic symptoms. Angiogenesis occurs within atherosclerotic plaques, and plaque vulnerability and symptomatic carotid disease have been associated with increased numbers of microvessels. In addition to microvessel number, it is possible that the phenotypes of intraplaque vessels could influence plaque stability. To test this, the morphology and maturity of vessels within plaques from symptomatic and asymptomatic patients was determined. METHODS: Carotid plaques were collected after endarterectomy from a cohort of 13 asymptomatic patients and 30 symptomatic patients. Plaques were sectioned and immunostained for the presence of endothelial cells, vascular smooth muscle cells, macrophages, and vascular endothelial growth factor. Sections were assessed for microvessel morphology, maturity as judged by smooth muscle cell cover, and the presence of vascular endothelial growth factor and macrophages. RESULTS: Two types of vascular structure were observed within plaques, microvessels and dilated, highly irregular multilobular vessels. These irregular dysmorphic vessels were found almost exclusively in plaques from symptomatic patients. The dysmorphic vessels lacked smooth muscle cells and were highly immature. Plaques also contained vascular endothelial growth factor, and this was observed adjacent to the dysmorphic vessels. This growth factor was found colocalized with macrophages. CONCLUSIONS: Symptomatic carotid plaques contain abnormal, immature microvessels similar to those found in tumors and healing wounds. Such vessels could contribute to plaque instability by acting as sites of vascular leakage by inflammatory cell recruitment. The immature vessels within plaques may be therapeutic targets for promoting plaque stabilization.     

Changes in carotid plaque echomorphology with time since a neurologic event

PURPOSE: Symptomatic carotid plaques are characterized by reduced fibrous tissue content, increased lipid content, intraplaque hemorrhage, and cap rupture. This confers an increased stroke risk. Plaque remodelling reduces this risk, however, and this study has evaluated differences in echomorphology at varying times after a neurologic event. METHODS: Gray scale medians (GSM +/- interquartile ranges) were measured using the best single longitudinal (SLV) and multiple cross-sectional views (MCSV; transverse views, 5-mm intervals throughout plaque) on B-mode ultrasound images of 61 carotid plaques (70% to 99%) causing symptoms < or =30 (n = 20), 31 to 90 (n = 10), 91 to 180 (n = 16), or >180 days (n = 15). The results were compared with those in 47 asymptomatic plaques. Plaque echolucency (SLV-GSM, MCSV(min)-GSM [cross-sectional image with lowest GSM]) and heterogeneity (MCSV(max-min)-GSM [highest minus lowest GSM of cross-sectional views]) were determined. RESULTS: In symptomatic plaques, echolucency was maximal < or =30 days of the presenting neurologic event (SLV-GSM, P = .009; MCSV(min)-GSM, P = .004). Although this diminished between 31 to 90 days, MCSV measurements in particular suggested increased echolucency (P = .042 at >180 days) and continuing heterogeneity (P = .01 at 91 to 180 days) beyond that time. CONCLUSIONS: Plaque echolucency was maximal < or =30 days of a neurologic event but diminished after 1 to 3 months, suggesting remodelling of unstable plaques. Continued features of increased echolucency and heterogeneity >91 days, however, suggests an increased stroke risk in these patients compared with that of the general population.     

Histologic characteristics of carotid artery plaque

Carotid plaque characteristics associated with the production of symptoms were identified with quantification of carotid plaque constituents in high-grade stenotic asymptomatic (n = 8) and symptomatic (n = 44) plaques. Asymptomatic plaques contained significantly more fibrous/collagen material (88%) than symptomatic plaques (66%) (p less than 0.05). Hemorrhage constituted 2% and 1% of asymptomatic and symptomatic plaques, respectively. The predominant nonfibrous material was a pink amorphous material mixed with cholesterol, which composed 7% of asymptomatic and 27% of symptomatic plaques (p less than 0.05). No relationship was found between plaque composition and the number of ipsilateral ischemic neurologic events, nor was there evidence of a healing process. B-mode ultrasound scanning had a sensitivity of 94% in identifying plaque with greater than 80% fibrous content. We believe that plaque composition may be a useful discriminating factor in selecting asymptomatic patients for carotid endarterectomy.     

Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging-based finite element analysis

OBJECT: Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses. METHODS: Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted. RESULTS: There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition. CONCLUSION: Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging-based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.     

Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques

BACKGROUND: The correlation of B-mode ultrasonographic morphology with histologic characteristics of atherosclerotic carotid plaques remains ill-defined. The classification of plaques with recently reported measures of plaque echogenicity and heterogeneity has been unsatisfactory. We used computer-assisted duplex ultrasound (DU) scan image analysis to determine echogenicity of specific tissues in control subjects. This information was used to quantify each tissue in imaged carotid plaques with pixel distribution analysis (PDA). These objective observations then were quantitatively compared with plaque histology in symptomatic and asymptomatic patients. METHODS: We performed standardized DU scanning of healthy tissues in 10 volunteer subjects and of 20 carotid artery plaques (7 symptomatic and 13 asymptomatic) in 19 patients with carotid stenosis. The plaques underwent histologic analysis after carotid endarterectomy. The grayscale intensity ranges of blood, lipid, fibromuscular tissue, and calcium were calculated in the control subjects. With computer-assisted image analysis, B-mode images of plaques were linearly scaled to normalize data. Pixel distribution within the images then was analyzed. The grayscale ranges of known tissues obtained from control subjects helped define the amount of intraplaque hemorrhage, lipid, fibromuscular tissue, and calcium within carotid plaque images. This analysis was correlated with tissue composition measurements on histologic sections of excised plaques. RESULTS: The median grayscale intensity (range) in control subjects was 2 (0 to 4) for blood, 12 (8 to 26) for lipid, 53 (41 to 76) for muscle, 172 (112 to 196) for fibrous tissue, and 221 (211 to 255) for calcium. PDA-derived predictions for blood, lipid, fibromuscular tissue, and calcium within carotid plaques correlated significantly with the histologic estimates of each tissue respectively (blood: P =.012; lipid: P =.0006; fibromuscular: P =.035; and calcium: P =.0001). A significantly higher amount of blood and lipid was seen within symptomatic plaques compared with asymptomatic ones (P =.0048 and P =.026, respectively). Conversely, a larger amount of calcification was noted within asymptomatic plaques (P =.0002). CONCLUSION: Computer-assisted PDA of DU scan images accurately quantified intraplaque hemorrhage, fibromuscular tissue, calcium, and lipid. Symptomatic plaques had lower calcium content but larger amounts of intraplaque hemorrhage and lipid. Quantitative PDA may be used to determine carotid plaque tissue composition to assist in the identification of symptomatic and potentially unstable asymptomatic plaques.     

The relationship between carotid plaque composition and neurologic symptoms

Variations in plaque composition, particularly an increased lipid concentration, could make carotid plaques unstable and prone to embolization. To investigate this hypothesis, 35 carotid bifurcation plaques from 31 patients undergoing carotid endarterectomy (20 symptomatic, 11 asymptomatic) were prospectively analyzed. Plaque total lipid, cholesterol, collagen, and Ca2+ content were determined, and the plaque collagen was fractionated into pepsin-soluble collagen (PSC) (indicative of less crosslinked, more recently synthesized collagen) and pepsin-insoluble collagen. Preoperative serum lipid and plasma lipoprotein levels were also obtained in all patients. Results revealed that plaques removed from symptomatic patients contained significantly more total lipid and cholesterol (P less than 0.001) than those removed from asymptomatic patients. There was also an increased amount of pepsin-soluble collagen in symptomatic plaques, potentially indicating increased metabolic activity (P less than 0.05). In addition, mean plasma low-density lipoprotein cholesterol was higher in symptomatic patients than in asymptomatic patients (P less than 0.05). Since lipid-laden plaques can potentially be identified by B-mode ultrasound, it may be important to remove these plaques in asymptomatic patients or, alternatively, to attempt to lower the plaque cholesterol by lipid-lowering maneuvers.     

