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Ismail MA, Mounir O, Sedky A, Algahlan HA, Abda EA, Radwan AR, Abozaid HS. Exists a role for serum irisin in Egyptian Behcet's patients with subclinical atherosclerosis? Clin Rheumatol 2023; 42:179-186. [PMID: 36112245 PMCID: PMC9823020 DOI: 10.1007/s10067-022-06368-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 09/01/2022] [Accepted: 09/02/2022] [Indexed: 01/11/2023]
Abstract
OBJECTIVES To examine the serum irisin level in a group of Behcet's disease patients, its association with illness parameters, and its utility in diagnosing subclinical atherosclerosis. METHODS This randomized case-control study included 50 patients and 50 age- and sex-matched controls. Carotid Doppler ultrasound for the measurement of the carotid artery intima-media thickness (CIMT) and ankle-brachial pressure index (ABPI) were performed. A clinical evaluation, lipogram, and serum irisin were also performed. RESULTS Between the patients and the control group, there was a significant difference in CIMT, S. irisin level, and ankle-brachial pressure index; however, gender and BMI did not significantly affect CIMT, ABPI, or S. irisin level. CIMT demonstrated a substantial negative correlation with both S. irisin and ABPI (r = - 0.62, P 0.0001). With a sensitivity of up to 94.30% and a specificity of 93.30%, the ROC analysis revealed that a decrease in S. irisin level in Behcet's patients was indicative of subclinical atherosclerosis. The drop in the ABPI level demonstrated a sensitivity of up to 94.30% and a specificity of 100%. CONCLUSION Subclinical atherosclerosis is prevalent among Egyptian Behcet's patients, and S. irisin can be employed as a biomarker for diagnosing subclinical atherosclerosis in Behcet's illness. Key Points • Serum irisin has been studied in numerous autoimmune disorders as a marker for subclinical atherosclerosis, although its importance in Behcet's disease remains unclear (BD). • We examined the change in serum irisin levels in Behcet's disease patients and healthy controls. In addition, its association with carotid artery intima-media thickness (CIMT) and ankle-brachial pressure index was investigated (ABPI). • Changes in serum irisin levels are significant in BD, and a decrease in irisin level indicates subclinical atherosclerosis.
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Affiliation(s)
- Mohamed A Ismail
- Department of Rheumatology and Rehabilitation, Sohag University Hospital, 82524, Sohag, Egypt
| | - Ola Mounir
- Department of Rheumatology and Rehabilitation, Sohag University Hospital, 82524, Sohag, Egypt
| | - Ahmed Sedky
- Department of Clinical Pathology, Sohag University, Sohag, Egypt
| | | | - Esam A Abda
- Department of Rheumatology and Rehabilitation, Assuit University, Asyut, Egypt
| | - Ahmed R Radwan
- Department of Rheumatology and Rehabilitation, Sohag University Hospital, 82524, Sohag, Egypt
| | - Hanan Sayed Abozaid
- Department of Rheumatology and Rehabilitation, Sohag University Hospital, 82524, Sohag, Egypt.
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Huang C, Huang W, Zhang L, Zhang C, Zhou C, Wei W, Li Y, Zhou Q, Chen W, Tang Y. Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy. Pharmaceutics 2022; 14:1083. [PMID: 35631669 PMCID: PMC9146689 DOI: 10.3390/pharmaceutics14051083] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/09/2022] [Accepted: 05/16/2022] [Indexed: 11/26/2022] Open
Abstract
Atherosclerosis is the leading cause of global morbidity and mortality. Its therapy requires research in several areas, such as diagnosis of early arteriosclerosis, improvement of the pharmacokinetics and bioavailability of rapamycin as its therapeutic agents. Here, we used the targeting peptide VHPKQHR (VHP) (or fluorescent reagent) to modify the phospholipid molecules to target vascular cell adhesion molecule-1 (VCAM-1) and loaded ultrasmall paramagnetic iron oxide (USPIO/Fe3O4) plus rapamycin (Rap) to Rap/Fe3O4@VHP-Lipo (VHPKQHR-modified magnetic liposomes coated with Rap). This nanoparticle can be used for both the diagnosis and therapy of early atherosclerosis. We designed both an ex vivo system with mouse aortic endothelial cells (MAECs) and an in vivo system with ApoE knockout mice to test the labeling and delivering potential of Rap/Fe3O4@VHP-Lipo with fluorescent microscopy, flow cytometry and MRI. Our results of MRI imaging and fluorescence imaging showed that the T2 relaxation time of the Rap/Fe3O4@VHP-Lipo group was reduced by 2.7 times and 1.5 times, and the fluorescence intensity increased by 3.4 times and 2.5 times, respectively, compared with the normal saline group and the control liposome treatment group. It showed that Rap/Fe3O4@VHP-Lipo realized the diagnosis of early AS. Additionally, our results showed that, compared with the normal saline and control liposomes treatment group, the aortic fluorescence intensity of the Rap/Fe3O4@VHP-Lipo treatment group was significantly weaker, and the T2 relaxation time was prolonged by 8.9 times and 2.0 times, indicating that the targeted diagnostic agent detected the least plaques in the Rap/Fe3O4@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/Fe3O4@VHP-Lipo serves as a great label for both MRI and fluorescence bimodal imaging of atherosclerosis. It also has therapeutic effects for the early treatment of atherosclerosis, and it has great potential for early diagnosis and can achieve the same level of therapy with a lower dose of Rap.
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Affiliation(s)
- Chen Huang
- Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China;
| | - Wentao Huang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Lifen Zhang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Chunyu Zhang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Chengqian Zhou
- Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA;
| | - Wei Wei
- Institution of Guang Dong Cord Blood Bank, Guangzhou 510700, China; (W.W.); (Y.L.)
| | - Yongsheng Li
- Institution of Guang Dong Cord Blood Bank, Guangzhou 510700, China; (W.W.); (Y.L.)
| | - Quan Zhou
- Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
| | - Wenli Chen
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Yukuan Tang
- Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China;
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Gimnich OA, Zil-E-Ali A, Brunner G. Imaging Approaches to the Diagnosis of Vascular Diseases. Curr Atheroscler Rep 2022; 24:85-96. [PMID: 35080717 PMCID: PMC11619728 DOI: 10.1007/s11883-022-00988-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Vascular imaging is a complex field including numerous modalities and imaging markers. This review is focused on important and recent findings in atherosclerotic carotid artery plaque imaging with an emphasis on developments in magnetic resonance imaging (MRI) and computed tomography (CT). RECENT FINDINGS Recent evidence shows that carotid plaque characteristics and not only established measures of carotid plaque burden and stenosis are associated independently with cardiovascular outcomes. On carotid MRI, the presence of a lipid-rich necrotic core (LRNC) has been associated with incident cardiovascular disease (CVD) events independent of wall thickness, a traditional measure of plaque burden. On carotid MRI, intraplaque hemorrhage (IPH) presence has been identified as an independent predictor of stroke. The presence of a fissured carotid fibrous cap has been associated with contrast enhancement on CT angiography imaging. Carotid artery plaque characteristics have been associated with incident CVD events, and advanced plaque imaging techniques may gain additional prominence in the clinical treatment decision process.
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Affiliation(s)
- Olga A Gimnich
- Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Ahsan Zil-E-Ali
- Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Gerd Brunner
- Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, PA, USA.
