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.     

Carotid artery atheroma: comparison of preoperative B-mode ultrasound appearance with carotid endarterectomy specimen pathology

This paper describes a prospective study comparing the preoperative Duplex ultrasound appearance of carotid bifurcation atheroma with the pathological characteristics found in the endarterectomy specimens of the same vessels. Initial studies of carotid atheroma using Duplex scanning classified plaques into heterogeneous and homogeneous and found a strong correlation between heterogeneous lesions and the presence of intraplaque haemorrhage or ulceration in the endarterectomy specimen. The B-mode classification of plaque appearance described in this paper is an expansion of the above classification. The study group comprised 220 patients who underwent 244 procedures. The indication for carotid endarterectomy was symptomatic disease in the great majority of cases. We found a high incidence of unstable plaque pathology in the operative specimens, and a predominance of the more echolucent ultrasound plaque appearances (types 1 and 2). There is a statistically significant relationship (p less than 0.001) between ultrasound appearance types 1 and 2 and the presence of either intraplaque haemorrhage or ulceration in the endarterectomy specimen.     

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.     

Critical carotid stenoses: morphologic and chemical similarity between symptomatic and asymptomatic plaques

To identify microanatomic and chemical features that may mark the transition from asymptomatic to symptomatic atherosclerotic carotid lesions, we evaluated 62 carotid artery bifurcation plaques including 45 high-grade stenoses removed at endarterectomy and 17 nonstenotic plaques recovered at autopsy. Morphologic features were evaluated on multiple-interval histologic sections and were graded for the presence of hemorrhage, ulceration, thrombosis, lumen surface irregularity, and calcification. Plaque hemorrhage, recent and remote, was found in most of the specimens, and did not discriminate between symptomatic and asymptomatic stenotic plaques. High-grade carotid stenotic plaques were associated with a significantly higher incidence of ulceration (53%), thrombosis (49%), and lumen irregularity (78%) when compared to nonstenotic asymptomatic plaques (6%, 0%, and 17%, respectively; p less than 0.01). Although these features were more prominent in lesions that produced symptoms, they were present in 80% of the stenotic bifurcations, and did not distinguish between symptomatic and asymptomatic endarterectomy plaques. No significant differences were found between symptomatic and asymptomatic high-grade lesions with respect to collagen, DNA, total cholesterol, fibrinogen, lipase, elastase, or collagenase content. We conclude that intraplaque hemorrhage is commonly seen in carotid plaques even without severe stenosis, and it does not appear to be a dominant determinant of symptoms. Ulceration and surface thrombi that may lead to cerebral embolization are prominent features in markedly stenotic plaques even when symptoms are absent. The disruptive processes that underlie plaque instability appear to be closely associated with plaque size and stenosis rather than plaque composition.     

Angiogenesis and the atherosclerotic carotid plaque: an association between symptomatology and plaque morphology.

PURPOSE: Symptomatic carotid disease resulting from generation of thromboemboli has been associated with plaque instability and intraplaque hemorrhage. These features of the lesion could be influenced by the fragility and position of neovessels within the plaque. The purpose of this study was to determine whether any association exists between neovessel density, position, morphology, and thromboembolic sequelae. METHODS: Carotid endarterectomy samples were collected from 15 asymptomatic patients with greater than 80% stenoses and from 13 highly symptomatic patients who had suffered ipsilateral carotid stenotic events within 1 month of surgery. Both groups were matched for gender, age, risk factors, degree of carotid artery stenosis, and plaque size. Samples were stained with hematoxylin/eosin and van Geison. Immunohistochemistry was performed by using an endothelial specific antibody to CD31. Plaques were assessed for histologic characteristics, and neovessels were counted and characterized by size, site, and shape. RESULTS: There were significantly more neovessels in plaques (P <.00001) and fibrous caps (P <.0001) in symptomatic compared with asymptomatic plaques. Neovessels in symptomatic plaques were larger (P <.004) and more irregular. There was a significant increase in plaque necrosis and rupture in symptomatic plaques. Plaque hemorrhage and rupture were associated with more neovessels within the plaque (P <.017, P <.001) and within the fibrous cap (P <.046, P <.004). Patients with preoperative and intraoperative embolization had significantly more plaque and fibrous cap neovessels (P <.025, P <.001). CONCLUSION: Symptomatic carotid disease is associated with increased neovascularization within the atherosclerotic plaque and fibrous cap. These vessels are larger and more irregular and may contribute to plaque instability and the onset of thromboembolic sequelae.     