Contribution of angiotensin-converting enzyme and angiotensin II to ischemic stroke: their role in the formation of stable and unstable carotid atherosclerotic plaques

BACKGROUND: The angiotensin-converting enzyme/angiotensin II (ACE/Ang II) system is a strong contributor to intimal hyperplasia in atherosclerotic lesions. To illuminate its role in ischemic stroke, we examined the expression of ACE/Ang II in stable and unstable carotid atherosclerotic plaques from symptomatic and asymptomatic patients. METHODS: Using immunohistochemical methods, we studied differences between carotid atherosclerotic lesions obtained at carotid endarterectomy (CEA) from symptomatic (n = 36) and asymptomatic (n = 28) patients. The specimens were classified as stable (n = 30) and unstable (n = 34) plaques, and their fibrous cap, lipid core, and shoulder lesion were examined. We used antibodies against smooth muscle cells (SMC), macrophages, endothelial cells (EC), ACE, and Ang II. RESULTS: Of 28 lesions from asymptomatic patients, 20 (71.4%) manifested features characteristic of stable plaques: the expression of ACE/Ang II co-localized with SMC, EC, and macrophages in the shoulder lesion. In contrast, 26 of 36 symptomatic lesions (72.2%) exhibited the typical features of unstable plaques: dense accumulations of macrophages near the luminal surface in the shoulder lesion and weak immunoreactivity for ACE/Ang II, EC, and SMC. Furthermore, most of the lesions were accompanied by early stage atherosclerotic lesions (satellite lesions) that were strongly immunoreactive with macrophages, EC, and ACE/Ang II. CONCLUSIONS: ACE/Ang II expression may induce the proliferation of SMC and EC and result in the formation of carotid atherosclerotic plaques with a thick fibrous cap. Notably, the shoulder lesion of unstable plaques exhibited a thin fibrous cap and faintly expressed ACE/Ang II. Lack of the ACE/Ang II system may contribute to the final step in plaque rupture.     

Differences in the detection of cyclo-oxygenase 1 and 2 proteins in symptomatic and asymptomatic carotid plaques.

BACKGROUND: The expression of cyclo-oxygenase (COX) 1 and 2 has been demonstrated in atherosclerotic arteries. In the present study this was correlated with symptoms arising from a carotid plaque. METHODS: Carotid plaques from 12 asymptomatic patients were compared with 11 plaques from patients who had had neurological symptoms within the preceding 30 days. Sections were stained with haematoxylin and eosin, elastin van Gieson and goat antihuman antibodies to COX-1 and COX-2. Plaque morphology was correlated with neurological symptoms. The area with positive COX-1 and COX-2 staining was measured by computerized planimetry in entire cross-sections and in specific areas of the plaque. RESULTS: There was a significant association between cap thinning and plaque rupture with symptoms (P = 0.003). The percentage area of positive staining in entire cross-sections for both COX-1 and COX-2 was significantly greater in symptomatic plaques (P = 0.001 and 0.0004 respectively). Staining in symptomatic plaques was significantly greater in the cap (COX-1: P = 0.001; COX-2: P = 0.0001) and shoulder (COX-1: P = 0.008; COX-2: P = 0.007) regions of the plaque. COX-1 expression in the sclerotic area was not increased (P = 0.15) although COX-2 staining was significantly greater (P = 0.04). CONCLUSION: Both COX-1 and COX-2 detection was increased in symptomatic plaques. COX may contribute to plaque rupture and the onset of symptoms.     

Selected haemostatic factors in carotid bifurcation plaques of patients undergoing carotid endarterectomy.