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Pulsipher KW, Hammer DA, Lee D, Sehgal CM. Engineering Theranostic Microbubbles Using Microfluidics for Ultrasound Imaging and Therapy: A Review. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2441-2460. [PMID: 30241729 PMCID: PMC6643280 DOI: 10.1016/j.ultrasmedbio.2018.07.026] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/05/2018] [Accepted: 07/27/2018] [Indexed: 05/05/2023]
Abstract
Microbubbles interact with ultrasound in various ways to enable their applications in ultrasound imaging and diagnosis. To generate high contrast and maximize therapeutic efficacy, microbubbles of high uniformity are required. Microfluidic technology, which enables precise control of small volumes of fluid at the sub-millimeter scale, has provided a versatile platform on which to produce highly uniform microbubbles for potential applications in ultrasound imaging and diagnosis. Here, we describe fundamental microfluidic principles and the most common types of microfluidic devices used to produce sub-10 μm microbubbles, appropriate for biomedical ultrasound. Bubbles can be engineered for specific applications by tailoring the bubble size, inner gas and shell composition and by functionalizing for additional imaging modalities, therapeutics or targeting ligands. To translate the laboratory-scale discoveries to widespread clinical use of these microfluidic-based microbubbles, increased bubble production is needed. We present various strategies recently developed to improve scale-up. We conclude this review by describing some outstanding problems in the field and presenting areas for future use of microfluidics in ultrasound.
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Affiliation(s)
- Katherine W Pulsipher
- Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Daniel A Hammer
- Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Daeyeon Lee
- Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Chandra M Sehgal
- Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA.
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Prévot G, Kauss T, Lorenzato C, Gaubert A, Larivière M, Baillet J, Laroche-Traineau J, Jacobin-Valat MJ, Adumeau L, Mornet S, Barthélémy P, Duonor-Cérutti M, Clofent-Sanchez G, Crauste-Manciet S. Iron oxide core oil-in-water nanoemulsion as tracer for atherosclerosis MPI and MRI imaging. Int J Pharm 2017; 532:669-676. [PMID: 28899764 DOI: 10.1016/j.ijpharm.2017.09.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 09/04/2017] [Accepted: 09/05/2017] [Indexed: 12/20/2022]
Abstract
PURPOSE For early atherosclerosis imaging, magnetic oil-in-water nanoemulsion (NE) decorated with atheroma specific monoclonal antibody was designed for Magnetic Particle Imaging (MPI) and Magnetic Resonance Imaging (MRI). MPI is an emerging technique based on direct mapping of superparamagnetic nanoparticles which may advantageously complement MRI. METHODS NE oily droplets were loaded with superparamagnetic iron oxide nanoparticles of 7, 11 and 18nm and biofunctionalized with atheroma specific scFv-Fc TEG4-2C antibody. RESULTS Inclusion of nanoparticles inside NE did not change the hydrodynamic diameter of the oil droplets, close to 180nm, nor the polydispersity. The droplets were negatively charged (ζ=-30mV). In vitro MPI signal was assessed by Magnetic Particle Spectroscopy (MPS). NE displayed MRI and MPS signals confirming its potential as new contrast agent. NE MPS signal increase with NPs size close to the gold standard (Resovist). In MRI, NE displayed R2* transversal relaxivity of 45.45, 96.04 and 218.81mM-1s-1 for 7, 11 and 18nm respectively. NE selectively bind atheroma plaque both in vitro and ex vivo in animal models of atherosclerosis. CONCLUSION Magnetic NE showed reasonable MRI/MPS signals and a significant labelling of the atheroma plaque. These preliminary results support that NE platform could selectively image atherosclerosis.
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Affiliation(s)
- Geoffrey Prévot
- Univ. Bordeaux, INSERM, U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, F-33000, Bordeaux, France
| | - Tina Kauss
- Univ. Bordeaux, INSERM, U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, F-33000, Bordeaux, France
| | - Cyril Lorenzato
- Univ. Bordeaux, CNRS UMR 5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, F-33000, Bordeaux, France
| | - Alexandra Gaubert
- Univ. Bordeaux, INSERM, U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, F-33000, Bordeaux, France
| | - Mélusine Larivière
- Univ. Bordeaux, CNRS UMR 5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, F-33000, Bordeaux, France
| | - Julie Baillet
- Univ. Bordeaux, INSERM, U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, F-33000, Bordeaux, France
| | - Jeanny Laroche-Traineau
- Univ. Bordeaux, CNRS UMR 5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, F-33000, Bordeaux, France
| | - Marie Josée Jacobin-Valat
- Univ. Bordeaux, CNRS UMR 5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, F-33000, Bordeaux, France
| | - Laurent Adumeau
- CNRS, Univ. Bordeaux, ICMCB, UPR 9048, F-33600, Pessac, France
| | - Stéphane Mornet
- CNRS, Univ. Bordeaux, ICMCB, UPR 9048, F-33600, Pessac, France
| | - Philippe Barthélémy
- Univ. Bordeaux, INSERM, U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, F-33000, Bordeaux, France
| | | | - Gisèle Clofent-Sanchez
- Univ. Bordeaux, CNRS UMR 5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, F-33000, Bordeaux, France
| | - Sylvie Crauste-Manciet
- Univ. Bordeaux, INSERM, U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, F-33000, Bordeaux, France.
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Suzuki T, Nazarian S, Jerosch-Herold M, Chugh SS. Imaging for assessment of sudden death risk: current role and future prospects. Europace 2016; 18:1491-1500. [PMID: 27098112 DOI: 10.1093/europace/euv456] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2015] [Accepted: 12/28/2015] [Indexed: 12/18/2022] Open
Abstract
Sudden cardiac death (SCD) remains a major public health problem and there is an urgent need to maximize the impact of primary prevention using the implantable defibrillator. While implantable defibrillators are of utility for prevention of SCD, current methods of selecting candidates have significant shortcomings. Major advancements have occurred in the field of cardiac imaging, with significant potential to identify novel cardiac substrates for improved prediction. While assessment of the left ventricular ejection fraction remains the current major predictor, it is likely that several novel imaging markers will be incorporated into future risk stratification approaches. The goal of this review is to discuss the current status and future potential of cardiac imaging modalities to enhance risk stratification for SCD.
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Affiliation(s)
- Takeki Suzuki
- Division of Cardiology, Department of Medicine, University of Mississippi, Jackson, MS, USA
| | - Saman Nazarian
- Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | | | - Sumeet S Chugh
- The Heart Institute, Advanced Health Sciences Pavilion Suite A3100, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, Los Angeles, CA 90048, USA
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Nagao R, Ishii K, Matsui D, Awazu K. Quantitative Evaluation of Lipid Volume Fraction in Atherosclerotic Plaque Phantoms by Near-infrared Multispectral Imaging at Wavelengths around 1200 nm. ADVANCED BIOMEDICAL ENGINEERING 2015. [DOI: 10.14326/abe.4.158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Ryo Nagao
- Graduate School of Engineering, Osaka University
| | | | | | - Kunio Awazu
- Graduate School of Engineering, Osaka University
- Graduate School of Frontier Biosciences, Osaka University
- Global Center for Medical Engineering and Informatics, Osaka University
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Sato A. Coronary plaque imaging by coronary computed tomography angiography. World J Radiol 2014; 6:148-159. [PMID: 24876919 PMCID: PMC4037541 DOI: 10.4329/wjr.v6.i5.148] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 02/09/2014] [Accepted: 04/17/2014] [Indexed: 02/06/2023] Open
Abstract
Coronary computed tomography angiography (CTA) has become the useful noninvasive imaging modality alternative to the invasive coronary angiography for detecting coronary artery stenoses in patients with suspected coronary artery disease (CAD). With the development of technical aspects of coronary CTA, clinical practice and research are increasingly shifting toward defining the clinical implication of plaque morphology and patients outcomes by coronary CTA. In this review we discuss the coronary plaque morphology estimated by CTA beyond coronary angiography including the comparison to the currently available other imaging modalities used to examine morphological characteristics of the atherosclerotic plaque. Furthermore, this review underlies the value of a combined assessment of coronary anatomy and myocardial perfusion in patients with CAD, and adds to an increasing body of evidence suggesting an added diagnostic value when combining both modalities. We hope that an integrated, multi-modality imaging approach will become the gold standard for noninvasive evaluation of coronary plaque morphology and outcome data in clinical practice.
