Todd D. Reil

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.

Infrapopliteal-Lower Extremity Revascularization with Prosthetic Conduit: A 20-Year Experience

The use of prosthetic conduits for lower extremity revascularization in the infrapopliteal location remains controversial. The objective of this report is to describe the immediate and long-term results in a series collected over two decades. Of the approximately 1,500 lower extremity revascularizations performed between 1978 and 1998, 81 infrapopliteal bypass cases using polytetrafluoroethylene (PTFE) as conduit in 77 patients were identified. Autogenous conduit was unavailable (86%) due to prior surgery: coronary artery bypass graft (25%), femoro-popliteal bypass (60%), or femoro-distal bypass (23%). All cases were done for critical ischemia using PTFE (6 mm, 95%; ring reinforced, 54%) under general (75%) or regional (25%) anesthesia. The distal anastomosis was to the anterior tibial artery (43%), posterior tibial artery (28%), tibioperoneal trunk (16%), or peroneal artery (12%), and vein patch was used in 25% of cases. Postoperative features included acute graft thrombosis in 11 cases (14%), all done under general anesthesia, perioperative death in 3 (4%), and a mean in-hospital stay of 17 days. Long-term follow-up has ranged from 1 to 144 months (mean, 22 months). At 36 months, primary patency was 20%, secondary patency 42%, and limb salvage 55% calculated by the Kaplan-Meier method. Univariate analyses revealed regional anesthesia was associated with prolonged primary patency (35% vs 15%, p = 0.026) while the use of ringreinforced PTFE conduit was associated with prolonged limb salvage (65% vs 40%, p = 0.042). All other variables including gender, smoking, diabetes mellitus, renal failure, decade of operation, use of vein patch or postoperative warfarin were not significantly associated with either prolonged patency or limb salvage. Despite poor primary patency, distal prosthetic bypass can lead to long-term limb salvage. These data suggest distal anastomotic vein patches and postoperative anticoagulation may not be beneficial adjuncts. However, the use of regional anesthesia may decrease the incidence of perioperative thrombosis and the use of ring reinforced conduit may prolong limb salvage.

Combined Carotid Endarterectomy and Coronary Bypass: A Decade Experience at UCLA:

PURPOSE The purpose of this review was to determine outcomes for combined carotid endarterectomy (CEA) and coronary revascularization (CABG) in patients with asymptomatic carotid stenosis. METHODS We reviewed the medical records of consecutive combined procedures (CEA and CABG), performed at UCLA Medical Center from October, 1989 to January, 1999. FINDINGS There were 43 patients, 27 men and 16 women, with a mean age of 71 yr (range 51-87). Thirty-four patients 79% (34/43) had asymptomatic carotid stenosis. Stroke occurred in three patients (3/43 = 6.9%). Stroke ipsilateral to the CEA occurred in two patients: one asymptomatic (1/34 = 2.9%) and one symptomatic (1/9 = 11.1%). CONCLUSIONS The majority of patients undergoing combined CEA/CABG have asymptomatic carotid stenosis identified in preparation for elective CABG. The asymptomatic carotid subset stroke rate of 2.9% resulting from a combined CEA/CABG is higher than our reported rate for CEA performed alone. In patients with asymptomatic carotid stenosis, the combined procedure should be selectively performed.

Extracranial Internal Carotid Artery Mycotic Aneurysm: Case Report and Review

Mycotic aneurysms of the internal carotid artery (ICA) are rare and often difficult to diagnose. They can have nonspecific signs and symptoms, an unclear etiology, and can lead to severe morbidity and mortality if left untreated. We present a case of a 47-year-old woman with an apparent mycotic aneurysm of the extracranial ICA associated with Klebsiella pneumonia. We discuss the various clinical findings and radiographic imaging that lead to this unusual diagnosis and the details of our surgical treatment, which included excision of the mycotic aneurysm and reconstruction with a greater saphenous vein interposition graft. We also review the literature on mycotic aneurysms of the ICA, including the radiologic modalities available to diagnose this condition, epidemiology, pathophysiology, and treatment options.

Endovascular exclusion of superior mesenteric artery pseudoaneurysms: an alternative to open laparotomy in high-risk patients.

