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Maes L, Versweyveld L, Evans NR, McCabe JJ, Kelly P, Van Laere K, Lemmens R. Novel Targets for Molecular Imaging of Inflammatory Processes of Carotid Atherosclerosis: A Systematic Review. Semin Nucl Med 2024; 54:658-673. [PMID: 37996309 DOI: 10.1053/j.semnuclmed.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/20/2023] [Accepted: 10/23/2023] [Indexed: 11/25/2023]
Abstract
Computed tomography angiography (CTA), magnetic resonance angiography (MRA) and 18F-FDG-PET have proven clinical value when evaluating patients with carotid atherosclerosis. In this systematic review, we will focus on the role of novel molecular imaging tracers in that assessment and their potential strengths to stratify stroke risk. We systematically searched PubMed, Embase, the Web of Science Core Collection, and Cochrane Library for articles reporting on molecular imaging to noninvasively detect or characterize inflammation in carotid atherosclerosis. As our focus was on nonclassical novel targets, we omitted reports solely on 18F-FDG and 18F-NaF. We summarized and mapped the selected studies to provide an overview of the current clinical development in molecular imaging in relation to risk factors, imaging and histological findings, diagnostic and prognostic performance. We identified 20 articles in which the utilized tracers to visualize carotid wall inflammation were somatostatin subtype-2- (SST2-) (n = 5), CXC-motif chemokine receptor 4- (CXCR4-) (n = 3), translocator protein- (TSPO-) (n = 2) and aVβ3 integrin-ligands (n = 2) and choline-tracers (n = 2). Tracer uptake correlated with traditional cardiovascular risk factors, that is, age, gender, diabetes, hypercholesterolemia, and hypertension as well as prior cardiovascular disease. We identified discrepancies between tracer uptake and grade of stenosis, plaque calcification, and 18F-FDG uptake, suggesting the importance of alternative characterization of atherosclerosis beyond classical neuroimaging features. Immunohistochemical analysis linked tracer uptake to markers of macrophage infiltration and neovascularization. Symptomatic carotid arteries showed higher uptake compared to asymptomatic (including contralateral, nonculprit) arteries. Some studies demonstrated a potential role of these novel molecular imaging as a specific intermediary (bio)marker for outcome. Several novel tracers show promise for identification of high-risk plaque inflammation. Based on the current evidence we cautiously propose the SST2-ligands and the choline radiotracers as viable candidates for larger prospective longitudinal outcome studies to evaluate their predictive use in clinical practice.
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Affiliation(s)
- Louise Maes
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology, KULeuven - University of Leuven, Leuven, Belgium.
| | - Louis Versweyveld
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology, KULeuven - University of Leuven, Leuven, Belgium
| | - Nicholas R Evans
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - John J McCabe
- Health Research Board (HRB), Stroke Clinical Trials Network Ireland (SCTNI), Dublin, Ireland; School of Medicine, University College Dublin (UCD), Dublin, Ireland; Department of Geriatric Medicine, Mater Misericordiae University Hospital Dublin, Dublin, Ireland
| | - Peter Kelly
- Health Research Board (HRB), Stroke Clinical Trials Network Ireland (SCTNI), Dublin, Ireland; School of Medicine, University College Dublin (UCD), Dublin, Ireland; Mater Misericordiae University Hospital Dublin, Stroke Service, Dublin, Ireland
| | - Koen Van Laere
- Division of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium; Department of Imaging and Pathology, KULeuven - University of Leuven - Nuclear Medicine and Molecular Imaging, Leuven, Belgium
| | - Robin Lemmens
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology, KULeuven - University of Leuven, Leuven, Belgium
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2
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Saba L, Loewe C, Weikert T, Williams MC, Galea N, Budde RPJ, Vliegenthart R, Velthuis BK, Francone M, Bremerich J, Natale L, Nikolaou K, Dacher JN, Peebles C, Caobelli F, Redheuil A, Dewey M, Kreitner KF, Salgado R. State-of-the-art CT and MR imaging and assessment of atherosclerotic carotid artery disease: the reporting-a consensus document by the European Society of Cardiovascular Radiology (ESCR). Eur Radiol 2023; 33:1088-1101. [PMID: 36194266 PMCID: PMC9889425 DOI: 10.1007/s00330-022-09025-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 06/26/2022] [Accepted: 06/30/2022] [Indexed: 02/04/2023]
Abstract
The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society's highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. The purpose of this second document is to discuss suggestions for standardized reporting based on the accompanying consensus document part I. KEY POINTS: • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • The information in the report must cover vessel morphology, description of stenosis, and plaque imaging features. • A structured approach to reporting ensures that all essential information is delivered in a standardized and consistent way to the referring clinician.
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Affiliation(s)
- Luca Saba
- Department of Radiology, University of Cagliari, Cagliari, Italy
| | - Christian Loewe
- Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Thomas Weikert
- Department of Radiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Michelle C Williams
- BHF Centre for Cardiovascular Science, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH164SB, UK
- Edinburgh Imaging Facility QMRI, University of Edinburgh, Edinburgh, UK
| | - Nicola Galea
- Policlinico Umberto I, Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Ricardo P J Budde
- Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - Rozemarijn Vliegenthart
- Department of Radiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713, GZ, Groningen, The Netherlands
| | - Birgitta K Velthuis
- Department of Radiology, Utrecht University Medical Center, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Marco Francone
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Jens Bremerich
- Department of Radiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Luigi Natale
- Department of Radiological Sciences - Institute of Radiology, Catholic University of Rome, "A. Gemelli" University Hospital, Rome, Italy
| | - Konstantin Nikolaou
- Department of Diagnostic and Interventional Radiology, University of Tuebingen, Tübingen, Germany
| | - Jean-Nicolas Dacher
- Department of Radiology, Normandie University, UNIROUEN, INSERM U1096 - Rouen University Hospital, F 76000, Rouen, France
| | - Charles Peebles
- Department of Cardiothoracic Radiology, University Hospital Southampton, Southampton, UK
| | - Federico Caobelli
- University Clinic of Nuclear Medicine Inselspital Bern, University of Bern, Bern, Switzerland
| | - Alban Redheuil
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Department of Cardiovascular and Thoracic, Imaging and Interventional Radiology, Institute of Cardiology, APHP, Pitié-Salpêtrière University Hospital, Paris, France
- Laboratoire d'Imagerie Biomédicale, Sorbonne Universités, UPMC Univ Paris 06, INSERM 1146, CNRS 7371, Paris, France
| | - Marc Dewey
- Department of Radiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1371, 10117 Berlin, Germany
| | - Karl-Friedrich Kreitner
- Department of Diagnostic and Interventional Radiology, University Medical Center, Mainz Langenbeckstraße 1, 55131, Mainz, Germany
| | - Rodrigo Salgado
- Department of Radiology, Antwerp University Hospital & Antwerp University, Holy Heart Lier, Berlaar, Belgium.
