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Biomedical subjects

M S Ferguson

Publications and source records attributed to M S Ferguson.

13 recordsLinked to original sources

Metastasizing pleomorphic salivary adenoma.

OBJECTIVE: To address questions about the etiology, behavior, optimal treatment, and prognosis of metastasizing pleomorphic adenoma (MPA), we undertook a review of the literature (1953-2005) and constructed a virtual series of all identified cases of MPA, metastatic lesions that are very occasionally identified in patients with a history of pleomorphic salivary adenoma and, on detailed pathological evaluation, found to exhibit all the histological hallmarks of the preceding benign lesions. DATA SOURCES: A review of the English-language literature between 1953 and 2005 using MEDLINE, secondary references identified from bibliographies of pertinent articles, and a further case from one of our institutions. DATA SYNTHESIS: A virtual case series was constructed and quantitatively analyzed. Forty-two patients with an average age of 33 years were identified. There were 20 male and 22 female patients. There was an overwhelming history of incomplete surgery for pleomorphic salivary adenoma. Most patients had locoregional recurrences before metastasis, and the mean presentation-to-metastasis latency was 16 years. Bone was the most common site for metastases (45%), followed by the head and neck (43%) and lung (36%). There was significant morbidity and mortality from distant disease, with 5-year disease-specific and disease-free survival of 58% and 50%, respectively. Developing distant lesions within 10 years of the primary tumor and presence of metastases in multiple sites were independent predictors of survival on Cox regression analysis. Metastasectomy conferred significant survival advantage over nonoperative treatment (log-rank analysis, P<.02). Chemotherapy and radiotherapy were of limited value. CONCLUSIONS: Meticulous surgery is crucial in preventing MPA. Metastatic disease carries significant morbidity and mortality and should be treated surgically when feasible.

Adenoma, Pleomorphic↗

Differentiation of intraplaque versus juxtaluminal hemorrhage/thrombus in advanced human carotid atherosclerotic lesions by in vivo magnetic resonance imaging.

BACKGROUND: Intraplaque hemorrhage and juxtaluminal hemorrhage/thrombus may differ in cause and clinical implications. This study tested the hypothesis that MRI can distinguish between intraplaque hemorrhage and juxtaluminal hemorrhage/thrombus and investigated the association between hemorrhage and underlying lesion types. METHODS AND RESULTS: Twenty-six patients scheduled for carotid endarterectomy were imaged with a 1.5-T GE scanner by a multicontrast-weighted MRI technique. Hemorrhages were identified with previously established MRI criteria, and differentiations were made between intraplaque and juxtaluminal hemorrhage/thrombus. Corresponding histology was used to confirm the magnetic resonance findings. Tissues underlying areas of hemorrhage/thrombus were histologically categorized according to modified American Heart Association criteria. Of 190 matched sections, 140 contained areas of hemorrhage by histology, of which MRI correctly detected 134. The sensitivity and specificity for MRI to correctly identify cross sections that contained hemorrhage were 96% and 82%, respectively. Furthermore, MRI was able to distinguish juxtaluminal hemorrhage/thrombus from intraplaque hemorrhage with an accuracy of 96%. The distribution of lesion types underlying hemorrhages differed significantly (P=0.004). Intraplaque hemorrhage had an underlying lipid-rich type IV/V lesion in 55% of histological sections, whereas juxtaluminal hemorrhage/thrombus had an underlying calcified lesion type VII in 70% of sections. CONCLUSIONS: In vivo high-resolution MRI can detect and differentiate intraplaque hemorrhage from juxtaluminal hemorrhage/thrombus with good accuracy. The association of hemorrhage and lesion types suggests potential differences in origin. Noninvasive MRI therefore provides a possible tool for prospectively studying differences in origin of plaque hemorrhage and the association of plaque progression and instability.

Carotid Artery Diseases↗

Quantitative evaluation of carotid plaque composition by in vivo MRI.

OBJECTIVE: This study evaluates the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo. METHODS AND RESULTS: Thirty-one subjects scheduled for carotid endarterectomy were imaged with a 1.5T scanner using time-of-flight-, T1-, proton density-, and T2-weighted images. A total of 214 MR imaging locations were matched to corresponding histology sections. For MRI and histology, area measurements of the major plaque components such as lipid-rich/necrotic core (LR/NC), calcification, loose matrix, and dense (fibrous) tissue were recorded as percentages of the total wall area. Intraclass correlation coefficients (ICCs) were computed to determine intrareader and inter-reader reproducibility. MRI measurements of plaque composition were statistically equivalent to those of histology for the LR/NC (23.7 versus 20.3%; P=0.1), loose matrix (5.1 versus 6.3%; P=0.1), and dense (fibrous) tissue (66.3% versus 64%; P=0.4). Calcification differed significantly when measured as a percentage of wall area (9.4 versus 5%; P<0.001). Intrareader and inter-reader reproducibility was good to excellent for all tissue components, with ICCs ranging from 0.73 to 0.95. CONCLUSIONS: MRI-based tissue quantification is accurate and reproducible. This application can be used in therapeutic clinical trials and in prospective longitudinal studies to examine carotid atherosclerotic plaque progression and regression.