Cerebral Ischemic Disease and Morphometric Analyses of Carotid Plaques

Atherosclerotic carotid plaque morphology and especially, intraplaque hemorrhage are assumed to be related to neurological symptoms. Most researchers have only investigated the incidence of intraplaque hemorrhage in symptomatic and asymptomatic patients. In the present study, the amount of intraplaque hemorrhage is determined in carotid endarterectomy specimens from 33 symptomatic and 14 asymptomatic patients that caused >70% luminal stenosis. The plaque components (fibrosis, lipids, intraplaque hemorrhage, calcification, and intraluminal thrombosis) were quantified as a percentage of the total plaque volume. A high incidence of intraplaque hemorrhage was found in both the symptomatic (94%, 31/33) and asymptomatic (71%, 10/14) patients. The amount of intraplaque hemorrhage was very small within the plaques of the symptomatic (0.39% +/- 0.70%) and asymptomatic (0.37% +/- 1.12%) patients. The plaques of the symptomatic patients contained more fibrosis than lipids (45.62% +/- 14.99% and 20.45% +/- 21.45%, respectively), as did the plaques of the asymptomatic patients (42. 51% +/- 15.28% and 15.46% +/- 15.22%, respectively). Finally, intraluminal thrombosis and calcification were rare. We conclude that the amount of intraplaque hemorrhage was very small and therefore question its direct role in the development of neurological symptoms. In general, the "unstable" plaque contained more fibrosis than lipids.     

Angiogenesis in carotid atherosclerotic lesions is associated with timing of ischemic neurological events and presence of computed tomographic cerebral infarction in the ipsilateral cerebral hemisphere

We studied the association between plaque vascularity, timing of neurological and ocular symptoms, and presence of cerebral infarction in the ipsilateral cerebral hemisphere on preoperative computed tomographic (CT) scan. Consecutive patients undergoing carotid endarterectomy for carotid stenosis were included. All patients underwent preoperative noncontrast cerebral CT. Histological sections were obtained from carotid endarterectomy specimens and stained with an endothelial cell marker (CD34). Microvessel counts were performed in CD34-stained sections and verified through computerized image analysis. Associations between microvessel density in carotid atherosclerotic plaques, preoperative ipsilateral CT evidence of cerebral infarction, and timing of ipsilateral neurological and ocular events were assessed. Seventy-three patients underwent carotid endarterectomy, of whom 17 were symptomatic within 30 days of carotid endarterectomy, 11 were asymptomatic, and a further 45 had a preoperative symptom-free interval of 31-540 days (median = 56). Eighteen patients (24.6%) had CT evidence of cerebral infarction. Significantly higher microvessel counts were observed in patients with CT evidence of cerebral infarction in the appropriate hemisphere compared with patients who did not (p = 0.02). There was an inverse relationship between the microvessel density in atherosclerotic lesions and the timing of ischemic neurological events (odds ratio [OR] = 4.63, 95% confidence interval [CI] 2.95-7.28, p < 0.001). This relationship was independent of patient age (OR = 1.03, 95% CI 0.55-1.99, p = 0.70), sex (OR = 1.18, 95% CI 0.47-2.05, p = 0.56), smoking (OR = 1.07, 95% CI 0.54-2.09, p = 0.84), diabetes (OR = 0.90, 95% CI 0.45-1.79, p = 0.76), and hypercholesterolemia (OR = 0.98, 95% CI 0.68-1.11, p = 0.88). This study confirms the relationship between angiogenesis in carotid atherosclerotic lesions and development and chronology of ipsilateral hemispheric neurological events.     

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.     

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.     

The association of platelet-derived growth factor receptor expression, plaque morphology and histological features with symptoms in carotid atherosclerosis

Platelet-derived growth factor may influence smooth muscle cell migration and proliferation and, therefore, carotid plaque composition and stenosis. Platelet-derived growth factor receptor expression and histological features were compared in carotid plaques from symptomatic and asymptomatic patients. Immunocytochemistry and histology determined platelet-derived growth factor-alpha and -beta receptor expression, white blood cell infiltration, smooth muscle cell, elastin, cholesterol, collagen and intraplaque haemorrhage in carotid artery plaques removed at surgery or the post-mortem. Plaques with > 70% stenosis from asymptomatic (n = 10) and symptomatic patients (n = 27) had higher expression of platelet-derived growth factor and beta receptors and higher scores for macrophages and intraplaque haemorrhage than plaques with < 70% stenosis from asymptomatic patients (n = 33). Plaques with > 70% stenosis from symptomatic patients had significantly lower alpha receptor expression than plaques with > 70% stenosis from asymptomatic patients. The reduction of alpha receptor expression, which may inhibit smooth muscle cell migration, suggests that differential expression of platelet-derived growth factor receptor subunits in plaques may be related to symptoms.     

