A fluorescence lifetime spectroscopy study of matrix metalloproteinases-2 and -9 in human atherosclerotic plaque.

Matrix metalloproteinase (MMP)-2 and -9 play important roles in the progression of atherosclerosis. This study aims to determine whether MMP-2 and -9 content in the fibrotic caps of atherosclerotic plaque is correlated with plaque autofluorescence. A time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) system was used to measure the autofluorescence and assess the biochemical composition of human plaques obtained from carotid endarterectomy. Results presented here demonstrate for the first time the ability to characterize the biochemical composition as it relates to MMP-2 and -9 content in the atherosclerotic plaque cap using a label-free imaging technique implemented with a fiberoptic TR-LIFS system.

Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy.

OBJECTIVE: Plaque with dense inflammatory cells, including macrophages, thin fibrous cap and superficial necrotic/lipid core is thought to be prone-to-rupture. We report a time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) technique for detection of such markers of plaque vulnerability in human plaques. METHODS: The autofluorescence of carotid plaques (65 endarterectomy patients) induced by a pulsed laser (337 nm, 0.7 ns) was measured from 831 distinct areas. The emission was resolved spectrally (360-550 nm range) and temporally (0.3 ns resolution) using a prototype fiber-optic TR-LIFS apparatus. Lesions were evaluated microscopically and quantified as to the % of different components (fibrous cap, necrotic core, inflammatory cells, foam cells, mature and degraded collagen, elastic fibers, calcification, and smooth muscle cell of the vessel wall). RESULTS: We determined that the spectral intensities and time-dependent parameters at discrete emission wavelengths (1) allow for discrimination (sensitivity >81%, specificity >94%) of various compositional and pathological features associated with plaque vulnerability including infiltration of macrophages into intima and necrotic/lipid core under a thin fibrous cap, and (2) show a linear correlation with plaque biochemical content: elastin (P<0.008), collagen (P<0.02), inflammatory cells (P<0.003), necrosis (P<0.004). CONCLUSION: Our results demonstrate the feasibility of TR-LIFS as a method for the identification of markers of plaque vulnerability. Current findings enable future development of TR-LIFS-based clinical devices for rapid investigation of atherosclerotic plaques and detection of those at high-risk.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions.

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Innominate artery occlusive disease: sonographic findings.

OBJECTIVE: The objective of this study was to report the sonographic abnormalities in a group of patients with angiographically proven innominate artery stenosis and occlusion. MATERIALS AND METHODS: A review of all cerebrovascular sonograms at our institutions was undertaken to identify patients with complete or partial flow reversal in the right vertebral artery and reversal or midsystolic deceleration of flow in any one of the three major segments of the right carotid system (common, internal, or external carotid artery). The distribution and appearance of these abnormalities was evaluated, and the presence or absence of tardus-parvus waveforms was noted in any segment of the right carotid artery. Additionally, a left to right common carotid peak systolic velocity ratio (LCCA/RCCA) was calculated and compared to published normal values. All patients had correlative contrast or MR angiography. Correlation was made between the severity of stenosis as determined by angiographic images and waveform aberrations as well as the more objective LCCA/RCCA ratios. RESULTS: Twelve patients were identified as having the abnormalities described above in the right vertebral and carotid arteries. Doppler waveforms from the right vertebral artery revealed that eight of the 12 patients had complete reversal of flow at rest. Bidirectional flow was found in the remaining four as manifested by the presence of marked midsystolic deceleration. In the carotid arteries, one patient had complete reversal of flow in all segments of the right carotid system. Waveforms with midsystolic deceleration were identified in at least one of the carotid arteries of the remaining 11 patients: common carotid artery (8/11 = 73%), internal carotid artery (10/11 = 91%), external carotid artery (3/11 = 27%). The average LCCA/RCCA was 3.1 with a range of 1.7 to 5.7 (normal = 0.7-1.3). All patients had severe innominate artery disease (from 70% to occlusion) by contrast angiography or MR angiography. There was no correlation between the angiographically determined degree of stenosis and the Doppler findings. CONCLUSION: A distinctive pattern of hemodynamic alterations occurs in the right vertebral and carotid arteries of patients with severe innominate artery disease. Findings include reversed or bidirectional flow in the right vertebral artery, the presence of midsystolic deceleration in any of the branches of the right carotid system, and elevated LCCA/RCCA ratio.