Aged↗

In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques.

BACKGROUND: High-resolution MRI has been shown to be capable of identifying plaque constituents, such as the necrotic core and intraplaque hemorrhage, in human carotid atherosclerosis. The purpose of this study was to evaluate differential contrast-weighted images, specifically a multispectral MR technique, to improve the accuracy of identifying the lipid-rich necrotic core and acute intraplaque hemorrhage in vivo. METHODS AND RESULTS: Eighteen patients scheduled for carotid endarterectomy underwent a preoperative carotid MRI examination in a 1.5-T GE Signa scanner using a protocol that generated 4 contrast weightings (T1, T2, proton density, and 3D time of flight). MR images of the vessel wall were examined for the presence of a lipid-rich necrotic core and/or intraplaque hemorrhage. Ninety cross sections were compared with matched histological sections of the excised specimen in a double-blinded fashion. Overall accuracy (95% CI) of multispectral MRI was 87% (80% to 94%), sensitivity was 85% (78% to 92%), and specificity was 92% (86% to 98%). There was good agreement between MRI and histological findings, with a value of kappa=0.69 (0.53 to 0.85). CONCLUSIONS: Multispectral MRI can identify the lipid-rich necrotic core in human carotid atherosclerosis in vivo with high sensitivity and specificity. This MRI technique provides a noninvasive tool to study the pathogenesis and natural history of carotid atherosclerosis. Furthermore, it will permit a direct assessment of the effect of pharmacological therapy, such as aggressive lipid lowering, on plaque lipid composition.

Carotid Arteries↗

Mechanisms of anterior cruciate ligament neovascularization and ligamentization.

Columbia-Rambouillet cross-bred sheep were used to study the revascularization and ligamentization process of anterior cruciate ligament (ACL) reconstruction over a 6-month period using basic histology, immunohistochemistry, and electron microscopy. The reconstruction technique studied was a quadruple-hamstring, interference screw fixation technique. Further, these specimens, after retrieval at 6, 12, and 26 weeks, were compared with human arthroscopic 'second looks' and with 10 en bloc specimens obtained when a cruciate-sacrificing total knee replacement was performed. The study showed that, with this reconstruction technique, Sharpey's fibers were seen at 6 weeks in both sheep and human specimens. The intratunnel specimens showed proliferative chondrification, then ossification of the matrix. Intra-articular neovascularization, ligamentization, and junction ossification occurred. Myoblasts or smooth muscle cells appear to mediate the ligamentization as evidenced in electron microscopy by proliferate collagen manufacture. These myoblasts were seen in both the healing sheep and human second looks, but not seen in mature ACL grafts or in normal ACLs. At 6 months postoperatively, the sheep ACL reconstruction appeared clinically, histologically, and immunohistochemically indistinguishable from the normal sheep ACL. A correlation of this work with published animal studies in which biomechanical testing was performed and with human 'second looks' would imply that an ACL reconstruction may be vulnerable during this period of neovascularization and ligamentization.

Adult↗

Carotid plaque morphology and clinical events.

BACKGROUND AND PURPOSE: Studies have suggested that B-mode ultrasonography can be used to determine carotid plaque composition and that specific plaque characteristics are associated with a worse clinical outcome. However, histological studies examining the relationship between carotid plaque morphology and clinical outcome have reported conflicting findings. Furthermore, few investigators have described plaque morphology in quantifiable terms. This study examines the association between the volume of carotid plaque constituents and preoperative ischemic neurological symptoms. Constituents examined were chosen based on their potential for identification by current diagnostic imaging modalities such as ultrasound or MRI. METHODS: Atherosclerotic plaques from 43 patients undergoing carotid endarterectomy were examined histologically, with sections obtained every 0.5 to 1 mm. The lesions were examined for the presence and quantity of fibrous intimal tissue, intraplaque hemorrhage, lipid core, necrotic plaque core, and calcification. The quantity of each constituent was compared in plaques removed from symptomatic patients with those excised from asymptomatic individuals. Differences were analyzed with a Kolmogorov-Smirnov statistic. RESULTS: There was no difference between plaques removed from asymptomatic and symptomatic patients with regard to the presence and volume of fibrous intimal tissue, intraplaque hemorrhage, the lipid core, the necrotic core, or calcification. CONCLUSIONS: In patients with highly stenotic carotid lesions who are undergoing carotid endarterectomy, gross plaque composition is similar regardless of preoperative symptom status. Given this similarity, it is unlikely that differences in the volume of intraplaque hemorrhage, lipid core, necrotic core, or calcification in atherosclerotic carotid plaques explain their embolic history.