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.     

Carotid artery disease: the influence of diabetes mellitus

Patients with diabetes mellitus are more prone to stroke than non-diabetic patients. Using Duplex ultrasound imaging of the carotid bifurcation, we have found it possible to classify atherosclerotic plaques into four groups which appear to reflect the plaque pathology. Using this classification we have found that diabetics and non-diabetics have similar ultrasound plaque type distributions in symptomatic patients. Further subdivision of the diabetic patients on the basis of their mode of diabetic control has shown that insulin treated diabetics tend to show little evidence of intraplaque haemorrhage and ulceration. These features suggest that factors other than atherosclerosis at the carotid bifurcation may be responsible for the increased stroke risk in diabetic patients. Diabetic microangiopathy and reduced vessel compliance due to medial calcification have been suggested as possible factors. Insulin treatment of diabetics may protect against the development of occlusive atherosclerosis.     

Carotid artery atheroma: ultrasound appearance in symptomatic and asymptomatic vessels

The distribution of carotid plaque ultrasound appearance has been evaluated using duplex ultrasound in symptomatic and asymptomatic patients. There were 134 patients with unilateral carotid territory symptoms who subsequently underwent endarterectomy of the symptomatic carotid bifurcation, and 92 asymptomatic patients. Both carotid bifurcations in all patients were examined, thus providing three groups of vessels for study: (i) asymptomatic vessels in asymptomatic patients (n = 184); (ii) asymptomatic vessels in symptomatic patients (n = 134); and (iii) asymptomatic contralateral vessels in symptomatic patients (n = 134). Ultrasound appearances were classified as types 1-4. This classification has previously been compared prospectively with endarterectomy specimen pathology where the more echolucent type 1 and 2 lesions correlated well with the presence of intraplaque haemorrhage or ulceration. In the symptomatic arteries, type 1 and 2 lesions were predominant, whereas in the asymptomatic patients the most common lesions were types 3 and 4. This difference was statistically significant (P less than 0.01). Evaluation of the asymptomatic contralateral vessel in the symptomatic patients showed a pattern of plaque type distribution between the other two groups.     

Carotid intraplaque hemorrhage detected by magnetic resonance imaging predicts embolization during carotid endarterectomy

BACKGROUND: Microembolization detected during the dissection phase of carotid endarterectomy (CEA) is associated with plaque instability and might be associated with perioperative morbidity. Intraplaque hemorrhage is found in unstable plaques and is detectable using magnetic resonance imaging (MRI). We aimed to ascertain whether intraplaque hemorrhage as seen on carotid MRI predicts particulate embolization in the dissection phase of CEA. METHODS: Patients with high-grade symptomatic carotid stenosis undergoing CEA were prospectively enrolled. All underwent preoperative MRI assessment of the carotid arteries for intraplaque hemorrhage and transcranial Doppler scanning during the dissection phase of the CEA to assess the presence of microembolic signals. Associations between intraplaque hemorrhage and intraoperative microembolic signals were studied. RESULTS: Analysis was undertaken on 60 participants; of these, 36 (60%) showed ipsilateral carotid MRI intraplaque hemorrhage, and 24 (40%) did not. Microembolic signals were detected during the dissection phase in 23 (38.3%) participants, and 19 had MRI-detected intraplaque hemorrhage. The association between carotid intraplaque hemorrhage and the presence of dissection phase microembolic signals was significant (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.6 to 19.7, P = .007), even after controlling for age, sex, individual surgeon, degree of stenosis, and delay from symptom to CEA (adjusted OR, 5.8; 95% CI, 1.1 to 30.4, P = .037). CONCLUSION: Intraplaque hemorrhage as detected by carotid MRI predicts particulate embolization during the dissection phase of CEA. This imaging technique can be used to identify patients with increased intraoperative thromboembolic risk, and this could influence preventive strategies.     