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Engel LC, Landmesser U, Abdelwahed YS, Gigengack K, Wurster T, Manes C, Skurk C, Lauten A, Schuster A, Noutsias M, Hamm B, Botnar RM, Bigalke B, Makowski MR. In vivo assessment of endothelial permeability of coronary lesions with variable degree of stenosis using an albumin-binding MR probe. Int J Cardiovasc Imaging 2021; 37:3049-3055. [PMID: 34247318 PMCID: PMC8494683 DOI: 10.1007/s10554-021-02293-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 05/17/2021] [Indexed: 10/29/2022]
Abstract
MR imaging with an albumin-binding probe enables the visualization of endothelial permeability and damage in the arterial system. The goal of this study was to compare signal enhancement of lesions with different grades of stenosis segments on molecular CMR in combination with the albumin-binding probe gadofosveset. This prospective clinical study included patients with symptoms suggestive of coronary artery disease (CAD). Patients underwent gadofosveset-enhanced cardiovascular magnetic resonance (CMR) imaging and x-ray angiography (QCA) within 24 h. CMR imaging was performed prior to and 24 h following the administration of gadofosveset. Contrast-to-noise ratios (CNRs) between segments with different grades of stenosis were compared. Overall, n = 203 segments of 26 patients were included. Lesions with more than > 70% stenosis demonstrated significantly higher CNRs compared to lesions < 70% (7.6 ± 8.3 vs. 2.5 ± 4.9; p < 0.001). Post-stenotic segments of lesions > 70% stenosis showed significant higher signal enhancement compared to segments located upstream of these lesions (7.3 ± 8.8 vs. 2.8 ± 2.2; p = 0.02). No difference in signal enhancement between segments proximal and distal of lesions with stenosis greater than 50% was measured (3.3 ± 2.8 vs. 2.4 ± 2.7; p = 0.18). ROC analysis for the detection of lesions ≥ 70% revealed an area under the curve of 0.774 (95% CI 0.681-0.866). This study suggests that relevant coronary stenosis and their down-stream segments are associated with increased signal enhancement on Gadofosveset-enhanced CMR, suggesting a higher endothelial permeability in these lesions. An albumin-binding MR probe could represent a novel in vivo biomarker for the identification and characterization of these vulnerable coronary segments.
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Affiliation(s)
- Leif-Christopher Engel
- Department of Cardiology, German Heart Center, Munich, Germany. .,Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany. .,Berlin Institute of Health (BIH), Berlin, Germany.
| | - Ulf Landmesser
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
| | - Youssef S Abdelwahed
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Kevin Gigengack
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Thomas Wurster
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Costantia Manes
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Carsten Skurk
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Alexander Lauten
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Schuster
- Department of Cardiology and Pulmonology, German Centre for Cardiovascular Research (DZHKPartner Site), Göttingen, Germany.,Department of Cardiology, Royal North Shore Hospital, The Kolling Institute, Northern Clinical School, University of Sydney, 5th Floor, Acute Services Building, Reserve Road, St Leonard's, Sydney, NSW, Australia
| | - Michel Noutsias
- Mid-German Heart Center, Department of Internal Medicine III (KIM-III), Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle-Wittenberg, Halle (Saale), Germany
| | - Bernd Hamm
- Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Rene M Botnar
- Escuela de Ingeniería, Pontificia Universidad Católica de Chile, Santiago, Chile.,Division of Imaging Sciences and Biomedical Engineering, King's College London, London, UK
| | - Boris Bigalke
- Department of Cardiology, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Marcus R Makowski
- Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Department of Radiology, Klinikum Rechts Der Isar, TU München, München, Germany
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Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model. CONTRAST MEDIA & MOLECULAR IMAGING 2021; 2021:9999847. [PMID: 34007253 PMCID: PMC8099506 DOI: 10.1155/2021/9999847] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/12/2021] [Accepted: 04/19/2021] [Indexed: 11/18/2022]
Abstract
Background Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE-/- model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods Nine ApoE-/- mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE-/- animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results In a previous study, we found that approximately 25% of angiotensin II-infused ApoE-/- mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE-/- mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE-/- mice showed significantly lower contrast-to-noise (CNR) values (p=0.017) in MRI compared to ApoE-/- mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R 2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.
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Kassem M, Florea A, Mottaghy FM, van Oostenbrugge R, Kooi ME. Magnetic resonance imaging of carotid plaques: current status and clinical perspectives. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1266. [PMID: 33178798 PMCID: PMC7607136 DOI: 10.21037/atm-2020-cass-16] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Rupture of a vulnerable carotid plaque is one of the leading causes of stroke. Carotid magnetic resonance imaging (MRI) is able to visualize all the main hallmarks of plaque vulnerability. Various MRI sequences have been developed in the last two decades to quantify carotid plaque burden and composition. Often, a combination of multiple sequences is used. These MRI techniques have been extensively validated with histological analysis of carotid endarterectomy specimens. High agreement between the MRI and histological measures of plaque burden, intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC) status, inflammation and neovascularization has been demonstrated. Novel MRI sequences allow to generate three-dimensional isotropic images with a large longitudinal coverage. Other new sequences can acquire multiple contrasts using a single sequence leading to a tremendous reduction in scan time. IPH can be easily identified as a hyperintense signal in the bulk of the plaque on strongly T1-weighted images, such as magnetization-prepared rapid acquisition gradient echo images, acquired within a few minutes with a standard neurovascular coil. Carotid MRI can also be used to evaluate treatment effects. Several meta-analyses have demonstrated a strong predictive value of IPH, LRNC, thinning or rupture of the FC for ischemic cerebrovascular events. Recently, in a large meta-analysis based on individual patient data of asymptomatic and symptomatic individuals with carotid artery stenosis, it was shown that IPH on MRI is an independent risk predictor for stroke, stronger than any known clinical risk parameter. Expert recommendations on carotid plaque MRI protocols have recently been described in a white paper. The present review provides an overview of the current status and applications of carotid plaque MR imaging and its future potential in daily clinical practice.