In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy.

Accumulation of numerous macrophages in the fibrous cap is a key identifying feature of plaque inflammation and vulnerability. This study investigates the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a potential tool for detection of macrophage foam cells in the intima of atherosclerotic plaques. Experiments were conducted in vivo on 14 New Zealand rabbits (6 control, 8 hypercholesterolemic) following aortotomy to expose the intimal luminal surface of the aorta. Tissue autofluorescence was induced with a nitrogen pulse laser (337 nm, 1 ns). Lesions were histologically classified by the percent of collagen or macrophage foam cells as well as thickness of the intima. Using parameters derived from the time-resolved fluorescence emission of plaques, we determined that intima rich in macrophage foam cells can be distinguished from intima rich in collagen with high sensitivity (>85%) and specificity (>95%). This study demonstrates, for the first time, that a time-resolved fluorescence-based technique can differentiate and demark macrophage content versus collagen content in vivo. Our results suggest that TR-LIFS technique can be used in clinical applications for identification of inflammatory cells important in plaque formation and rupture.

Ultrasonographic confirmation of carotid artery atheromas diagnosed via panoramic radiography.

BACKGROUND: Studies have shown that panoramic radiographs can capture images of calcified atheromas in the internal carotid artery (ICA) in some neurologically asymptomatic patients receiving routine dental care. However, the prevalence of these hemodynamically significant lesions--that is, those causing greater than 50 percent vessel lumen occlusion with the consequent heightened risk of stroke--has been evaluated rarely. The purpose of this study was to use Doppler ultrasonography (DUS) to determine the prevalence of large occlusive lesions detected initially via panoramic radiography. Aggressive medical and surgical interventions directed toward these large lesions have been shown to moderate the risk of stroke. STUDY DESIGN: The authors analyzed the panoramic radiographs of 1,548 consecutively treated, neurologically asymptomatic dental patients who were 50 years or older. Those with presumptive atheromas underwent DUS for confirmation of the diagnosis and for determination of the degree of stenosis. RESULTS: The radiographs of 65 patients (4.2 percent) showed at least one ICA atheroma. Thirty-eight patients had bilateral opacities and 27 had unilateral opacities. DUS evaluation of the 103 sides of the neck with a radiographically identified atheroma revealed that none of the ICAs were normal, 81 (79 percent) had less than 50 percent stenosis, 18 (17 percent) had 50 to 69 percent stenosis and four (4 percent) had 70 percent or greater stenosis. Four of the ICAs on the 27 sides without calcifications were deemed normal and 23 had less than 50 percent stenosis. CONCLUSIONS: These results demonstrate that a subset of patients (15 [23 percent] of 65) with an occult atheroma discovered on panoramic radiography had significant (> 50 percent) levels of ICA stenosis. CLINICAL IMPLICATIONS: Dentists should refer all patients with radiographically identified atheromas to a physician for confirmation of the diagnosis and a determination of the magnitude of disease, because antiatherogenic interventions have been shown to prevent a stroke.

Cost analysis of carotid endarterectomy: is age a factor?