OBJECTIVE: To determine the concentration of selected haemostatic factors (HFs): thrombin-antithrombin complexes (TAT), antithrombin (AT), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1) and D-dimers in carotid bifurcation plaques and to compare plaque composition in different subgroups of patients (mainly those with symptomatic and asymptomatic carotid stenosis). MATERIALS AND METHODS: Thirty-eight consecutive patients (20 symptomatic, 18 asymptomatic) undergoing carotid endarterectomy were enrolled in the study. The concentration of selected HFs in carotid plaques was measured using mainly enzyme immunoassay (ELISA). Simultaneously, the concentration of HFs in plasma was also obtained. RESULTS: Symptomatic plaques contained significantly more TAT complexes (p=0.03). AT was found only in nine out of 38 carotid plaques and was present mainly in symptomatic carotid plaques (n=8/9)(p<0.006). No significant differences were found between symptomatic and asymptomatic carotid plaques with respect to t-PA, PAI-1 and D-dimers concentration. There was an increased concentration of TAT (p<0.001), t-PA (p<0.02) and D-dimers (p<0.02) in carotid plaques of diabetic patients. Patients with coexisting intermittent claudication had elevated levels of D-dimers in carotid plaques (p<0.02). The only positive correlation was demonstrated between the concentration of AT in plasma and carotid plaques (R=0.76; p=0.02). CONCLUSIONS: All the evaluated HFs are the components of a carotid plaque. Symptomatic patients have increased concentration of TAT complexes in a carotid plaque. The symptomatic carotid plaque contains AT more frequently, which correlates positively with AT plasma levels. The most marked changes in the carotid plaque haemostatic composition (expressed by elevated levels of TAT, t-PA and D-dimers) have diabetic patients.     

Macrophage accumulation within the cap of carotid atherosclerotic plaques is associated with the onset of cerebral ischemic events.

PURPOSE: Macrophage accumulation is associated with aortic and coronary plaque instability. The macrophage content of carotid plaques removed at carotid endarterectomy (CE) was assessed, and the relevance to the onset of ipsilateral cerebral ischemic events (CIE) was examined. METHODS: Carotid plaques from patients undergoing CE were examined (group I, symptomatic stenoses, n = 28; group II, high-grade asymptomatic stenosis, n = 7). The plaques were stained with monoclonal antimacrophage antibody (HAM56), and the interval since the last CIE was recorded. The percentage area of the cap, shoulder, and entire sclerotic region was quantified by computerized planimetry. RESULTS: The macrophage content of the cap, shoulder, and sclerotic region in all 35 plaques was 1.14% (interquartile range, 0.56 to 3.86), 1.03% (0.51 to 2.15), and 0.49% (0.27 to 0.63), respectively (cap vs sclerotic, P <.01; shoulder vs sclerotic, P <. 01; cap vs shoulder, P =.23). In 18 plaques that were removed less than 180 days after the last CIE, the macrophage content of the cap, shoulder, and entire sclerotic region was 2.41% (0.95 to 4.81), 0. 83% (0.40 to 2.52), and 0.53% (0.38 to 0.71), respectively (cap vs sclerotic, P =.01; cap vs shoulder, P =.01). The content in the cap of these plaques was greater than in plaques removed more than 180 days after symptoms, or asymptomatic plaques (n = 17; 0.62% [0.44 to 1.25], P =.01). The cap macrophage content was inversely related to the time since the last CIE (r = -0.414, P =.029). CONCLUSION: In patients requiring CE, macrophage accumulation was maximal within the cap of carotid plaques and greatest in plaques removed less than 180 days after the last CIE. These findings and the inverse relationship between macrophage content and the interval since symptoms support the hypothesis that macrophage accumulation is associated with plaque instability.     