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Affiliation(s)
- Mohamed Kassem
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.,Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Alexandru Florea
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,Department of Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany
| | - Felix M Mottaghy
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,Department of Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany
| | - Robert van Oostenbrugge
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.,Department of Neurology, MUMC+, Maastricht, The Netherlands
| | - M Eline Kooi
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.,Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
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Lavin Plaza B, Phinikaridou A, Andia ME, Potter M, Lorrio S, Rashid I, Botnar RM. Sustained Focal Vascular Inflammation Accelerates Atherosclerosis in Remote Arteries. Arterioscler Thromb Vasc Biol 2020; 40:2159-2170. [PMID: 32673527 PMCID: PMC7447189 DOI: 10.1161/atvbaha.120.314387] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. Approach and Results: We used a novel ApoE-/- knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions-pravastatin and minocycline-had distinct anti-inflammatory effects at the plaque and systemic level. CONCLUSIONS We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagen-poor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.
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Affiliation(s)
- Begoña Lavin Plaza
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (B.L.P., A.P., M.P., S.L., I.R., R.M.B.)
| | - Alkystis Phinikaridou
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (B.L.P., A.P., M.P., S.L., I.R., R.M.B.)
| | - Marcelo E Andia
- Radiology Department & Millennium Nucleus for Cardiovascular Magnetic Resonance (M.E.A.), Pontificia Universidad Católica de Chile
| | - Myles Potter
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (B.L.P., A.P., M.P., S.L., I.R., R.M.B.)
| | - Silvia Lorrio
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (B.L.P., A.P., M.P., S.L., I.R., R.M.B.)
| | - Imran Rashid
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (B.L.P., A.P., M.P., S.L., I.R., R.M.B.).,Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH (I.R.)
| | - Rene M Botnar
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (B.L.P., A.P., M.P., S.L., I.R., R.M.B.).,Escuela de Ingeniería (R.M.B.), Pontificia Universidad Católica de Chile
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Noninvasive imaging of vascular permeability to predict the risk of rupture in abdominal aortic aneurysms using an albumin-binding probe. Sci Rep 2020; 10:3231. [PMID: 32094414 PMCID: PMC7039902 DOI: 10.1038/s41598-020-59842-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 01/27/2020] [Indexed: 11/09/2022] Open
Abstract
Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.
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Engel LC, Landmesser U, Abdelwahed YS, Jaguszewski M, Gigengack K, Wurster TH, Skurk C, Manes C, Schuster A, Noutsias M, Hamm B, Botnar RM, Makowski MR, Bigalke B. Comprehensive multimodality characterization of hemodynamically significant and non-significant coronary lesions using invasive and noninvasive measures. PLoS One 2020; 15:e0228292. [PMID: 32004345 PMCID: PMC6994007 DOI: 10.1371/journal.pone.0228292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 01/10/2020] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND There is limited knowledge about morphological molecular-imaging-derived parameters to further characterize hemodynamically relevant coronary lesions. OBJECTIVE The aim of this study was to describe and differentiate specific parameters between hemodynamically significant and non-significant coronary lesions using various invasive and non-invasive measures. METHODS This clinical study analyzed patients with symptoms suggestive of coronary artery disease (CAD) who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-angiography). Hemodynamically significant lesions were defined as lesions with a QFR <0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability, respectively. RESULTS Overall 29 coronary segments from 14 patients were examined. Segments containing lesions with a QFR <0.8 (n = 9) were associated with significantly higher signal enhancement on Gadofosveset-enhanced CMR as compared to segments containing a lesions without significant stenosis (lesion-QFR>0.8; n = 19) (5.32 (4.47-7.02) vs. 2.42 (1.04-5.11); p = 0.042). No differences in signal enhancement were seen on native T1-weighted CMR (2.2 (0.68-6.75) vs. 2.09 (0.91-6.57), p = 0.412). 66.7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions. CONCLUSION The findings of this pilot study suggest that signal enhancement on albumin-binding probe-enhanced CMR but not on T1-weighted CMR is associated with hemodynamically relevant coronary lesions.
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Affiliation(s)
- Leif-Christopher Engel
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
- Klinik für kardiovaskuläre Erkrankungen, Deutsches Herzzentrum München (DHM), Germany
| | - Ulf Landmesser
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - Youssef S. Abdelwahed
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
| | - Milosz Jaguszewski
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
- Medical University of Gdansk, Gdańsk, Poland
| | - Kevin Gigengack
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
| | - Thomas-Heinrich Wurster
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
| | - Carsten Skurk
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
| | - Costantina Manes
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
| | - Andreas Schuster
- Department of Cardiology and Pulmonology, Georg-August-University, Göttingen, Germany
- Department of Cardiology, Royal North Shore Hospital, The Kolling Institute, Northern Clinical School, University of Sydney, 5th Floor, Acute Services Building, Reserve Road, St Leonard's, Sydney, Australia
| | - Michel Noutsias
- Mid-German Heart Center, Department of Internal Medicine III (KIM-III), Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle-Wittenberg, Mid-German Heart Center, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Bernd Hamm
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Radiologie, Berlin
| | - Rene M. Botnar
- King's College London, Division of Imaging Sciences and Biomedical Engineering, London, England, United Kingdom
- Pontificia Universidad Católica de Chile, Escuela de Ingeniería, Santiago, Chile, Germany
| | - Marcus R. Makowski
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Radiologie, Berlin
| | - Boris Bigalke
- Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Klinik für Kardiologie, Berlin, Germany
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Hajhosseiny R, Bahaei TS, Prieto C, Botnar RM. Molecular and Nonmolecular Magnetic Resonance Coronary and Carotid Imaging. Arterioscler Thromb Vasc Biol 2020; 39:569-582. [PMID: 30760017 DOI: 10.1161/atvbaha.118.311754] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Atherosclerosis is the leading cause of cardiovascular morbidity and mortality. Over the past 2 decades, increasing research attention is converging on the early detection and monitoring of atherosclerotic plaque. Among several invasive and noninvasive imaging modalities, magnetic resonance imaging (MRI) is emerging as a promising option. Advantages include its versatility, excellent soft tissue contrast for plaque characterization and lack of ionizing radiation. In this review, we will explore the recent advances in multicontrast and multiparametric imaging sequences that are bringing the aspiration of simultaneous arterial lumen, vessel wall, and plaque characterization closer to clinical feasibility. We also discuss the latest advances in molecular magnetic resonance and multimodal atherosclerosis imaging.