B-mode ultrasonographic characterization of carotid atherosclerotic plaques in symptomatic and asymptomatic patients

OBJECTIVE: To identify features on B-mode ultrasonography (US) prevalent in symptomatic plaques and correlate these findings with histopathologic markers of plaque instability. METHODS: Carotid endarterectomy (CEA) plaques from symptomatic and asymptomatic patients with critical stenoses (>70%) were qualitatively assessed using preoperative B-mode US for echolucency and calcific acoustic shadowing. US echolucency was quantitated ex vivo using computerized techniques for gray-scale median (GSM) analysis. Histopathologic correlates for US plaque echolucency (percentage of necrotic core area) and acoustic shadowing (percentage of calcification area) were determined. RESULTS: Fifty CEA plaques were collected from 48 patients (46 unilateral and two bilateral); 26 of these plaques were from symptomatic patients. Age, degree of stenosis, and atherosclerotic risk factors were similar for the symptomatic and asymptomatic patients. Using preoperative B-mode US, 58%, 35%, and 7% of symptomatic plaques and 18%, 41%, and 41% of asymptomatic plaques were found to be echolucent, echogenic, and calcific, respectively (P < .05). Using ex-vivo B-mode US and GSM analysis, symptomatic plaques were more echolucent (41 +/- 19) than asymptomatic plaques (60 +/- 13), P < .03. A strong inverse correlation was found between the percent plaque necrotic area core and GSM (R = -0.9, P < .001). Percentage of calcification area in plaques with acoustic shadowing was 66% and only 27% in those without acoustic shadowing (P < .05). CONCLUSIONS: Using B-mode US, symptomatic plaques are more echolucent and less calcified than asymptomatic plaques and are associated with a greater degree of histopathologic plaque necrosis. Such features are indicative of plaque instability and should be considered in the decision-making algorithm when selecting patients with high-grade asymptomatic carotid stenosis for intervention.     

Noninvasive Identification of the Unstable Carotid Plaque

Intraplaque hemorrhage, enlarging lipid cores, and their proximity to the flow lumen are important determinants of carotid plaque rupture and neurological complications. We developed an image-analysis method for B-mode ultrasound, pixel distribution analysis (PDA), for preprocedural identification of these high-risk features in carotid plaques. This technique may improve selection of patients for carotid endarterectomy and carotid artery stenting. Forty-two patients with high-grade carotid stenosis in 45 arteries, 18 symptomatic and 27 asymptomatic, underwent preoperative ultrasound. Intraplaque hemorrhage, lipid, fibromuscular tissue, calcium, lipid core area, and distance from the flow lumen were quantified using pixel intensities of tissues in control subjects. These findings were contrasted between symptomatic and asymptomatic plaques and correlated with histology. Inter- and intraobserver variabilities were determined for this technique. Pixel intensities of control tissues were discrete and significantly different from each other (median: blood 0, lipid 27, muscle 45.5, fibrous tissue 204, and calcium 245). There was more intraplaque hemorrhage (p < 0.001) and lipid (p = 0.002) but less calcium (p < 0.001) within symptomatic plaques. Lipid cores were larger (p = 0.005) and their distance from the flow lumen was lower (p = 0.01) in symptomatic plaques. Intraplaque hemorrhage, lipid, fibromuscular tissue, calcium, lipid core size, and distance from flow lumen measured by PDA correlated with histology. No significant inter- or intraobserver variabilities were observed in these measurements. PDA accurately identified more intraplaque hemorrhage and lipid, less calcium, and larger lipid cores located closer to the flow lumen in symptomatic patients with carotid stenosis. These data indicate that PDA may be used to identify high-risk carotid atherosclerotic plaques and thereby improve the selection of patients requiring treatment.     

Carotid plaque histology using real-time ultrasonography: Clinical and therapeutic implications

To evaluate the ability of ultrasonographic imaging to detect plaque hemorrhage in carotid atheroma, a study was undertaken that compared pathologic findings to preoperative ultrasonographic findings. Ultrasonography identified two plaque categories based on the heterogeneous and homogeneous echo patterns of the lesions studied. Heterogeneous lesions accounted for 91 percent of intraplaque hemorrhages (30 of 33) and 100 percent of ulcerated lesions (15 of 15). In 41 of 50 specimens (82 percent), ultrasonography correctly identified the presence or absence of plaque hemorrhage. False-negative studies (3 of 50) were due to the minute foci of remote hemorrhages. False-positive studies (6 of 50) resulted from plaques that contained large amounts of lipid or cholesterol.Preoperative ultrasound carotid imaging can be used to detect the histologic characteristics of plaque. Since recent clinicopathologic studies have implicated intraplaque hemorrhage and ulceration in symptomatic carotid disease, this information may be of value in choosing therapy, especially for the asymptomatic patient.     