Angiogenesis in atherosclerotic plaque obtained from carotid endarterectomy: association between symptomatology and plaque morphology

Carotid plaque with hemorrhage leads to cerebral embolism and ischemic stroke. Plaque angiogenesis and angiogenetic factors such as vascular endothelial growth factor (VEGF) are critical in the progression of atherosclerotic carotid plaque and intraplaque hemorrhage. The correlation between plaque angiogenesis and presence of clinical symptoms was studied in 41 specimens obtained during carotid endarterectomy from 20 symptomatic and 21 asymptomatic patients treated for carotid artery stenosis. Histological findings using hematoxylin-eosin and immunohistochemical staining against von Willebrand factor and VEGF were examined. Intraplaque hemorrhage, calcification, necrosis, and invasion of foam cells were frequently observed in the carotid plaques from symptomatic patients compared with asymptomatic patients. Higher microvessel density was found in the carotid plaques with necrosis and invasion of foam cells compared with plaques without necrosis and/or foam cell invasion, and higher expression of VEGF was found from symptomatic patients compared with asymptomatic patents. These results suggest that plaque angiogenesis and higher level of VEGF expression may enhance the progression of ischemic symptoms in patients with carotid artery stenosis. Invasive macrophages in the plaque of symptomatic patients increase levels of VEGF and might enhance plaque angiogenesis and atherosclerosis progression.     

颈动脉粥样斑块的MRI诊断价值

目的：探讨颈动脉粥样斑块的MRI影像特点,以提高对颈动脉粥样斑块成分及性质的认识。方法回顾性分析2013年11月～2014年5月期间13例颈动脉粥样斑块的MRI病例资料,并与颈动脉内膜剥脱术的病理结果相对照,总结其影像信号特点。结果13个病例共18个粥样硬化斑块,颈动脉内膜剥脱术取出13个斑块;13例斑块存在脂质坏死池;6例纤维帽撕裂;7例斑块内出血;11例斑块内钙化;4例炎性细胞浸润。结论颈动脉粥样斑块的磁共振信号具有特征性,磁共振成像能有效评估斑块的稳定性。     

Vulnerable carotid arterial plaque causing repeated ischemic stroke can be detected with B-mode ultrasonography as a mobile component: Jellyfish sign

Mobile plaque is associated with increased risk of ischemic stroke, but definitions have remained unclear. We have previously reported that carotid ultrasonography can detect the mobile component of the carotid plaque surface, which rises and falls in a manner inconsistent with arterial pulsatile wall motion (Jellyfish sign). However, clinical and pathological features of Jellyfish sign remain unclear. The subjects comprised of 165 patients with carotid plaque and degree of area stenosis ≥50% on ultrasonography. Using magnetic resonance imaging, we quantified intraplaque hemorrhage (IPH) and defined ischemic stroke in each patient. Fifteen surgical specimens were obtained by carotid endarterectomy, and pathological features (area of fibrous cap and intraplaque atheromatous lesion) were compared with ultrasonographic plaque surface movement rate. Carotid plaques with IPH were seen in 78 cases, with Jellyfish sign in 31 cases. Jellyfish sign was not detected in patients without IPH. In these 15 patients, the fibrous cap covered the atheromatous lesion, and cap thickness correlated negatively with Jellyfish-positive plaque surface movement rate. Kaplan–Meier and Cox multiple regression analysis demonstrated that the most important predictor of ischemic stroke during follow-up is Jellyfish sign, not IPH. Stroke events in patients with Jellyfish sign repeated within a short interval after diagnosis. Jellyfish sign on ultrasonography is a sign of high-risk plaque vulnerability, suggesting rupture of the fibrous cap associated with the release of thrombogenic factors into the arterial lumen, and resulting in repeated ischemic stroke during a short interval after diagnosis.     

Computer-assisted carotid plaque analysis: characteristics of plaques associated with cerebrovascular symptoms and cerebral infarction.