Carotid endarterectomy (CEA) has been demonstrated to be safe and effective in elderly patients. Our aim was to analyze and compare outcome and cost of CEA in both elderly and younger patient groups. A total of 125 consecutive patients who underwent CEA were examined retrospectively and grouped according to age (<80 years old, n = 95; and >or=80 years old, n = 30). The actual total costs and itemized costs were analyzed, and diagnosis-related group (DRG) code payor mix were identified. Patient demographics and risk factors were similar except for a greater incidence of coronary artery disease (CAD) in the >or=80 group than in these <80 (43.3% vs. 21.1%, p < 0.05). Patients had similar minor complication rates; however, the >or=80 group had higher perioperative major complications (16.7% vs. 1.1%, p < 0.01). There were no deaths and there was one perioperative stroke, which occurred in the <80 group. Mean length of stay (LOS), intensive care unit (ICU) LOS, and ICU admissions were greater in the >or=80 group. Cost figures were normalized to a base value of 10 US dollars to maintain proprietary data. Actual total costs of CEA were 131.50 US dollars for the >or=80 group and $100 for the <80 group (p < 0.001). Significant cost differences were found in ICU room costs, and costs for clinical laboratory, radiology imaging, other specialty consults, operating room, and ancillary services in the >or=80 group compared with the <80 group. These results show that the cost of CEA in the elderly is significantly greater than that for younger patients. This difference can be attributed to a greater number of major complications in the more elderly group, who require increased ICU stay, and thus require more clinical laboratory, radiology imaging, and specialty consult service resources. Consideration should be given for a DRG modifier code to increase hospital reimbursement for increased associated costs in elderly patients undergoing CEA.

Open versus endovascular repair of abdominal aortic aneurysms: what does each really cost?

Endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) has emerged as an alternative to open repair (OR). The aim of this study was to compare the clinical outcomes and specific costs of these procedures since commercialization.A retrospective analysis of 119 consecutive infrarenal AAA repaired via an EVAR or an OR between July 2000 and September 2001 was performed. Patient charts were reviewed. Diagnostic-related group (DRG) classification and payer mix were identified. The hospital cost accounting system was accessed to obtain actual variable direct cost (AVDC) for the two groups. Percentages of the mean AVDC for the two groups were compared in the following cost categories: graft, operating room, radiology procedures and supplies, pharmacy, respiratory therapy, clinical laboratories, surgical floor, and monitored unit. Hospital profit margins were determined. Fifty-five patients underwent EVAR and 64 patients underwent OR. Mean aneurysm size was 5.5A cm (EVAR) and 6.1A cm (OR). Mean intensive care unit (ICU) stay was 0.09 days for EVAR vs. 3.5 days for OR ( p < 0.05). Mean length of stay (LOS) was 1.96 days for EVAR vs. 7.3 days for OR ( p < 0.05). Reimbursement was based on DRG 110, 47.3% in the EVAR and 79.7% in the OR group ( p < 0.05), and DRG 111, 50.9% in the EVAR group and 12.5% in the OR group ( p < 0.05). The payer mix showed no significant differences between the two groups. Mean AVDC for EVAR was 1.74 times that of OR. Significant differences in the distribution of costs were found in the following: graft costs (58% vs. 6.3%, p < 0.05), radiology procedures and supplies (3.9% vs. 0.1%, p < 0.05), pharmacy (1.9% vs. 10.5%, p < 0.05), and monitored unit (7.3% vs. 24.65%, p < 0.05) comparing EVAR vs. OR, respectively. Median cost of an endovascular graft was 22.4 times that of the standard graft for OR. Average hospital profit margins for an EVAR case was 49.5% vs. 88.6% for OR. Despite significant differences in monitored unit utilization, pharmacy services, and respiratory therapy services by the OR group, the cost of EVAR is appreciably more expensive. Furthermore, increased DRG reimbursement, and decreased ICU use and LOS do not compensate for the cost of EVAR. The main cost of EVAR is the cost of the graft itself. Hospital profit margins are acceptable with both the EVAR and OR procedures at this time; however, with proposed reductions in reimbursement, the ability to cover the cost of this new technology may be threatened.

Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference.

The Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts in the field of vascular ultrasonography (US) to come to a consensus regarding Doppler US for assistance in the diagnosis of carotid artery stenosis. The panel's consensus statement is believed to represent a reasonable position on the basis of analysis of available literature and panelists' experience. Key elements of the statement include the following: (a) All internal carotid artery (ICA) examinations should be performed with gray-scale, color Doppler, and spectral Doppler US. (b) The degree of stenosis determined at gray-scale and Doppler US should be stratified into the categories of normal (no stenosis), <50% stenosis, 50%-69% stenosis, > or =70% stenosis to near occlusion, near occlusion, and total occlusion. (c) ICA peak systolic velocity (PSV) and presence of plaque on gray-scale and/or color Doppler images are primarily used in diagnosis and grading of ICA stenosis; two additional parameters, ICA-to-common carotid artery PSV ratio and ICA end-diastolic velocity may also be used when clinical or technical factors raise concern that ICA PSV may not be representative of the extent of disease. (d) ICA should be diagnosed as (i) normal when ICA PSV is less than 125 cm/sec and no plaque or intimal thickening is visible; (ii) <50% stenosis when ICA PSV is less than 125 cm/sec and plaque or intimal thickening is visible; (iii) 50%-69% stenosis when ICA PSV is 125-230 cm/sec and plaque is visible; (iv) > or =70% stenosis to near occlusion when ICA PSV is greater than 230 cm/sec and visible plaque and lumen narrowing are seen; (v) near occlusion when there is a markedly narrowed lumen at color Doppler US; and (vi) total occlusion when there is no detectable patent lumen at gray-scale US and no flow at spectral, power, and color Doppler US. (e) The final report should discuss velocity measurements and gray-scale and color Doppler findings. Study limitations should be noted when they exist. The conclusion should state an estimated degree of ICA stenosis as reflected in the above categories. The panel also considered various technical aspects of carotid US and methods for quality assessment and identified several important unanswered questions meriting future research.

Carotid artery stenosis: grayscale and Doppler ultrasound diagnosis--Society of Radiologists in Ultrasound consensus conference.

The Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts in the field of vascular ultrasonography (US) to come to a consensus regarding Doppler US for assistance in the diagnosis of carotid artery stenosis. The panel's consensus statement is believed to represent a reasonable position on the basis of analysis of available literature and panelists' experience. Key elements of the statement include the following: First, all internal carotid artery (ICA) examinations should be performed with grayscale, color Doppler, and spectral Doppler US. Second, the degree of stenosis determined at grayscale and Doppler US should be stratified into the categories of normal (no stenosis), less than 50% stenosis, 50 to 69% stenosis, > or =70% stenosis to near occlusion, near occlusion, and total occlusion. Third, ICA peak systolic velocity (PSV) and the presence of plaque on grayscale and/or color Doppler images are primarily used in the diagnosis and grading of ICA stenosis. Two additional parameters (the ICA-to-common carotid artery PSV ratio and ICA end diastolic velocity) may also be used when clinical or technical factors raise concern that ICA PSV may not be representative of the extent of disease. Fourth, ICA should be diagnosed as normal when ICA PSV is less than 125 cm/second and no plaque or intimal thickening is visible, less than 50% stenosis when ICA PSV is less than 125 cm/second and plaque or intimal thickening is visible, 50 to 69% stenosis when ICA PSV is 125 to 230 cm/second and plaque is visible, > or =70% stenosis to near occlusion when ICA PSV is more than 230 cm/second and visible plaque and lumen narrowing are seen, near occlusion when there is a markedly narrowed lumen on color Doppler US, and total occlusion when there is no detectable patent lumen on grayscale US and no flow on spectral, power, and color Doppler US. Fifth, the final report should discuss velocity measurements and grayscale and color Doppler findings. Study limitations should be noted when they exist. The conclusion should state an estimated degree of ICA stenosis as reflected in these categories. The panel also considered various technical aspects of carotid US and methods for quality assessment, and identified several important unanswered questions meriting future research.