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Caglar IM, Demir B, Caglar FNT, Vural A, Ugurlucan M, Ciftci S, Ungan I, Gedikbasi A, Dasli T, Karakaya O. Contrast Layering. Angiology 2014; 66:136-42. [DOI: 10.1177/0003319714520955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Patients with angiographically normal coronary arteries sometimes exhibit delayed clearance of contrast medium. This contrast layering (CL) was tested with intravascular ultrasound (IVUS) and markers of endothelial dysfunction and oxidative stress. The study group (n = 26) consisted of patients with CL and the control group (n = 32) comprised patients with normal coronary arteries despite angina symptoms. The CL was observed in 36 coronary arteries of 26 patients in the study group. Total antioxidant status and nitric oxide levels were significantly lower; total oxidant status, malondialdehyde plasma levels, and oxidative stress index were significantly higher in patients with CL than in controls. The IVUS studies revealed that atherosclerotic plaque burden, fibrous tissue, dense calcific tissue, and necrotic core ratios were significantly higher in the coronary segments with CL compared with adjacent normal segments. These results support the concept of CL as a new angiographic appearance of early atherosclerosis.
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Affiliation(s)
- Ilker Murat Caglar
- Department of Cardiology, Bakirkoy Dr Sadi Konuk Research and Education Hospital, Istanbul, Turkey
| | - Bulent Demir
- Department of Cardiology, Bakirkoy Dr Sadi Konuk Research and Education Hospital, Istanbul, Turkey
| | | | - Alper Vural
- Department of Cardiology, Bakirkoy Dr Sadi Konuk Research and Education Hospital, Istanbul, Turkey
| | - Murat Ugurlucan
- Department of Cardiovascular Surgery, Istanbul University Faculty of Medicine, Istanbul, Turkey
| | - Serkan Ciftci
- Department of Cardiology, Bakirkoy Dr Sadi Konuk Research and Education Hospital, Istanbul, Turkey
| | - Ismail Ungan
- Department of Cardiology, Bakirkoy Dr Sadi Konuk Research and Education Hospital, Istanbul, Turkey
| | - Asuman Gedikbasi
- Department of Clinical Biochemistry, Bakirkoy Dr. Sadi Konuk Research and Education Hospital, Istanbul, Turkey
| | - Tolga Dasli
- Department of Cardiology, Kocaeli Derince Research and Education Hospital, Kocaeli, Turkey
| | - Osman Karakaya
- Department of Cardiology, Bakirkoy Dr Sadi Konuk Research and Education Hospital, Istanbul, Turkey
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Kim KH, Kim WH, Park HW, Song IG, Yang DJ, Seo YH, Yuk HB, Park YH, Kwon TG, Rihal CS, Lerman A, Lee MS, Bae JH. Impact of plaque composition on long-term clinical outcomes in patients with coronary artery occlusive disease. Korean Circ J 2013; 43:377-83. [PMID: 23882286 PMCID: PMC3717420 DOI: 10.4070/kcj.2013.43.6.377] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Revised: 05/20/2013] [Accepted: 05/31/2013] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND AND OBJECTIVES It is unclear which plaque component is related with long-term clinical outcomes in patients with coronary artery occlusive disease (CAOD). We assessed the relationship between plaque compositions and long-term clinical outcomes in those patients. SUBJECTS AND METHODS The study subjects consisted of 339 consecutive patients (mean 61.7±12.2 years old, 239 males) who underwent coronary angiogram and a virtual histology-intravascular ultrasound examination. Major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, non-fatal myocardial infarction, cerebrovascular events, and target vessel revascularization were evaluated during a mean 28-month follow-up period. RESULTS Patients with high fibrofatty volume (FFV, >8.90 mm(3), n=169) had a higher incidence of MACCE (25.4% vs. 14.7%, p=0.015), male sex (75.7% vs. 65.3%, p=0.043), acute coronary syndrome (53.3% vs. 35.9%, p=0.002), multivessel disease (62.7% vs. 41.8%, p<0.001) and post-stent slow flow (10.7% vs. 2.4%, p=0.002) than those with low FFV (FFV≤8.90 mm(3), n=170). Other plaque composition factors such as fibrous area/volume, dense calcified area/volume, and necrotic core area/volume did not show any impact on MACCE. Cardiogenic shock {hazard ratio (HR)=8.44; 95% confidence interval (CI)=3.00-23.79; p<0.001} and FFV (HR=1.85; 95% CI=1.12-3.07; p=0.016) were the independent predictors of MACCE by Cox regression analysis. Thin-cap fibroatheroma, necrotic core area, and necrotic core volume were not associated with MACCE. CONCLUSION FFV of a culprit lesion was associated with unfavorable long-term clinical outcomes in patients with CAOD.
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Affiliation(s)
- Ki Hong Kim
- Division of Cardiology, Konyang University Hospital, Daejeon, Korea
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Maurovich-Horvat P, Schlett CL, Alkadhi H, Nakano M, Stolzmann P, Vorpahl M, Scheffel H, Tanaka A, Warger WC, Maehara A, Ma S, Kriegel MF, Kaple RK, Seifarth H, Bamberg F, Mintz GS, Tearney GJ, Virmani R, Hoffmann U. Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts. Radiology 2012; 265:393-401. [PMID: 23012461 DOI: 10.1148/radiol.12111891] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. MATERIALS AND METHODS All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. RESULTS Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P<.0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, P<.0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P<.0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ=0.87 and 0.85, respectively) and was good for intravascular US (κ=0.66). CONCLUSION Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are reasonably associated with plaque composition and lesion grading according to histopathologic findings, while OFDI was strongly associated. These data may help to develop initial concepts of sequential imaging strategies to identify patients with advanced coronary plaques.
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Affiliation(s)
- Pál Maurovich-Horvat
- Cardiac MR PET CT Program of the Department of Radiology, Cardiology Division, and Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 165 Cambridge St, Suite 400, Boston, MA 02114, USA
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Zynda TK, Thompson CD, Hoang KC, Seto AH, Glovaci D, Wong ND, Patel PM, Kern MJ. Disparity between angiographic coronary lesion complexity and lipid core plaques assessed by near-infrared spectroscopy. Catheter Cardiovasc Interv 2012; 81:529-37. [PMID: 22532512 DOI: 10.1002/ccd.24470] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 03/22/2012] [Accepted: 04/21/2012] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The purpose of this study was to determine if there was a relationship between angiographic lesion complexity and the extent of lipid core plaque (LCP) identified by catheter-based near-infrared spectroscopy (NIRS). BACKGROUND The angiographic complexity of coronary artery disease (CAD) is used to predict outcomes in patients undergoing percutaneous coronary intervention (PCI). The SYNTAX score, an angiographic tool quantifying the complexity of CAD, is associated with PCI outcomes. Recently, a novel catheter-based imaging technique using NIRS can identify LCP, which also is associated with PCI periprocedural myocardial infarction (MI). However, it is unknown whether these events are related to distinct adverse event prone pathobiology, such as a LCP within a complex angiographic lesion. Thus, we hypothesized that LCP identified by NIRS would be associated with high SYNTAX score. METHODS Seventy-eight patients who underwent coronary angiography and target-vessel NIRS were selected from the Chemometric Observations of Lipid Core Containing Plaques of Interest in Native Coronary Arteries Registry, an industry sponsored registry to collate clinical findings in all patients undergoing NIRS evaluation. A lipid core burden index (LCBI) was obtained from the scan of the proximal 50 mm of the target vessel. Three vessel SYNTAX (total, tSYN) and target single vessel (only NIRS-interrogated vessel) SYNTAX (1vSYN) scores were calculated and compared to LCBI. High LCBI was defined as (>110) and was compared to tertile scores for 1vSYN score (low 0-5, intermediate 6-10, high ≥11) and previously established tertiles for tSYN score (low 0-22, intermediate 23-32, high ≥33). RESULTS Patients had mean age of 63 years with prevalence of females (10%), diabetes mellitus (28%), hypertension (88%), and smoking history (72%); 1vSYN and tSYN scores correlated poorly with LCBI [(r(2) = 0.25; P = 0.02; n = 78) and (r(2) = 0.24; P = 0.04; n = 78), respectively]. Mean LCBI did not differ significantly across all tertiles of 1vSYN or tSYN scores. CONCLUSIONS Angiographic SYNTAX score only weakly correlated with LCBI. It is of interest as well that high LCBI was also present in cases of low SYNTAX scores. The disparity between the degree of angiographic complexity and the amount of LCP supports postulated mechanisms of the adverse event propensity even in patients who demonstrate low angiographic complexity. Future studies are necessary to address the clinical significance of high LCBI in patients with low-to-intermediate angiographic complexity and their potential for PCI-related complications.