Aged↗

A new method for studying plaque morphology.

A histologic method was developed for three-dimensional (3-D) analysis of atherosclerotic plaques removed from the carotid bifurcation during endarterectomy. By sectioning the plaque at frequent intervals (0.5 to 1.0 mm), it is possible to obtain important information on plaque constituents with regard to their volume and distribution within the lesion. These data from each section are combined with those from other sections and displayed in a 3-D format for the entire length of the lesion. The tissues making up each of the 10 carotid plaques were outlined and digitized for each histologic section by position along the lesion. From the areas outlined a 3-D model was created by a computer-aided design program. Quantitative information on tissue distribution within the plaque was measured. Fibrous tissue constituted between 35% and 70% of plaque volume; loose necrosis from 0.5% to 30% of the plaque and thrombus occupied, at a maximum, 10% even though if was present in six of the 10 plaques. To investigate the distribution of constituents about the long axis, measurements were also made from each of the four quadrants of each section. The reproducibility of the measurements of three sets of sections at 10-mm separation showed that estimates of the amount of some constituents were very reproducible whereas others had considerable variation related to the small volume they occupied within the lesion. By generating a complete 3-D reproduction of the contents of atherosclerotic plaques, it may be possible to identify those features of the plaque that are most responsible for the development of ischemic events.

Arteriosclerosis↗

Echolucent regions in carotid plaque: preliminary analysis comparing three-dimensional histologic reconstructions to sonographic findings.

This study compares sonographic and histologic findings within defined spatial regions in carotid artery plaque, using computer generated three-dimensional reconstructions. Twenty-four patients (14 asymptomatic, 10 symptomatic) with angiographically documented 70% to 99% carotid artery stenosis were examined with ultrasonic B-mode imaging prior to endarterectomy. Using a standardized protocol for instrument set-up and scanning technique, echolucent regions in the plaque were identified. After endarterectomy, each plaque was sectioned at 0.5 to 1.0 millimeter increments throughout its length. Sites containing intraplaque hemorrhage, cholesterol clefts, foam cells, necrotic cores, dense calcification and speckled calcification were identified. These areas were outlined on a template, digitized and imported into a computer program that created three-dimensional reconstructions of the histologic findings. Each carotid plaque was divided into quadrants for analysis: (1) lateral wall proximal to the common carotid bifurcation (flow divider); (2) medial wall proximal to the flow divider; (3) lateral wall distal to the flow divider; and (4) medial wall distal to the flow divider. The odds of finding intraplaque hemorrhage, foam cells, necrotic cores and speckled calcification were significantly higher in quadrants with an echolucent region identified by ultrasonography (odds ratio (95% confidence interval) for intraplaque hemorrhage = 3.5 (1.4-8.6); foam cells = 4.0 (1.6-9.9); necrotic cores = 3.2 (1.2-8.4); speckled calcification = 4.0 (1.6-9.8). This preliminary analysis demonstrates the potential of these newly developed techniques for comparing ultrasonic imaging to histology.

Aged↗

Carotid artery intraplaque hemorrhage and stenotic velocity.

BACKGROUND AND PURPOSE: One of the proposed mechanisms for sudden expansion of a carotid bifurcation plaque is hemorrhage within the lesion. It has been postulated that the sudden increase in plaque size will acutely reduce blood flow to the ipsilateral hemisphere and induce either a transient ischemic attack or a stroke. In this study, the relation between peak systolic velocity at the site of narrowing and its potential role in the development of intraplaque hemorrhage were investigated. METHODS: Ten patients who had carotid endarterectomy were examined by duplex Doppler sonography before surgery to determine the peak systolic velocity at the site of maximal narrowing. The excised carotid plaques were sectioned at 1-mm intervals and examined for histological evidence of intraplaque hemorrhage. The recorded peak systolic velocities in patients with intraplaque hemorrhage were compared with the velocities in cases in which no hemorrhage was identified. RESULTS: Five of the ten patients had intraplaque hemorrhage. Four of the five patients with intraplaque hemorrhage had a peak systolic velocity of > 420 cm/sec and diastolic velocities of > 160 cm/sec; none of the patients without intraplaque hemorrhage had such high values. CONCLUSIONS: Peak systolic velocity is significantly higher in patients with intraplaque hemorrhage. The specificity and sensitivity of a peak systolic velocity of > 420 cm/sec in predicting intraplaque hemorrhage remains to be determined.