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Affiliation(s)
- Reza Hajhosseiny
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (R.H., T.S.B., C.P., R.M.B.).,National Heart and Lung Institute, Imperial College London, United Kingdom (R.H.)
| | - Tamanna S Bahaei
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (R.H., T.S.B., C.P., R.M.B.)
| | - Claudia Prieto
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (R.H., T.S.B., C.P., R.M.B.).,Escuela de Ingeniería, Pontificia Universidad Catolica de Chile, Santiago, Chile (C.P., R.M.B.)
| | - René M Botnar
- From the School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom (R.H., T.S.B., C.P., R.M.B.).,Escuela de Ingeniería, Pontificia Universidad Catolica de Chile, Santiago, Chile (C.P., R.M.B.)
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10
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Fayad ZA, Swirski FK, Calcagno C, Robbins CS, Mulder W, Kovacic JC. Monocyte and Macrophage Dynamics in the Cardiovascular System: JACC Macrophage in CVD Series (Part 3). J Am Coll Cardiol 2019; 72:2198-2212. [PMID: 30360828 DOI: 10.1016/j.jacc.2018.08.2150] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 07/16/2018] [Accepted: 08/03/2018] [Indexed: 12/12/2022]
Abstract
It has long been recognized that the bone marrow is the primary site of origin for circulating monocytes that may later become macrophages in atherosclerotic lesions. However, only in recent times has the complex relationship among the bone marrow, monocytes/macrophages, and atherosclerotic plaques begun to be understood. Moreover, the systemic nature of these interactions, which also involves additional compartments such as extramedullary hematopoietic sites (i.e., spleen), is only just becoming apparent. In parallel, progressive advances in imaging and cell labeling techniques have opened new opportunities for in vivo imaging of monocyte/macrophage trafficking in atherosclerotic lesions and at the systemic level. In this Part 3 of a 4-part review series covering the macrophage in cardiovascular disease, the authors intersect systemic biology with advanced imaging techniques to explore monocyte and macrophage dynamics in the cardiovascular system, with an emphasis on how events at the systemic level might affect local atherosclerotic plaque biology.
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Affiliation(s)
- Zahi A Fayad
- Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Filip K Swirski
- Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Claudia Calcagno
- Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Clinton S Robbins
- Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Peter Munk Cardiac Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Willem Mulder
- Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jason C Kovacic
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
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11
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Red Wine Grape Pomace Attenuates Atherosclerosis and Myocardial Damage and Increases Survival in Association with Improved Plasma Antioxidant Activity in a Murine Model of Lethal Ischemic Heart Disease. Nutrients 2019; 11:nu11092135. [PMID: 31500172 PMCID: PMC6770693 DOI: 10.3390/nu11092135] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 08/29/2019] [Accepted: 09/02/2019] [Indexed: 12/11/2022] Open
Abstract
A healthy dietary pattern and high quality nutrient intake reduce atherosclerotic cardiovascular disease risk. Red wine grape pomace (RWGP)—a rich natural source of dietary fiber and antioxidants—appears to be a potential functional food ingredient. The impact of a dietary supplementation with RWGP flour was evaluated in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice, a model of lethal ischemic heart disease. SR-B1 KO/ApoER61h/h mice were fed with atherogenic (high fat, cholesterol, and cholic acid, HFC) diet supplemented with: (a) 20% chow (HFC-Control), (b) 20% RWGP flour (HFC-RWGP), or (c) 10% chow/10% oat fiber (HFC-Fiber); and survival time was evaluated. In addition, SR-B1 KO/ApoER61h/h mice were fed for 7 or 14 days with HFC-Control or HFC-RWGP diets and plasma lipid levels, inflammation, oxidative damage, and antioxidant activity were measured. Atherosclerosis and myocardial damage were assessed by histology and magnetic resonance imaging, respectively. Supplementation with RWGP reduced premature death, changed TNF-α and IL-10 levels, and increased plasma antioxidant activity. Moreover, decreased atheromatous aortic and brachiocephalic plaque sizes and attenuated myocardial infarction and dysfunction were also observed. These results suggest that RWGP flour intake may be used as a non-pharmacological therapeutic approach, contributing to decreased progression of atherosclerosis, reduced coronary heart disease, and improved cardiovascular outcomes.