OBJECTIVE: to correlate the echostructural characteristics of carotid plaques with neurological symptoms and cerebral infarcts. MATERIALS: one hundred and five plaques were studied in 74 patients by colour-flow duplex ultrasound: 39 were symptomatic and 37 were associated with brain infarction on CT scanning. METHODS: the images were digitalised for computer-assisted image standardisation and divided in homogenous (n=67) and heterogenous (n=38) groups. Parameters of the plaque image were analysed. RESULTS: global echogenicity was significantly lower in symptomatic and in CT(+)plaques (p<0.05). For homogenous plaques, an echogenic cap (EC) was visualised in 8.3% of symptomatic vs. 33.9% of asymptomatic (p<0. 05) and in 7.7% for plaques that were CT(+)vs. 37.7% for CT(-)(p<0. 05). Surface disruption was visualised in 50% of symptomatic vs. 8. 5% of asymptomatic (p=0.002) and in 46% of CT(+)vs. 9.4% of CT(-)plaques (p=0.002). For heterogenous plaques, the echolucent region was juxtaluminal in 67% of symptomatic and CT(+)plaques vs. 33% in asymptomatic and CT(-)(p<0.01). CONCLUSION: echolucent plaques are associated with a higher neurological risk. In homogenous plaques the absence of an echogenic cap and disruption of the plaque surface also correlates with symptoms. In heterogenous plaques, juxtaluminal location of the echolucent region is an additional marker of increased risk.     

Imaging of the high-risk carotid plaque: magnetic resonance imaging

The emergence of the concept of high-risk atherosclerotic plaque has led to considerable interest in noninvasive imaging techniques to identify high-risk features before clinical sequelae. For plaques in the carotid arteries, magnetic resonance imaging has undergone considerable histologic validation to link imaging features to indicators of plaque instability, including plaque burden, intraplaque hemorrhage, fibrous cap disruption, lipid rich necrotic core, and calcification. Recently introduced imaging technologies, especially those focused on three-dimensional imaging sequences, are now poised for integration into the clinical workup of patients with suspected carotid atherosclerosis. The purpose of this article is to review the carotid plaque magnetic resonance imaging techniques that are most ready for integration into the clinic.     

Immunophenotypic Characterisation of Carotid Plaque: Increased Amount of Inflammatory Cells as an Independent Predictor for Ischaemic Symptoms

OBJECTIVES: To investigate the inflammatory response within intact carotid plaques from carotid eversion endarterectomy (CEE) to determine the relationship between immunohistological plaque morphology and ischaemic cerebrovascular symptoms. MATERIAL AND METHODS: Intact CEE plaques from 71 patients with high-grade (>70%) stenosis undergoing CEE (group I, symptomatic, n=42; group II, asymptomatic, n =29) and 12 normal postmortem arteries (control group) were analysed with specific antibodies to inflammatory cells (T-Lymphocytes (CD3, CD4), cytotoxic T-cells (CD8), B-lymphocytes (CD20), natural killer cells (CD57), macrophages (CD68)), endothelial adhesion molecules (ICAM-1 (CD54), P-selectin (CD62P), E-selectin (CD62E), VCAM-1 (CD106) and T-lymphocyte co-stimulatory molecule (CD40)) and procoagulatory modulators (thrombomodulin (CD141), tissue factor (CD142)). Both groups were matched for gender, age, risk factors, degree of carotid artery stenosis. Plaques were measured using a semiquantitative score system in a blinded fashion by two observers. Statistical analysis of the group differences were performed by using the Kruskal-Wallis test and the Multitest Procedure with Permutation-Testing. Significance was taken as a p<0.05. RESULTS: There were significantly more inflammatory cells, an overexpression of P-selectin and the procoagulatory markers thrombomodulin and tissue factor in symptomatic compared to both asymptomatic plaques and the ones of the control group. In both groups there was no significance for ICAM-1, VCAM-1, macrophages and co-stimulatory molecule CD40. There was also no significance for any factor between the asymptomatic and the control group. However, the differences between the symptomatic and the asymptomatic group were highly significant for all factors. CONCLUSION: These data suggest that structural changes and inflammatory damage within the individual plaque seems to be a critical step in promoting plaque rupture with embolic sequelae.