Arteriosclerosis↗

Techniques for high-resolution MR imaging of atherosclerotic plaque.

Atherosclerotic cardiovascular disease is the most common cause of death in the United States. Investigation of atherosclerotic plaque morphology and composition is important because the findings may be useful in predicting prognosis or response to therapy. This study presents high-resolution magnetic resonance (MR) imaging techniques developed on a 1.5-T whole-body imager with a custom-built surface coil, for characterizing the composition and morphology of plaque removed at carotid endarterectomy. The initial comparison of MR imaging and histologic results showed good correlation. In conjunction with MR angiography, these techniques could be used in in vivo imaging to define the size, location, and contents of atherosclerotic plaque at the carotid bifurcation.

Artifacts↗

Phased-array magnetic resonance imaging of the carotid artery bifurcation: preliminary results in healthy volunteers and a patient with atherosclerotic disease.

A high resolution MR imaging technique using a custom designed flexible phased-array surface coil was developed to examine the wall of the carotid artery bifurcation in vivo. The phased-array consisted of two overlapping coils which increased the image signal-to-noise ratio at the depth of the carotid artery by approximately 70%, relative to a similarly sized single loop coil. The imaging protocol included a 2D T1-weighted (T1W) spin-echo scan and cardiac gated T2-weighted and proton density-weighted (PDW) fast spin-echo (FSE) scans. Images were obtained of six healthy volunteers and of one patient with known atherosclerotic disease several days before carotid endarterectomy. On T1W and PDW images of the healthy volunteers, the carotid arterial wall appeared to be comprised of two concentric rings; a high signal inner ring and a lower signal outer ring. The MR images of the patient revealed a calcified carotid bifurcation plaque which was confirmed during surgery. The endarterectomy specimen was imaged in vitro with MR and then sectioned histologically for correlation with the patients in vivo images. Our preliminary findings indicate that a high resolution technique may provide a noninvasive technique to study atherosclerosis of the carotid bifurcation.

Arteriosclerosis↗

Atherosclerosis of the carotid artery: evaluation by magnetic resonance angiography.

Carotid artery atherosclerotic plaques (APs) can lead to brain ischemia, an event shown to correlate with both the degree of stenosis and the composition of the AP. Currently, accurate estimates of stenosis can be obtained by either x-ray angiography or three-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA). Our purpose was to determine whether three-dimensional TOF MRA images could also provide information on plaque location, morphology, and composition. Seven pre-endarterectomy patients underwent three-dimensional TOF MRA. After endarterectomy, plaque histology was evaluated. Three-dimensional TOF MRA images contained sufficient soft tissue contrast to differentiate the plaques from the surrounding tissues in all cases. Estimation of plaque morphology had 80% correlation with histology. Finally, intraplaque hemorrhage and calcification were deplicted as regions of moderately high and very low intensity, respectively. These preliminary results suggest that three-dimensional TOF MRA may be useful in studying the development and progression of carotid atherosclerosis.

Aged↗

Characterization of atherosclerotic plaques at the carotid bifurcation: correlation of high-resolution MR imaging with histologic analysis--preliminary study.

The clinical symptoms and morbidity that result from carotid artery disease, the primary cause of stroke, are mainly due to plaque ulceration, thrombosis, intraplaque hemorrhage, and thinned fibrous caps. The contents of atherosclerotic plaques of the carotid artery can be determined with in vivo high-resolution magnetic resonance imaging with flow suppression. Eight patients scheduled to undergo endarterectomy and four healthy volunteers were imaged with a 1.5-T imager and custom-made carotid phased-array coils. T1-weighted spin-echo images and cardiac-gated proton-density--weighted fast spin-echo images were acquired. In vivo imaging findings as determined by three radiologists were correlated with ex vivo imaging and histologic findings. Among the eight plaque specimens, regions of hemorrhage, calcium, lipid deposits, and fibrous plaques were identified on T1- and proton-density-weighted images. Calcium and lipid deposits were detectable on both T1- and proton-density--weighted images. Hemorrhage and fibrous plaques were better demonstrated on proton-density--weighted images.

Adult↗