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12
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Crombag GAJC, van Hoof RHM, Holtackers RJ, Schreuder FHBM, Truijman MTB, Schreuder TAHCML, van Orshoven NP, Mess WH, Hofman PAM, van Oostenbrugge RJ, Wildberger JE, Kooi ME. Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast-Enhanced Magnetic Resonance Imaging Study. J Am Heart Assoc 2019; 8:e011832. [PMID: 30971168 PMCID: PMC6507193 DOI: 10.1161/jaha.118.011832] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. The objective of the present study is to investigate whether there is a difference in plaque microvasculature (the volume transfer coefficient Ktrans) between the ipsilateral symptomatic and contralateral asymptomatic carotid plaque using noninvasive dynamic contrast‐enhanced magnetic resonance imaging. Methods and Results Eighty‐eight patients with recent transient ischemic attack or ischemic stroke and ipsilateral >2 mm carotid plaque underwent 3 T magnetic resonance imaging to identify plaque components and to determine characteristics of plaque microvasculature. The volume transfer coefficient Ktrans, indicative for microvascular density, flow, and permeability, was calculated for the ipsilateral and asymptomatic plaque, using a pharmacokinetic model (Patlak). Presence of a lipid‐rich necrotic core, intraplaque hemorrhage, and a thin and/or ruptured fibrous cap was assessed on multisequence magnetic resonance imaging. We found significantly lower Ktrans in the symptomatic carotid plaque compared with the asymptomatic side (0.057±0.002 min−1 versus 0.062±0.002 min−1; P=0.033). There was an increased number of slices with intraplaque hemorrhage (0.9±1.6 versus 0.3±0.8, P=0.002) and lipid‐rich necrotic core (1.4±1.9 versus 0.8±1.4, P=0.016) and a higher prevalence of plaques with a thin and/or ruptured fibrous cap (32% versus 17%, P=0.023) at the symptomatic side. Conclusions Ktrans was significantly lower in symptomatic carotid plaques, indicative for a decrease of plaque microvasculature in symptomatic plaques. This could be related to a larger amount of necrotic tissue in symptomatic plaques. Clinical Trial Registration URL: http://www.clinicaltrials.gov.uk. Unique identifier: NCT01208025.
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Affiliation(s)
- Geneviève A J C Crombag
- 1 Department of Radiology and Nuclear Medicine Maastricht University Medical Centre Maastricht The Netherlands.,4 CARIM School for Cardiovascular Diseases Maastricht University Medical Centre Maastricht The Netherlands
| | - Raf H M van Hoof
- 1 Department of Radiology and Nuclear Medicine Maastricht University Medical Centre Maastricht The Netherlands.,4 CARIM School for Cardiovascular Diseases Maastricht University Medical Centre Maastricht The Netherlands.,5 Control Systems Technology Department of Mechanical Engineering Eindhoven University of Technology Eindhoven The Netherlands
| | - Robert J Holtackers
- 1 Department of Radiology and Nuclear Medicine Maastricht University Medical Centre Maastricht The Netherlands.,4 CARIM School for Cardiovascular Diseases Maastricht University Medical Centre Maastricht The Netherlands
| | - Floris H B M Schreuder
- 6 Department of Neurology Donders Institute for Brain Cognition & Behaviour Radboud University Medical Centre Nijmegen The Netherlands
| | - Martine T B Truijman
- 2 Department of Neurology Maastricht University Medical Centre Maastricht The Netherlands
| | | | | | - Werner H Mess
- 3 Department of Clinical Neurophysiology Maastricht University Medical Centre Maastricht The Netherlands.,4 CARIM School for Cardiovascular Diseases Maastricht University Medical Centre Maastricht The Netherlands
| | - Paul A M Hofman
- 1 Department of Radiology and Nuclear Medicine Maastricht University Medical Centre Maastricht The Netherlands
| | - Robert J van Oostenbrugge
- 2 Department of Neurology Maastricht University Medical Centre Maastricht The Netherlands.,4 CARIM School for Cardiovascular Diseases Maastricht University Medical Centre Maastricht The Netherlands
| | - Joachim E Wildberger
- 1 Department of Radiology and Nuclear Medicine Maastricht University Medical Centre Maastricht The Netherlands.,4 CARIM School for Cardiovascular Diseases Maastricht University Medical Centre Maastricht The Netherlands
| | - M Eline Kooi
- 1 Department of Radiology and Nuclear Medicine Maastricht University Medical Centre Maastricht The Netherlands.,4 CARIM School for Cardiovascular Diseases Maastricht University Medical Centre Maastricht The Netherlands
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13
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Engel LC, Landmesser U, Goehler A, Gigengack K, Wurster TH, Manes C, Girke G, Jaguszewski M, Skurk C, Leistner DM, Lauten A, Schuster A, Noutsias M, Hamm B, Botnar RM, Bigalke B, Makowski MR. Noninvasive Imaging of Endothelial Damage in Patients With Different HbA 1c Levels: A Proof-of-Concept Study. Diabetes 2019; 68:387-394. [PMID: 30487264 DOI: 10.2337/db18-0239] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 11/06/2018] [Indexed: 11/13/2022]
Abstract
The aim of this study was to compare endothelial permeability, which is considered a hallmark of coronary artery disease, between patients with different HbA1c levels using an albumin-binding magnetic resonance (MR) probe. This cross-sectional study included 26 patients with clinical indication for X-ray angiography who were classified into three groups according to HbA1c level (<5.7% [<39 mmol/mol], 5.7-6.4% [39-47 mmol/mol], and ≥6.5% [48 mmol/mol]). Subjects underwent gadofosveset-enhanced coronary magnetic resonance and X-ray angiography including optical coherence within 24 h. Contrast-to-noise ratios (CNRs) were assessed to measure the probe uptake in the coronary wall by coronary segment, excluding those with culprit lesions in X-ray angiography. In the group of patients with HbA1c levels between 5.7 and 6.4%, 0.30 increased normalized CNR values were measured, compared with patients with HbA1c levels <5.7% (0.30 [95% CI 0.04, 0.57]). In patients with HbA1c levels ≥6.5%, we found 0.57 higher normalized CNR values compared with patients with normal HbA1c levels (0.57 [95% CI 0.28, 0.85]) and 0.26 higher CNR values for patients with HbA1c level ≥6.5% compared with patients with HbA1c levels between 5.7 and 6.4% (0.26 [95% CI -0.04, 0.57]). Additionally, late atherosclerotic lesions were more common in patients with high HbA1c levels (HbA1c ≥6.5%, n = 14 [74%]; HbA1c 5.7-6.4%, n = 6 [60%]; and HbA1c <5.7%, n = 10 [53%]). In conclusion, coronary MRI in combination with an albumin-binding MR probe suggests that both patients with intermediate and patients with high HbA1c levels are associated with a higher extent of endothelial damage of the coronary arteries compared with patients with HbA1c levels <5.7%.