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Affiliation(s)
- Todd K Zynda
- Department of Medicine, University of California, Orange, CA, USA
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Fleg JL, Stone GW, Fayad ZA, Granada JF, Hatsukami TS, Kolodgie FD, Ohayon J, Pettigrew R, Sabatine MS, Tearney G, Waxman S, Domanski MJ, Srinivas PR, Narula J. Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions. JACC Cardiovasc Imaging 2012; 5:941-55. [PMID: 22974808 PMCID: PMC3646061 DOI: 10.1016/j.jcmg.2012.07.007] [Citation(s) in RCA: 164] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2012] [Revised: 07/18/2012] [Accepted: 07/19/2012] [Indexed: 12/27/2022]
Abstract
The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis.
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Affiliation(s)
- Jerome L. Fleg
- National Heart, Lung and Blood Institute, Bethesda, Maryland
| | - Gregg W. Stone
- Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York
| | | | - Juan F. Granada
- Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York
| | | | | | - Jacques Ohayon
- National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, Maryland
| | - Roderic Pettigrew
- National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, Maryland
| | - Marc S. Sabatine
- Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | - Guillermo Tearney
- Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | | | | | | | - Jagat Narula
- Mount Sinai School of Medicine, New York, New York
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Soloperto G, Casciaro S. Progress in atherosclerotic plaque imaging. World J Radiol 2012; 4:353-71. [PMID: 22937215 PMCID: PMC3430733 DOI: 10.4329/wjr.v4.i8.353] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Revised: 05/14/2012] [Accepted: 05/21/2012] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods.
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15
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Razansky D, Harlaar NJ, Hillebrands JL, Taruttis A, Herzog E, Zeebregts CJ, van Dam GM, Ntziachristos V. Multispectral optoacoustic tomography of matrix metalloproteinase activity in vulnerable human carotid plaques. Mol Imaging Biol 2012; 14:277-85. [PMID: 21720908 PMCID: PMC3346936 DOI: 10.1007/s11307-011-0502-6] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
AIMS Elevated expression of cathepsins, integrins and matrix metalloproteinases (MMPs) is typically associated with atherosclerotic plaque instability. While fluorescent tagging of such molecules has been amply demonstrated, no imaging method was so far shown capable of resolving these inflammation-associated tags with high fidelity and resolution beyond microscopic depths. This study is aimed at demonstrating a new method with high potential for noninvasive clinical cardiovascular diagnostics of vulnerable plaques using high-resolution deep-tissue multispectral optoacoustic tomography (MSOT) technology. METHODS AND RESULTS MMP-sensitive activatable fluorescent probe (MMPSense™ 680) was applied to human carotid plaques from symptomatic patients. Atherosclerotic activity was detected by tuning MSOT wavelengths to activation-dependent absorption changes of the molecules, structurally modified in the presence of enzymes. MSOT analysis simultaneously provided morphology along with heterogeneous MMP activity with better than 200 micron resolution throughout the intact plaque tissue. The results corresponded well with epi-fluorescence images made from thin cryosections. Elevated MMP activity was further confirmed by in situ zymography, accompanied by increased macrophage influx. CONCLUSIONS We demonstrated, for the first time to our knowledge, the ability of MSOT to provide volumetric images of activatable molecular probe distribution deep within optically diffuse tissues. High-resolution mapping of MMP activity was achieved deep in the vulnerable plaque of intact human carotid specimens. This performance directly relates to pre-clinical screening applications in animal models and to clinical decision potential as it might eventually allow for highly specific visualization and staging of plaque vulnerability thus impacting therapeutic clinical decision making.
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Affiliation(s)
- Daniel Razansky
- Institute for Biological and Medical Imaging, Technische Universität München and Helmholtz Zentrum München, Munich, Germany
| | - Niels J. Harlaar
- Institute for Biological and Medical Imaging, Technische Universität München and Helmholtz Zentrum München, Munich, Germany
- Department of Surgery and Bio-optical Imaging Center Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jan Luuk Hillebrands
- Department of Pathology and Medical Biology, Pathology Division, University Medical Center Groningen, Groningen, The Netherlands
| | - Adrian Taruttis
- Institute for Biological and Medical Imaging, Technische Universität München and Helmholtz Zentrum München, Munich, Germany
| | - Eva Herzog
- Institute for Biological and Medical Imaging, Technische Universität München and Helmholtz Zentrum München, Munich, Germany
| | - Clark J. Zeebregts
- Department of Surgery and Bio-optical Imaging Center Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Gooitzen M. van Dam
- Department of Surgery and Bio-optical Imaging Center Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Vasilis Ntziachristos
- Institute for Biological and Medical Imaging, Technische Universität München and Helmholtz Zentrum München, Munich, Germany
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Inhibition of sPLA2 and Endothelial Function: A Substudy of the SPIDER-PCI Trial. Can J Cardiol 2012; 28:215-21. [DOI: 10.1016/j.cjca.2011.11.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Revised: 11/08/2011] [Accepted: 11/08/2011] [Indexed: 01/06/2023] Open
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Longitudinal heterogeneity of coronary artery distensibility in plaques related to acute coronary syndrome. Clin Res Cardiol 2012; 101:545-51. [PMID: 22322568 DOI: 10.1007/s00392-012-0424-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2010] [Accepted: 01/31/2012] [Indexed: 10/14/2022]
Abstract
BACKGROUND How coronary distensibility contributes to stable or unstable clinical manifestations remains obscure. We postulated that the heterogeneous plaque distensibility is associated with unstable clinical presentations in patients with acute coronary syndrome (ACS). METHODS AND RESULTS Seventeen and 19 ACS-related and -unrelated lesions, respectively, were visualized using intravascular ultrasound imaging with simultaneous intracoronary pressure recording. Systolic and diastolic lumen cross-sectional areas were measured at the lesion site and at five evenly spaced sites between the proximal and distal reference sites. The coronary distensibility index and stiffness index β were calculated for each site and averaged for each coronary segment. Maximal distensibility index, standard deviation and the difference between maximal and minimal distensibility indices within each segment were significantly higher in the ACS-related than -unrelated plaques (5.6 ± 2.3 vs. 3.7 ± 1.8, p < 0.001, 2.1 ± 0.9 vs. 1.1 ± 0.6, p < 0.001 and 5.3 ± 2.3 vs. 2.8 ± 1.5, p < 0.001, respectively). Moreover, the difference in the distensibility index between the lesion site of ACS-related plaques and the immediate proximal site was significantly larger (2.88 ± 2.35 vs. 1.17 ± 1.44, p = 0.022) than that in ACS-unrelated plaques. CONCLUSIONS Coronary artery distensibility is longitudinally more heterogeneous in ACS-related than-unrelated plaques, especially between the lesion and the immediate proximal site.