Multidetector-row computed tomography in evaluation of atherosclerotic carotid plaques complicated with intraplaque hemorrhage

Our aim was to determine the sensitivity and specificity of multidetector-row computed tomography (CT) in detecting atherosclerotic carotid plaques complicated with intraplaque hemorrhage. We examined carotid plaques from 31 patients operated for carotid artery stenosis. Results of preoperative multidetector-row CT analysis of carotid plaques were compared with results of histological analysis of the same plaque areas. Carotid endarterectomy was performed within 1 week of multidetector-row CT. American Heart Association classification of atherosclerotic plaques was applied for histological classification. Median tissue density of carotid plaques complicated with intraplaque hemorrhage was 22 Hounsfield units (HU). Median tissue density of noncalcified segments of uncomplicated plaques was 59 HU (p=0.0062). The highest tissue density observed for complicated plaques was 31 HU. Multidetector-row CT detected plaques complicated with hemorrhage with sensitivity of 100% and specificity of 64.7%, with tissue density of 31 HU as a threshold value. Multidetector-row CT showed a high level of sensitivity and a moderate level of specificity in detecting atherosclerotic carotid plaques complicated with hemorrhage.     

Atherosclerotic plaque rupture and intraplaque hemorrhage do not correlate with symptoms in carotid artery stenosis

OBJECTIVE: Previously we failed to demonstrate a correlation between plaque type and symptoms in 165 carotid endarterectomy specimens. The purpose of this study was to analyze the relation between the anatomy of the carotid plaques and the presence of symptoms in 281 carotid endarterectomy specimens. METHODS: The patients were 213 men (mean age, 68 years) and 68 women (mean age, 68.7 years), with symptomatic disease (n = 133) or asymptomatic disease (n = 148). Specimens were processed for histologic analysis and immunohistochemistry. RESULTS: Plaques were categorized as complicated or noncomplicated, and ruptured or nonruptured. Risk factors could not be correlated with any pathologic or immunohistochemical findings or between plaque type and clinical symptoms. CONCLUSIONS: Almost 70% of plaque specimens demonstrated thrombus, intraplaque hemorrhage, or both. Thrombosis was observed in one fourth of specimens, and intraplaque hemorrhage in almost two thirds of specimens. Sixty four percent of plaques demonstrated neovascularization. It was not possible to demonstrate that complicated plaques (plaque rupture, thrombosis, intraplaque hemorrhage) are associated with symptoms, and it appears that such plaques may occur at any time, irrespective of symptoms.     

Cerebral white matter hyperintense lesions are associated with unstable carotid plaques.

OBJECTIVES: The aim of this study was to determine whether unstable carotid plaques, a known risk factor for cerebral emboli, are associated with cerebral white matter lesions. METHODS: Seventy-one symptomatic patients undergoing magnetic resonance imaging prior to carotid endarterectomy for high grade carotid stenosis were included in this study. The number and volume of white matter hyperintense lesions (WMHL) on fluid attenuated inversion recovery brain scans were compared according to the morphology of carotid plaque based upon the American Heart Association (AHA) histological classification. RESULTS: Of the 57 patients who had good quality brain scans and non-fragmented carotid plaques, 15 plaques were defined as stable (type V) and 42 as unstable (type VI). After adjustment for the major risk factors affecting WMHL, unstable carotid plaques were found to be associated with more WMHL in the ipsilateral cerebral hemisphere than stable plaques (transformed means 2.50+/-1.2 vs. 1.53+/-1.1, p=0.016), however, there was only a trend towards larger WMHL volumes (p=0.079). CONCLUSIONS: The observed association between unstable carotid plaques and the number of white matter lesions suggest that thromboembolic plaque activity may contribute to the development of leukoaraiosis, in particular smaller individual lesions. Larger studies are warranted to confirm this finding and explore the potential clinical impact for selecting candidates for carotid endarterectomy.