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Affiliation(s)
- Leif-Christopher Engel
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health, Berlin, Germany
| | - Ulf Landmesser
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), partner site Berlin, Germany
| | - Alexander Goehler
- Department of Radiology, Brigham's and Women Hospital and Harvard Medical School, Boston, MA
| | - Kevin Gigengack
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Thomas-Heinrich Wurster
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health, Berlin, Germany
| | - Costantina Manes
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Georg Girke
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Milosz Jaguszewski
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Carsten Skurk
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - David M Leistner
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Alexander Lauten
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), partner site Berlin, Germany
| | - Andreas Schuster
- Department of Cardiology and Pulmonology, Georg-August-University, German Centre for Cardiovascular Research (DZHK), partner site Göttingen, Germany
- Department of Cardiology, Royal North Shore Hospital, The Kolling Institute, Nothern Clinical School, University of Sydney, Sydney, Australia
| | - Michel Noutsias
- Mid-German Heart Center, Division of Cardiology, Angiology and Intensive Medical Care, Department of Internal Medicine III, University Hospital Halle, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany
| | - Bernd Hamm
- Klinik für Radiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Rene M Botnar
- Escuela de Ingeniería, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Imaging Sciences and Biomedical Engineering, King's College London, London, U.K
| | - Boris Bigalke
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Marcus R Makowski
- Klinik für Radiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
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14
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Affiliation(s)
- Raphaël Duivenvoorden
- Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (R.D., W.J.M.M.).,Division of Nephrology, Department of Internal Medicine, Amsterdam Cardiovascular Sciences (R.D.)
| | - Willem J M Mulder
- Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (R.D., W.J.M.M.).,Department of Medical Biochemistry (W.J.M.M.), Amsterdam University Medical Centers, Academic Medical Center, The Netherlands.,Laboratory of Chemical Biology Cluster, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, The Netherlands (W.J.M.M.)
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Application of High-Resolution CUBE Sequence in Exploring Stroke Mechanisms of Atherosclerotic Stenosis of Middle Cerebral Artery. J Stroke Cerebrovasc Dis 2018; 28:156-162. [PMID: 30322755 DOI: 10.1016/j.jstrokecerebrovasdis.2018.09.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 08/17/2018] [Accepted: 09/14/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND This study aimed to analyze the vascular wall and atherosclerotic plaques of the middle cerebral artery (MCA) and compare their differences between patients with cerebral infarction and transient ischemic attack (TIA) using 3-dimensional fast-spin-echo T1-weighted sequence (namely CUBE). METHODS Forty-seven patients with atherosclerotic stenosis of the MCA were included in this study. They received magnetic resonance examinations with routine T1WI, T2WI, 3-dimensional time-of-flight magnetic resonance angiography and diffusion-weighted imaging, as well as high-resolution CUBE T1WI sequence. Two physicians independently observed the location and degree of enhancement of the atheromatous plaques. The vessel area and lumen area at the maximal-lumen-narrowing and reference site were measured to calculate the plaque area, rate of stenosis, and remodeling index of the MCA. The chi-squared test was used to compare the differences of degree of enhancement between the cerebral infarction and TIA groups. The differences of rate of stenosis and remodeling index were compared by independent sample t test. RESULTS Twenty-five lesion vessels in the infarction group and 22 in the TIA group were analyzed. The difference of stenosis rate between the groups was not statistically significant. The lesion vessels of infarction group had a significantly larger remodeling index and plaque area, and the plaques had a significantly higher degree of enhancement, compared to the TIA group. CONCLUSIONS CUBE T1WI can be used to characterize the MCA vessel wall and atherosclerotic plaque. Positive remodeling and enhanced plaques are closely correlated with the occurrence of brain stroke.
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16
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Calcagno C, Fayad ZA. Imaging the Permeable Endothelium: Predicting Plaque Rupture in Atherosclerotic Rabbits. Circ Cardiovasc Imaging 2018; 9:CIRCIMAGING.116.005955. [PMID: 27940960 DOI: 10.1161/circimaging.116.005955] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Claudia Calcagno
- From the Translational and Molecular Imaging Institute (C.C., Z.A.F.) and Department of Radiology (C.C., Z.A.F.), Icahn School of Medicine at Mount Sinai, New York, NY
| | - Zahi A Fayad
- From the Translational and Molecular Imaging Institute (C.C., Z.A.F.) and Department of Radiology (C.C., Z.A.F.), Icahn School of Medicine at Mount Sinai, New York, NY.
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17
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Lavin B, Protti A, Lorrio S, Dong X, Phinikaridou A, Botnar RM, Shah A. MRI with gadofosveset: A potential marker for permeability in myocardial infarction. Atherosclerosis 2018; 275:400-408. [PMID: 29735362 PMCID: PMC6100880 DOI: 10.1016/j.atherosclerosis.2018.04.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2017] [Revised: 03/27/2018] [Accepted: 04/18/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIMS Acute ischemia is associated with myocardial endothelial damage and microvessel formation, resulting in leakage of plasma albumin into the myocardial extravascular space. In this study, we tested whether an albumin-binding intravascular contrast agent (gadofosveset) allows for improved quantification of myocardial permeability compared to the conventional extracellular contrast agent Gd-DTPA using late gadolinium enhancement (LGE) and T1 mapping in vivo. METHODS MI was induced in C57BL/6 mice (n = 6) and cardiac magnetic resonance imaging (CMR) was performed at 3, 10 and 21 days post-MI using Gd-DTPA and 24 h later using gadofosveset. Functional, LGE and T1 mapping protocols were performed 45 min post-injection of the contrast agent. RESULTS LGE images showed that both contrast agents provided similar measurements of infarct area at all time points following MI. Importantly, the myocardial R1 measurements after administration of gadofosveset were higher in the acute phase-day 3 (R1 [s-1] = 6.29 ± 0.29) compared to the maturation phase-days 10 and 21 (R1 [s-1] = 4.76 ± 0.30 and 4.48 ± 0.14), suggesting that the uptake of this agent could be used to stage myocardial remodeling. No differences in myocardial R1 were observed after administration of Gd-DTPA at different time points post-MI (R1 [s-1] = 3d: 3.77 ± 0.37; 10d: 2.74 ± 0.06; 21d: 3.35 ± 0.26). The MRI results were validated by ex vivo histology that showed albumin leakage in the myocardium in the acute phase and microvessel formation at later stages. CONCLUSIONS We demonstrate the merits of an albumin-binding contrast agent for monitoring changes in myocardial permeability between acute ischemia and chronic post-MI myocardial remodeling.