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Vancraeynest D, Pasquet A, Roelants V, Gerber BL, Vanoverschelde JLJ. Imaging the vulnerable plaque. J Am Coll Cardiol 2011; 57:1961-79. [PMID: 21565634 DOI: 10.1016/j.jacc.2011.02.018] [Citation(s) in RCA: 119] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Revised: 02/09/2011] [Accepted: 02/15/2011] [Indexed: 12/27/2022]
Abstract
Cardiovascular diseases are still the primary causes of mortality in the United States and in Western Europe. Arterial thrombosis is triggered by a ruptured atherosclerotic plaque and precipitates an acute vascular event, which is responsible for the high mortality rate. These rupture-prone plaques are called "vulnerable plaques." During the past decades, much effort has been put toward accurately detecting the presence of vulnerable plaques with different imaging techniques. In this review, we provide an overview of the currently available invasive and noninvasive imaging modalities used to detect vulnerable plaques. We will discuss the upcoming challenges in translating these techniques into clinical practice and in assigning them their exact place in the decision-making process.
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Affiliation(s)
- David Vancraeynest
- Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Cliniques, Université Catholique de Louvain, Brussels, Belgium
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Mok MY, Lau CS, Chiu SSH, Tso AWK, Lo Y, Law LSC, Mak KF, Wong WS, Khong PL, Lam KSL. Systemic sclerosis is an independent risk factor for increased coronary artery calcium deposition. ACTA ACUST UNITED AC 2011; 63:1387-95. [DOI: 10.1002/art.30283] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Cosgrove D, Lassau N. Imaging of perfusion using ultrasound. Eur J Nucl Med Mol Imaging 2010; 37 Suppl 1:S65-85. [PMID: 20640418 DOI: 10.1007/s00259-010-1537-7] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Ultrasound can be used to image perfusion in two ways: the traditional one using Doppler and the more recent using microbubble contrast agents. Doppler is simple to use and inexpensive but is limited to larger vessels with faster flow rates. It cannot interrogate the microvasculature because bulk tissue movement is faster than capillary flow. It has been used for liver and tumour flow. Contrast studies are much richer and can assess both the macro- and microcirculation. One approach analyses the time-intensity curves in a region of interest, e.g. a tumour, myocardium, brain, following bolus i.v. injection. Another approach measures the time taken for the microbubbles to cross a vascular bed of interest. These arrival times can be useful for the liver in both diffuse and focal diseases and for the kidney. Features derived from time-intensity curves following bolus i.v. injections of microbubbles form sensitive early indicators of the vascular response of tumours to antivascular drugs. This approach, known as dynamic contrast-enhanced ultrasound (DCE-US), has been accepted as a valid technique for monitoring tumour response by several authorities.
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Affiliation(s)
- David Cosgrove
- Imaging Sciences Department, Imperial College, Hammersmith Hospital, London, UK.
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21
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Brar SS, Mintz GS, Maehara A, Stone GW. Applications of grayscale and radiofrequency intravascular ultrasound to image atherosclerotic plaque. J Nucl Cardiol 2010; 17:913-27. [PMID: 20706816 DOI: 10.1007/s12350-010-9280-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Somjot S Brar
- Regional Cardiac Catheterization Lab, Kaiser Permanente, Los Angeles, CA, USA
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22
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Gonzalo N, Serruys PW, Okamura T, Shen ZJ, Garcia-Garcia HM, Onuma Y, van Geuns RJ, Ligthart J, Regar E. Relation between plaque type and dissections at the edges after stent implantation: an optical coherence tomography study. Int J Cardiol 2010; 150:151-5. [PMID: 20466444 DOI: 10.1016/j.ijcard.2010.03.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2009] [Revised: 02/16/2010] [Accepted: 03/29/2010] [Indexed: 11/19/2022]
Abstract
BACKGROUND Stent implantation can create vessel damage such as edge dissections. The objectives were i) to evaluate the frequency of edge dissections after stenting visible by intracoronary optical coherence tomography (OCT) in comparison with angiography. ii) to assess with OCT the plaque type left at the stent edges after implantation, and iii) to study whether there is an association between plaque type and dissections at stent edges. METHODS Seventy-three consecutive patients (80 vessels) with OCT post-stent implantation were included in the study. By OCT, plaque type at stent edges and presence of edge dissection were assessed. Angiograms were analyzed by two independent observers to assess the presence of edge dissections. RESULTS Distal and proximal edges were visible by OCT in 72/80 and 45/80 vessels respectively. OCT and angiography agreed in the detection of 7 dissections at distal edge (κ=0.32) and 1 dissection at proximal edge (κ=0.22). Plaque type at distal edge was: fibrotic 55.6%, fibrocalcific 22.2%, fibroatheroma 15.3% and thin-cap fibroatheroma (TCFA) 6.9%. At proximal edge plaque type was: fibrotic 31.1%, fibrocalcific 33.3%, fibroatheroma 28.9% and TCFA 6.7%. In the distal edge, presence of edge dissection was significantly more frequent when the plaque type at the edge was fibrocalcific (43.8%) or lipid rich (37.5%) than when the plaque was fibrous (10%) p=0.009. CONCLUSIONS OCT showed higher sensitivity compared to angiography for the identification of edge dissections. A high proportion of patients showed lipid-rich plaques at stent edges. Plaque type at the stent edges has impact on the presence of edge dissections.
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Schinkel AFL, Krueger CG, Tellez A, Granada JF, Reed JD, Hall A, Zang W, Owens C, Kaluza GL, Staub D, Coll B, ten Cate FJ, Feinstein SB. Contrast-enhanced ultrasound for imaging vasa vasorum: comparison with histopathology in a swine model of atherosclerosis. EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY 2010; 11:659-64. [DOI: 10.1093/ejechocard/jeq048] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Koh AS, Chia S. Update on Clinical Imaging of Coronary Plaque in Acute Coronary Syndrome. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2010. [DOI: 10.47102/annals-acadmedsg.v39n3p203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Current evidence suggests that understanding coronary artery disease extends beyond identifying and treating traditional risk factors. Progression of coronary plaque contributes to the development of acute coronary syndrome (ACS). In this article, we reviewed current literature for modalities to image coronary plaque as well as discussed the role of emerging techniques that can improve our understanding of the pathophysiology of ACS.
Key words: Coronary disease, Myocardial infarction, Vulnerable plaque
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Abstract
This article provides a systematic approach to vulnerable plaques. It is divided into 4 sections. The first section is devoted to definition, incidence, anatomic distribution, and clinical presentation. The second section is devoted to plaque composition, setting up the foundations to understand plaque vulnerability. The third section relates to invasive plaque imaging. The fourth section is devoted to therapy, from conservative pharmacologic options to aggressive percutaneous coronary intervention alternatives.
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Affiliation(s)
- Pedro R Moreno
- Zena and Michael A. Wiener Cardiovascular Institute and The Marie-Josee and Henry R. Kravis Cardiovascular Health Center, The Mount Sinai School of Medicine, Box 1030, New York, NY 10029, USA.