Superior mesenteric artery (SMA) aneurysms are rare. However, patients are frequently symptomatic on presentation and require urgent repair. SMA aneurysms have the potential for severe complications, including thrombosis or rupture, resulting in acute mesenteric ischemia and death. In patients with adhesions secondary to prior abdominal surgery, traditional open exposure of the aneurysm neck via dissection at the base of the transverse colon mesentery may be technically difficult. Endovascular exclusion of visceral artery aneurysms using covered stent grafts presents a reasonable alternative to the morbidity associated with laparotomy. We report an interesting case of a patient with a large SMA aneurysm and multiple prior laparotomies treated percutaneously with a combined expanded polytetrafluoroethylene/nitinol self-expanding stent-graft allowing maintenance of end-organ perfusion and bowel viability.

Diagnosis of vulnerable atherosclerotic plaques by time-resolved fluorescence spectroscopy and ultrasound imaging.

In this study, time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and ultrasonography were applied to detect vulnerable (high-risk) atherosclerotic plaque. A total of 813 TR-LIFS measurements were taken from carotid plaques of 65 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified by histopathology as thin, fibrotic, calcified, low-inflamed, inflamed and necrotic lesions. Spectral and time-resolved parameters (normalized intensity values and Laguerre expansion coefficients) were extracted from the TR-LIFS data. Feature selection for classification was performed by either analysis of variance (ANOVA) or principal component analysis (PCA). A stepwise linear discriminant analysis algorithm was developed for detecting inflamed and necrotic lesion, representing the most vulnerable plaques. These vulnerable plaques were detected with high sensitivity (>80%) and specificity (>90%). Ultrasound (US) imaging was obtained in 4 carotid plaques in addition to TR-LIFS examination. Preliminary results indicate that US provides important structural information of the plaques that could be combined with the compositional information obtained by TR-LIFS, to obtain a more accurate diagnosis of vulnerable atherosclerotic plaque

Application of the Laguerre Deconvolution Method for Time-Resolved Fluorescence Spectroscopy to the Characterization of Atherosclerotic Plaques

This study investigates the ability of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) to detect inflammation in atherosclerotic lesion, a key feature of plaque vulnerability. A total of 348 TR-LIFS measurements were taken from carotid plaques of 30 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as early, fibrotic/calcified or inflamed lesions. A stepwise linear discriminant analysis algorithm was developed using spectral and TR features (normalized intensity values and Laguerre expansion coefficients at discrete emission wavelengths, respectively). Features from only three emission wavelengths (390, 450 and 500 nm) were used in the classifier. The inflamed lesions were discriminated with sensitivity > 80% and specificity >90 %, when the Laguerre expansion coefficients were included in the feature space. These results indicate that TR-LIFS information derived from the Laguerre expansion coefficients at few selected emission wavelengths can discriminate inflammation in atherosclerotic plaques. We believe that TR-LIFS derived Laguerre expansion coefficients can provide a valuable additional dimension for the detection of vulnerable plaques

Novel methods of time-resolved fluorescence data analysis for in-vivo tissue characterization: application to atherosclerosis

This study investigates the ability of new analytical methods of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data to characterize tissue in-vivo, such as the composition of atherosclerotic vulnerable plaques. A total of 73 TR-LIFS measurements were taken in-vivo from the aorta of 8 rabbits, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as normal aorta, thin or thick lesions, and lesions rich in either collagen or macrophages/foam-cells. Different linear and nonlinear classification algorithms (linear discriminant analysis, stepwise linear discriminant analysis, principal component analysis, and feedforward neural networks) were developed using spectral and TR features (ratios of intensity values and Laguerre expansion coefficients, respectively). Normal intima and thin lesions were discriminated from thick lesions (sensitivity >90%, specificity 100%) using only spectral features. However, both spectral and time-resolved features were necessary to discriminate thick lesions rich in collagen from thick lesions rich in foam cells (sensitivity >85%, specificity >93%), and thin lesions rich in foam cells from normal aorta and thin lesions rich in collagen (sensitivity >85%, specificity >94%). Based on these findings, we believe that TR-LIFS information derived from the Laguerre expansion coefficients can provide a valuable additional dimension for in-vivo tissue characterization.

Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia--a case report.

Heparin use, both prophylactically and therapeutically, is prevalent among hospitalized patients. Patients on heparin may develop a thrombocytopenia that is self-limited. Fewer patients develop a heparin-induced thrombocytopenia that can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. The authors present a case report of heparininduced thrombocytopenia in a patient who underwent aortic arch and aortic valve replacement that resulted in bilateral above-knee amputations. The patient developed limb ischemia related to heparin-associated thrombosis, but had a delay in antibody seroconversion. Early and accurate diagnosis of heparin-induced thrombocytopenia requires a high clinical suspicion and may be present despite the absence of serum antibodies.