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Affiliation(s)
- Begoña Lavin
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK; The British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, United Kingdom.
| | - Andrea Protti
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK; The British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, United Kingdom; Cardiovascular Division, James Black Centre, King's College Hospital Denmark Hill London, London, SE5 9NU, United Kingdom
| | - Silvia Lorrio
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK; The British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, United Kingdom
| | - Xuebin Dong
- Cardiovascular Division, James Black Centre, King's College Hospital Denmark Hill London, London, SE5 9NU, United Kingdom
| | - Alkystis Phinikaridou
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK; The British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, United Kingdom
| | - René M Botnar
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK; The British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, United Kingdom; Pontificia Universidad Católica de Chile, Escuela de Ingeniería, Santiago, Chile
| | - Ajay Shah
- The British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, United Kingdom; Cardiovascular Division, James Black Centre, King's College Hospital Denmark Hill London, London, SE5 9NU, United Kingdom
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18
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Engel LC, Landmesser U, Gigengack K, Wurster T, Manes C, Girke G, Jaguszewski M, Skurk C, Leistner DM, Lauten A, Schuster A, Hamm B, Botnar RM, Makowski MR, Bigalke B. Novel Approach for In Vivo Detection of Vulnerable Coronary Plaques Using Molecular 3-T CMR Imaging With an Albumin-Binding Probe. JACC Cardiovasc Imaging 2018; 12:297-306. [PMID: 29361487 DOI: 10.1016/j.jcmg.2017.10.026] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/18/2017] [Accepted: 10/18/2017] [Indexed: 11/15/2022]
Abstract
OBJECTIVES This study sought to investigate the potential of the noninvasive albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR) for detection of coronary plaques that can cause acute coronary syndromes (ACS). BACKGROUND ACS are frequently caused by rupture or erosion of coronary plaques that initially do not cause hemodynamically significant stenosis and are therefore not detected by invasive x-ray coronary angiography (XCA). METHODS A total of 25 patients with ACS or symptoms of stable coronary artery disease underwent GE-CMR, clinically indicated XCA, and optical coherence tomography (OCT) within 24 h. GE-CMR was performed approximately 24 h following a 1-time application of gadofosveset-trisodium. Contrast-to-noise ratio (CNR) was quantified within coronary segments in comparison with blood signal. RESULTS A total of 207 coronary segments were analyzed on GE-CMR. Segments containing a culprit lesion in ACS patients (n = 11) showed significant higher signal enhancement (CNR) following gadofosveset-trisodium application than segments without culprit lesions (n = 196; 6.1 [3.9 to 16.5] vs. 2.1 [0.5 to 3.5]; p < 0.001). GE-CMR was able to correctly identify culprit coronary lesions in 9 of 11 segments (sensitivity 82%) and correctly excluded culprit coronary lesions in 162 of 195 segments (specificity 83%). Additionally, segmented areas of thin-cap fibroatheroma (n = 22) as seen on OCT demonstrated significantly higher CNR than segments without coronary plaque or segments containing early atherosclerotic lesions (n = 185; 9.2 [3.3 to 13.7] vs. 2.1 [0.5 to 3.4]; p = 0.001). CONCLUSIONS In this study, we demonstrated for the first time the noninvasive detection of culprit coronary lesions and thin-cap fibroatheroma of the coronary arteries in vivo by using GE-CMR. This method may represent a novel approach for noninvasive cardiovascular risk prediction.
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Affiliation(s)
- Leif-Christopher Engel
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany
| | - Ulf Landmesser
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany
| | - Kevin Gigengack
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Thomas Wurster
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Constantina Manes
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Georg Girke
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Milosz Jaguszewski
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Carsten Skurk
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - David M Leistner
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Alexander Lauten
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Schuster
- Department of Cardiology, Royal North Shore Hospital, The Kolling Institute, Northern Clinical School, University of Sydney, Sydney, Australia; Department of Cardiology and Pulmonology, German Centre for Cardiovascular Research Deutsches Zentrum für Herz-Kreislauf-Forschung e.V. (DZHK) Partner Site, Göttingen, Germany
| | - Bernd Hamm
- Klinik für Radiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Rene M Botnar
- Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom; Pontificia Universidad Católica de Chile Escuela de Ingeniería, Santiago, Chile
| | - Marcus R Makowski
- Klinik für Radiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany.
| | - Boris Bigalke
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany.
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Nahrendorf M, Vandoorne K. Albumin-Binding MR Probe Detects High-Risk Coronary Plaques in Patients. JACC Cardiovasc Imaging 2018; 12:307-309. [PMID: 29361477 DOI: 10.1016/j.jcmg.2017.11.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Accepted: 11/07/2017] [Indexed: 11/30/2022]
Affiliation(s)
- Matthias Nahrendorf
- Center for Systems Biology and Department of Imaging, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
| | - Katrien Vandoorne
- Center for Systems Biology and Department of Imaging, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
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20
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Lavin Plaza B, Gebhardt P, Phinikaridou A, Botnar RM. Atherosclerotic Plaque Imaging. PROTOCOLS AND METHODOLOGIES IN BASIC SCIENCE AND CLINICAL CARDIAC MRI 2018:261-300. [DOI: 10.1007/978-3-319-53001-7_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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21
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Leenders GJ, Smeets MB, van den Boomen M, Berben M, Nabben M, van Strijp D, Strijkers GJ, Prompers JJ, Arslan F, Nicolay K, Vandoorne K. Statins Promote Cardiac Infarct Healing by Modulating Endothelial Barrier Function Revealed by Contrast-Enhanced Magnetic Resonance Imaging. Arterioscler Thromb Vasc Biol 2017; 38:186-194. [PMID: 29146749 DOI: 10.1161/atvbaha.117.310339] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 10/24/2017] [Indexed: 01/13/2023]
Abstract
OBJECTIVE The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI). APPROACH AND RESULTS Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE-/-, and statin-treated ApoE-/- mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE-/- infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE-/- infarcts, indicated by reduced permeability. The infarcted tissue of ApoE-/- mice 3 days post-MI displayed an unbalanced Vegfa(vascular endothelial growth factor A)/Angpt1 (angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45+ leukocytes and inflammatory LY6Chi monocytes. Statins reversed the unbalanced Vegfa/Angpt1 expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE-/- mice. CONCLUSIONS Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.