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26
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Is it a Monet or a Picasso? The problems with “close up” plaque quantitation using MDCT. J Cardiovasc Comput Tomogr 2010; 4:116-8. [DOI: 10.1016/j.jcct.2010.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2010] [Accepted: 03/03/2010] [Indexed: 11/24/2022]
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Gonzalo N, Serruys PW, Barlis P, Ligthart J, Garcia-Garcia HM, Regar E. Multi-modality intra-coronary plaque characterization: A pilot study. Int J Cardiol 2010; 138:32-9. [DOI: 10.1016/j.ijcard.2008.08.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2008] [Revised: 06/04/2008] [Accepted: 08/08/2008] [Indexed: 10/21/2022]
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Is size really all that matters? Remarks on size and necrotic core content of atherosclerotic plaques. Int J Cardiovasc Imaging 2009; 26:173-6. [PMID: 20043242 PMCID: PMC2831179 DOI: 10.1007/s10554-009-9557-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2009] [Accepted: 12/04/2009] [Indexed: 11/02/2022]
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Lee WS, Kim SW, Ryu WS. Progression and observational frequency of atheromatous plaques in autopsied coronary arteries. Korean Circ J 2009; 39:399-407. [PMID: 19949584 PMCID: PMC2771793 DOI: 10.4070/kcj.2009.39.10.399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2009] [Revised: 03/23/2009] [Accepted: 03/26/2009] [Indexed: 11/30/2022] Open
Abstract
Background and Objectives Virtual histology-intravascular ultrasound (VH-IVUS) studies on early-stage fibroatheroma, the probable precursor lesion of progression to thin-cap fibroatheroma (TCFA), have only rarely been done in man. We investigated the progression and observational frequency of fibroatheromas, and compared plaque components between early-stage and advance-staged fibroatheromas in the general population. Subjects and Methods We assessed coronary fibroatheromas using VH-IVUS and histopathologic analysis of 109 coronary lesions from 40 autopsied cases that were not due to sudden cardiac death (NSCD cases). Fibroatheromas were grouped into early fibroatheroma, late fibroatheroma, thick-cap fibroatheroma (TkCFA), and thin-cap fibroatheroma. Results Mean patient age was 45±11 years old and 71% were males. Of 109 lesions, 27% were early fibroatheromas, 53% late fibroatheromas, 9% TkCFA, and 11% TCFA. VH-IVUS showed that there was relatively less fibrotic and fibrofatty plaque and more dense calcium deposits as fibroatheromas progressed. Furthermore, the relative amounts of fibrotic and fibrofatty plaque decreased (r=0.773, p<0.001 and r=0.538, p<0.001, respectively) as the necrotic core increased, while the relative area of dense calcium increased (r=0.665, p<0.001) as the size of the necrotic core increased. Conclusion Of NSCD cases in Korea, 27% were early fibroatheromas, 53% were late fibroatheromas, 9% were TkCFA, and 11% were TCFA. Advance-staged fibroatheromas show more necrotic core volume and more dense calcium than small, early-stage fibroatheromas.
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Affiliation(s)
- Wang-Soo Lee
- Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea
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Philipp S, Böse D, Wijns W, Marso SP, Schwartz RS, König A, Lerman A, Garcia-Garcia HM, Serruys PW, Erbel R. Do systemic risk factors impact invasive findings from virtual histology? Insights from the international virtual histology registry. Eur Heart J 2009; 31:196-202. [PMID: 19854730 DOI: 10.1093/eurheartj/ehp428] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
AIMS Cardiovascular risk factors such as elevated serum lipid levels are important in the development of coronary atherosclerosis. Radiofrequency (RF) analysis of intravascular ultrasound [IVUS, Virtual histology (VH)] offers a unique tool to study the composition of coronary atherosclerotic plaque in vivo. We used data from the multicentre VH registry to assess the association between cardiovascular risk factors and coronary plaque volume and composition. METHODS AND RESULTS Between August 2004 and July 2006, 990 patients in 42 centres were enrolled in a prospective, multicentre, non-randomized global VH registry. Coronary artery imaging was performed by conventional IVUS and RF-IVUS. The four RF-IVUS plaque components [dense calcium (DC), necrotic core (NC), fibrous (F) tissue, and fibro fatty (FF)] were analysed in every recorded frame. The results were expressed as mean cross-sectional areas, absolute volume, and percentage of total plaque volume. Risk factor assessment included evaluation of family history of previous myocardial infarction (MI), past or current smoking, diabetes mellitus, hypertension, and the laboratory measurements. Patients with diabetes had an increased relative proportion of NC (6.47 +/- 0.28 vs. 5.86 +/- 0.14%, P = 0.037) and DC (4.58 +/- 0.27 vs. 3.90 +/- 0.14%, P = 0.017), and patients with hypertension had an increased relative proportion of FF, DC (4.35 +/- 0.16 vs. 3.57 +/- 0.17%, P = 0.02) and NC (6.24 +/- 0.17 vs. 5.60 +/- 0.19%, P = 0.01). Compared with patients with LDL-C <100 mg/dL, patients with LDL-C >160 mg/dL had higher plaque volume (342.1 +/- 26.2 vs. 318.6 +/- 10.7 mm(3)). Linear regression analysis showed a correlation between the level of HDL-C and F (r = -0.149, P < 0.01), FF (r = -0.106, P < 0.01), and NC (r = -0.90, P < 0.05). The level of LDL correlated with F (r = 0.110, P < 0.01). Patients with prior MI have an increased percentage of F (30.03 +/- 0.59 vs. 28.20 +/- 0.37%, P = 0.009). Smoking had no relevant effect on plaque composition. Treatment with acetylsalicylacid and statins reduced FF with altering plaque volume. CONCLUSION Radiofrequency-IVUS detects marked differences in coronary plaque composition related to the risk factor profile with particular focus on lipid levels. Greater amounts of NC were associated with diabetes, hypertension, MI, and low HDL-C. The effects of treatment of changes related to plaque composition are underway.
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Affiliation(s)
- Sebastian Philipp
- Department of Cardiology, Westgerman Heart Center Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen, Germany.
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Raichlin E, Edwards BS, Kremers WK, Clavell AL, Rodeheffer RJ, Frantz RP, Pereira NL, Daly RC, McGregor CG, Lerman A, Kushwaha SS. Acute cellular rejection and the subsequent development of allograft vasculopathy after cardiac transplantation. J Heart Lung Transplant 2009; 28:320-7. [PMID: 19332257 DOI: 10.1016/j.healun.2009.01.006] [Citation(s) in RCA: 118] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2008] [Revised: 09/15/2008] [Accepted: 01/14/2009] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Cardiac allograft vasculopathy (CAV) is primarily immune-mediated. We investigated the role of cellular rejection in CAV development. METHODS The study comprised 252 cardiac transplant recipients (mean age, 49.02 +/- 17.05 years; mean follow-up, 7.61 +/- 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R = 1, 2R = 2, 3R = 3) and any rejection score (ARS; calculated as 0R = 0, 1R = 1, 2R = 1; 3R = 1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. CAV was defined as coronary stenosis of 40% or more and/or distal pruning of secondary side branches. Thirty-two patients had undergone 3-dimensional intravascular ultrasound (IVUS) at baseline and with virtual histology (VH) IVUS at 24 months. RESULTS In univariate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 0.99-3.90, p = 0.05) and ARS (HR, 2.22; 95% CI, 1.01-4.95; p = 0.047) were associated with increased risk of CAV. In multivariate analysis, 6-month TRS (HR, 2.84; 95% CI, 1.44-6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset (p = 0.018). There was direct correlation (r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core demonstrated by VH-IVUS at 24 months. CONCLUSION Recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.
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Affiliation(s)
- Eugenia Raichlin
- William J. von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota 55905, USA
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Lee WS, Kim SW, Hong SA, Lee TJ, Park ES, Kim HJ, Lee KJ, Kim TH, Kim CJ, Ryu WS. Atherosclerotic progression attenuates the expression of Nogo-B in autopsied coronary artery: pathology and virtual histology intravascular ultrasound analysis. J Korean Med Sci 2009; 24:596-604. [PMID: 19654939 PMCID: PMC2719206 DOI: 10.3346/jkms.2009.24.4.596] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2009] [Accepted: 06/24/2009] [Indexed: 11/20/2022] Open
Abstract
The relation of Nogo-B to atherosclerotic plaque progression is not well understood. Thus, the purpose of this study was to assess the expression of Nogo-B in fibroatheromas (FA) of different stages, classified using virtual histology intravascular ultrasound (VH-IVUS) analysis in 19 autopsied cases of non-sudden cardiac death. VH-IVUS imaging analysis was performed 30 mm from the ostium of each coronary artery. VH-IVUS revealed 11 early FAs (34.5+/-8.3 yr), 12 late FAs (42.6+/-16.6 yr), 8 thick-cap FAs (TkCFAs) (46.4+/-11.1 yr), and 6 thin-cap FAs (TCFAs) (51.8+/-6.8 yr). TkCFAs and TCFAs were defined as advanced FA. FA progression advanced with age (P=0.04). VH-IVUS analysis of small, early FAs showed smaller necrotic cores and relatively less calcium compared to more advanced FAs with large necrotic cores (P<0.001). Histopathology and immunohistochemical stains demonstrated that early or late FAs had smaller necrotic cores, less empty space of decalcification, and greater Nogo-B expression compared to advanced FAs (vs. early FA, P=0.013; vs. late FA, P=0.008, respectively). These findings suggest that FA progression is inversely associated with Nogo-B expression. Local reduction of Nogo-B may contribute to plaque formation and/or instability.
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Affiliation(s)
- Wang-Soo Lee
- Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
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Impact of plaque characteristics analyzed by intravascular ultrasound on long-term clinical outcomes. Am J Cardiol 2009; 103:1221-6. [PMID: 19406263 DOI: 10.1016/j.amjcard.2009.01.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2008] [Revised: 01/05/2009] [Accepted: 01/05/2009] [Indexed: 11/20/2022]
Abstract
Limited data are available on long-term outcomes for vulnerable plaque analyzed by intravascular ultrasound (IVUS). The aim of this study was to investigate long-term clinical outcomes in 183 patients (79 with stable angina pectoris and 104 with acute coronary syndromes) who underwent preintervention 3-vessel IVUS and single-vessel stent implantation. Critical events, defined as any cause of death and acute coronary syndromes during follow-up, were evaluated. Plaque characteristics were analyzed in the target vessel and nontarget vessels. Vulnerable plaques were arbitrarily defined as plaques with rupture, lipid core, dissection, or thrombus. The mean follow-up period was 50 +/- 20 months. Critical events developed in 12 patients (7%; 6 acute coronary syndromes, 6 deaths). The critical event-free rate was not different according to the presence of vulnerable plaques in the target lesion (95% vs 95%, p = 0.86). However, in the nontarget vessels, the long-term critical event-free rate was significantly lower in patients with vulnerable plaques (88% vs 96%, p = 0.04). On multivariate Cox regression analysis, the multiplicity of vulnerable plaques in the nontarget vessels (hazard ratio 2.2, 95% confidence interval 1.4 to 3.4, p = 0.001) was the only independent predictor of long-term critical events. Acute coronary syndromes (odds ratio 5.4, 95% confidence interval 2.1 to 14.3, p = 0.001) and diabetes mellitus (odds ratio 5.2, 95% confidence interval 1.9 to 13.8, p = 0.001) were significantly associated with the multiplicity of vulnerable plaques. In conclusion, the multiplicity of vulnerable plaques in nontarget vessels was the most important predictor of future critical cardiac events in this 3-vessel IVUS study.
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Low A, Kawase Y, Chan YH, Tearney G, Bouma B, Jang IK. In vivo characterisation of coronary plaques with conventional grey-scale intravascular ultrasound: correlation with optical coherence tomography. EUROINTERVENTION 2009; 4:626-32. [DOI: 10.4244/eijv4i5a105] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Cosgrove D, Harvey C. Clinical uses of microbubbles in diagnosis and treatment. Med Biol Eng Comput 2009; 47:813-26. [PMID: 19205774 DOI: 10.1007/s11517-009-0434-3] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2008] [Accepted: 11/20/2008] [Indexed: 12/27/2022]
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Enhancing In-Vitro IVUS Data for Tissue Characterization. PATTERN RECOGNITION AND IMAGE ANALYSIS 2009. [DOI: 10.1007/978-3-642-02172-5_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Böse D, Birgelen C, Zhou XY, Schmermund A, Philipp S, Sack S, Konorza T, Möhlenkamp S, Leineweber K, Kleinbongard P, Wijns W, Heusch G, Erbel R. Impact of atherosclerotic plaque composition on coronary microembolization during percutaneous coronary interventions. Basic Res Cardiol 2008; 103:587-97. [DOI: 10.1007/s00395-008-0745-9] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2007] [Accepted: 08/12/2008] [Indexed: 11/24/2022]
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Abstract
Atherosclerosis is a chronic, progressive, inflammatory disease with a long asymptomatic phase. Disease progression can lead eventually to the occurrence of acute cardiovascular events such as myocardial infarction, unstable angina pectoris and sudden cardiac death. While the disease is still in a subclinical stage, however, the presence of atherosclerosis can be identified by several methods, including coronary angiography, intravascular ultrasonography, B-mode ultrasonography, computed tomography and magnetic resonance imaging. Based on the results of imaging studies, statin therapy can slow, halt or even reverse the progression of atherosclerotic disease, depending on the intensity of treatment. Whether to screen and treat patients for subclinical atherosclerosis remains controversial. Although atheromatous plaque burden reduction has not yet been definitively correlated with significant decreases in risk for acute coronary events in asymptomatic patients, statin therapy contributes significantly to the risk reduction observed in clinical trials in patients with and without overt coronary disease.
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Affiliation(s)
- P P Toth
- Sterling Rock Falls Clinic, Sterling, and University of Illinois College of Medicine, Peoria, IL 61008, USA.
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Alfonso F, Hernando L. Intravascular ultrasound tissue characterization. I like the rainbow but...what's behind the colours? Eur Heart J 2008; 29:1701-3. [PMID: 18559328 DOI: 10.1093/eurheartj/ehn053] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Coronary plaque composition as assessed by greyscale intravascular ultrasound and radiofrequency spectral data analysis. Int J Cardiovasc Imaging 2008; 24:811-8. [DOI: 10.1007/s10554-008-9324-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2007] [Accepted: 05/26/2008] [Indexed: 11/26/2022]
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Prasad A, Cipher DJ, Prasad A, Mohandas A, Roesle M, Brilakis ES, Banerjee S. Reproducibility of intravascular ultrasound virtual histology analysis. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2008; 9:71-7. [DOI: 10.1016/j.carrev.2007.11.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2007] [Revised: 11/03/2007] [Accepted: 11/06/2007] [Indexed: 11/29/2022]
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Young JJ, Phillips HR, Marso SP, Granada JF, McPherson JA, Waksman R, Steinhubl SR, Schwartz RS, Stone GW. Vulnerable plaque intervention: State of the art. Catheter Cardiovasc Interv 2008; 71:367-74. [DOI: 10.1002/ccd.21354] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Auer M, Regitnig P, Stollberger R, Ebner F, Holzapfel GA. A methodology to study the morphologic changes in lesions during in vitro angioplasty using MRI and image processing. Med Image Anal 2007; 12:163-73. [PMID: 17988929 DOI: 10.1016/j.media.2007.09.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2006] [Revised: 08/02/2007] [Accepted: 09/18/2007] [Indexed: 10/22/2022]
Abstract
The assessment of morphologic changes in atherosclerotic lesions during interventional procedures such as transluminal balloon angioplasty is an issue of highest clinical importance. We propose a methodology that allows realistic 3D morphomechanical modeling of the vessel, the plaque and the lumen at different stages of in vitro angioplasty. We elaborate on a novel device designed to guide angioplasty under controlled experimental conditions. The device allows to reproduce in vivo conditions as good as possible, i.e. axial in situ pre-stretch, 100mmHg intraluminal pressure, 37 degrees C Tyrode solution, balloon inflation without external constraints using a high-pressure syringe and contrast medium. With a standard 1.5T MR-system we accomplish multi-spectral images at different stages of the angioplasty experiment. After MR image acquisition the specimen is used for histopathological analysis and biomechanical tests. A segmentation process is used to generate NURBS-based 3D geometric models of the individual vessel and plaque components at different balloon pressures. Tissue components are segmented automatically using generalized gradient vector flow active contours. We investigated 10 human femoral arteries. The effects of balloon compression on the individual artery components is particularly described for two obstructed arteries with an intact collagenous cap, a pronounced lipid pool and with calcification. In both arteries we observe a significant increase in lumen area after angioplasty. Dissection between intima and media and reduction of the lipid pool are primary mechanisms of dilatation. This methodology provides a basis for studying plaque biomechanics under supra-physiological loading conditions. It has the potential to improve and validate finite element models of atherosclerotic plaques which may allow a better prediction of angioplasty procedures.
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Affiliation(s)
- M Auer
- Graz University of Technology, Institute for Biomechanics, Center for Biomedical Engineering, Kronesgasse 5-I, 8010 Graz, Austria
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Cheruvu PK, Finn AV, Gardner C, Caplan J, Goldstein J, Stone GW, Virmani R, Muller JE. Frequency and Distribution of Thin-Cap Fibroatheroma and Ruptured Plaques in Human Coronary Arteries. J Am Coll Cardiol 2007; 50:940-9. [PMID: 17765120 DOI: 10.1016/j.jacc.2007.04.086] [Citation(s) in RCA: 286] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2006] [Revised: 03/13/2007] [Accepted: 04/03/2007] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Our purpose was to quantify the frequency and distribution of suspected vulnerable lesions, defined as thin-capped fibroatheroma (TCFA) and ruptured plaque, in human coronary artery autopsy specimens. BACKGROUND Most acute coronary events and sudden death are believed to arise from rupture of a TCFA followed by thrombosis. Although there is general agreement that clinical events are usually caused by focal lesions, there is considerable debate over the relative importance of focal versus systemic factors in the pathogenesis of atherosclerosis. METHODS We longitudinally sectioned coronary arteries from 50 whole hearts taken from patients (mean age 73 years, 64% men) dying of cardiovascular (n = 33), noncardiovascular (n = 13), and unknown (n = 4) causes. A total of 3,639 longitudinal segments of length 3 mm were sectioned from 148 arteries, accounting for 10.9 m of total tissue length. Specimens were classified on the basis of histology and computer-aided morphometry. RESULTS Twenty-three TCFA and 19 ruptured plaques were found (mean +/- SD: 0.46 +/- 0.95 and 0.38 +/- 0.70 per heart, respectively), and these lesions accounted for only 1.6% and 1.2%, respectively, of the total length of the coronary tree examined in patients dying of cardiovascular causes. The majority of TCFA and ruptured plaque localized in the proximal third of the major coronary arteries, and in 92% of cases these lesions clustered within 2 or fewer nonoverlapping 20-mm segments. CONCLUSIONS The suspected precursors of rupture-mediated thrombosis occur in a limited, focal distribution in the coronary arteries.
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Broz P, Marsch S, Hunziker P. Targeting of Vulnerable Plaque Macrophages with Polymer-Based Nanostructures. Trends Cardiovasc Med 2007; 17:190-6. [PMID: 17662913 DOI: 10.1016/j.tcm.2007.05.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2007] [Revised: 05/04/2007] [Accepted: 05/09/2007] [Indexed: 11/19/2022]
Abstract
Macrophages are key cellular elements of atherosclerotic plaque pathogenesis and are a significant risk factor for plaque rupture. Current diagnostic techniques for the detection of plaque macrophages are often limited by insufficient sensitivity and selectivity and have not reached broad clinical practice until now. Supramolecular nanometer-sized structures such as conjugates, nanoparticles, micelles, or vesicles built from novel polymers promise to be useful in cell-specific delivery and may be of particular value for the detection and treatment of vulnerable plaque macrophages. Key properties of polymer-based nanostructures are high stability, improved biocompatibility, long circulation half-lives, defined biodegradation, targeting moieties, and triggerable controlled release. This review gives an insight into several promising research projects with polymer-based nanostructures for macrophage detection or treatment that might enter cardiologic practice in the near future.
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Affiliation(s)
- Pavel Broz
- Medical Intensive Care Unit, University Hospital Basel, 4031 Basel, Switzerland.
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Abstract
With technical improvements in catheter designs, intravascular ultrasound (IVUS) imaging of coronary arteries has become a routine procedure in most cardiac catheterization laboratories. In clinical practice, IVUS imaging of the coronary arteries is commonly performed to answer specific clinical questions such as the evaluation of an indeterminate narrowing of the left main coronary artery. In recent years, IVUS is also being performed as an endpoint for drug treatment trials in the assessment of atherosclerosis progression and/or regression. In this review we will focus on how validation studies of coronary IVUS systems have advanced our ability to use this powerful imaging tool and understand IVUS images, how acoustic and geometric factors affect proposed image processing tools and illustrate some current clinical uses of coronary IVUS.
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Affiliation(s)
- Charles R McKay
- Division of Cardiology, Harbor UCLA Medical Center, Torrance, CA 90502, USA.
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Böse D, von Birgelen C, Erbel R. Intravascular ultrasound for the evaluation of therapies targeting coronary atherosclerosis. J Am Coll Cardiol 2007; 49:925-32. [PMID: 17336714 DOI: 10.1016/j.jacc.2006.08.067] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2006] [Revised: 08/21/2006] [Accepted: 08/26/2006] [Indexed: 10/23/2022]
Abstract
Many cardiovascular events are clinical manifestations of underlying atherosclerotic disease. The progression of atherosclerosis, traditionally measured by angiography, is predictive of future clinical events and is a valid surrogate marker of cardiovascular (CV) disease. There is growing interest in using novel surrogate end points in clinical trials to expedite the development of new CV therapies. Innovative imaging technologies, such as intravascular ultrasound (IVUS), may carry advantages for the evaluation of coronary atherosclerotic burden and disease progression. Unlike angiography, which displays only the opacified luminal "silhouette," IVUS provides transmural imaging of the entire arterial wall and permits both detection of early-stage atherosclerosis and accurate cross-sectional and even 3-dimensional quantification of plaques. Intravascular ultrasound is now used to guide therapeutic interventions and for diagnostic purposes, primarily for the evaluation of ambiguous lesions and left main coronary artery disease. In addition, clinical studies are using IVUS serially to measure plaque progression, which appears to be related to future CV events. Although the probative force of clinical end point studies still is stronger, IVUS is catching up. Currently, several trials of CV therapies use IVUS-determined plaque progression as the end point. The rationale for using IVUS-based surrogate end points in clinical trials is discussed in the present review. Key advantages of using IVUS-based surrogate end points versus clinical outcome include smaller patient numbers and substantially shorter trial durations; this reduces costs and may expedite the development and testing of new drugs. We expect in the near future a further increase of the use of IVUS-based surrogate end points in trials that evaluate novel CV therapies targeting on coronary atherosclerosis.
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Affiliation(s)
- Dirk Böse
- Department of Cardiology, University of Duisburg-Essen, Essen, Germany
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Choi SH, Chae A, Chen CH, Merki E, Shaw PX, Tsimikas S. Emerging approaches for imaging vulnerable plaques in patients. Curr Opin Biotechnol 2007; 18:73-82. [PMID: 17234398 DOI: 10.1016/j.copbio.2007.01.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2006] [Revised: 11/10/2006] [Accepted: 01/05/2007] [Indexed: 01/03/2023]
Abstract
The diagnosis of vulnerable plaques, which have the propensity to develop atherothrombosis, remains an elusive goal in clinical medicine. The most accepted features of vulnerable plaques, such as a large lipid core, increased inflammatory milieu and thin fibrous caps, have been well characterized through pathological studies. The ability to image a vulnerable plaque in susceptible patients would theoretically result in useful prognostic information that can be used to either monitor or treat patients at risk more aggressively. Several invasive techniques, such as integrated backscatter, virtual histology, palpography, optical coherence tomography and thermal heterogeneity, have been validated ex vivo and are now being evaluated in clinical studies. Non-invasive techniques, such as nuclear imaging, show promise in identifying increased metabolic activity and characteristic features of vulnerable plaques in patients. Natural history and intervention studies will need to be performed to determine whether identifying and treating vulnerable plaques will lead to improved clinical outcomes.
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Affiliation(s)
- Seung-Hyuk Choi
- Division of Cardiology, University of California San Diego, La Jolla, USA
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