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Affiliation(s)
- Geert J Leenders
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Mirjam B Smeets
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Maaike van den Boomen
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Monique Berben
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Miranda Nabben
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Dianne van Strijp
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Gustav J Strijkers
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Jeanine J Prompers
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Fatih Arslan
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Klaas Nicolay
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.)
| | - Katrien Vandoorne
- From the Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, The Netherlands (G.J.L., M.v.d.B., M.N., G.J.S., J.J.P., K.N., K.V.); Laboratory of Experimental Cardiology (M.B.S.) and Department of Cardiology (F.A.), University Medical Center Utrecht, The Netherlands; Department Precision and Decentralized Diagnostics, Philips Research Eindhoven, The Netherlands (M.B., D.v.S.); Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (G.J.S.); and Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands (F.A.).
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Coolen BF, Calcagno C, van Ooij P, Fayad ZA, Strijkers GJ, Nederveen AJ. Vessel wall characterization using quantitative MRI: what's in a number? MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE 2017; 31:201-222. [PMID: 28808823 PMCID: PMC5813061 DOI: 10.1007/s10334-017-0644-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 07/04/2017] [Accepted: 07/18/2017] [Indexed: 12/15/2022]
Abstract
The past decade has witnessed the rapid development of new MRI technology for vessel wall imaging. Today, with advances in MRI hardware and pulse sequences, quantitative MRI of the vessel wall represents a real alternative to conventional qualitative imaging, which is hindered by significant intra- and inter-observer variability. Quantitative MRI can measure several important morphological and functional characteristics of the vessel wall. This review provides a detailed introduction to novel quantitative MRI methods for measuring vessel wall dimensions, plaque composition and permeability, endothelial shear stress and wall stiffness. Together, these methods show the versatility of non-invasive quantitative MRI for probing vascular disease at several stages. These quantitative MRI biomarkers can play an important role in the context of both treatment response monitoring and risk prediction. Given the rapid developments in scan acceleration techniques and novel image reconstruction, we foresee the possibility of integrating the acquisition of multiple quantitative vessel wall parameters within a single scan session.
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Affiliation(s)
- Bram F Coolen
- Department of Biomedical Engineering and Physics, Academic Medical Center, PO BOX 22660, 1100 DD, Amsterdam, The Netherlands. .,Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands.
| | - Claudia Calcagno
- Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Pim van Ooij
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Zahi A Fayad
- Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Gustav J Strijkers
- Department of Biomedical Engineering and Physics, Academic Medical Center, PO BOX 22660, 1100 DD, Amsterdam, The Netherlands
| | - Aart J Nederveen
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
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Phinikaridou A, Andia ME, Lavin B, Smith A, Saha P, Botnar RM. Increased Vascular Permeability Measured With an Albumin-Binding Magnetic Resonance Contrast Agent Is a Surrogate Marker of Rupture-Prone Atherosclerotic Plaque. Circ Cardiovasc Imaging 2016; 9:e004910. [PMID: 27940955 PMCID: PMC5388187 DOI: 10.1161/circimaging.116.004910] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Accepted: 09/30/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Compromised structural integrity of the endothelium and higher microvessel density increase vascular permeability. We investigated whether vascular permeability measured in vivo by magnetic resonance imaging using the albumin-binding contrast agent, gadofosveset, is a surrogate marker of rupture-prone atherosclerotic plaque in a rabbit model. METHODS AND RESULTS New Zealand white rabbits (n=10) were rendered atherosclerotic by cholesterol-diet and endothelial denudation. Plaque rupture was triggered with Russell's viper venom and histamine. Animals were imaged pre-triggering, at 3 and 12 weeks, to quantify plaque area, vascular permeability, vasodilation, and stiffness and post-triggering to identify thrombus. Plaques identified on the pretrigger scans were classified as stable or rupture-prone based on the absence or presence of thrombus on the corresponding post-trigger magnetic resonance imaging, respectively. All rabbits had developed atherosclerosis, and 60% had ruptured plaques. Rupture-prone plaques had higher vessel wall relaxation rate (R1; 2.30±0.5 versus 1.86±0.3 s-1; P<0.001), measured 30 minutes after gadofosveset administration, and higher R1/plaque area ratio (0.70±0.06 versus 0.47±0.02, P= 0.01) compared with stable plaque at 12 weeks. Rupture-prone plaques had higher percent change in R1 between the 3 and 12 weeks compared with stable plaque (50.80±7.2% versus 14.22±2.2%; P<0.001). Immunohistochemistry revealed increased vessel wall albumin and microvessel density in diseased aortas and especially in ruptured plaque. Electron microscopy showed lack of structural integrity in both luminal and microvascular endothelium in diseased vessels. Functionally, the intrinsic vasodilation of the vessel wall decreased at 12 weeks compared with 3 weeks (18.60±1.0% versus 23.43±0.8%; P<0.001) and in rupture-prone compared with stable lesions (16.40±2.0% versus 21.63±1.2%; P<0.001). Arterial stiffness increased at 12 weeks compared with 3 weeks (5.00±0.1 versus 2.53±0.2 m/s; P<0.001) both in animals with stable and rupture-prone lesions. CONCLUSIONS T1 mapping using an albumin-binding contrast agent (gadofosveset) could quantify the changes in vascular permeability associated with atherosclerosis progression and rupture-prone plaques.
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Affiliation(s)
- Alkystis Phinikaridou
- From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., B.L., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (P.S., R.M.B.), King's College London, United Kingdom; and Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile (M.E.A.).
| | - Marcelo E Andia
- From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., B.L., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (P.S., R.M.B.), King's College London, United Kingdom; and Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile (M.E.A.)
| | - Begoña Lavin
- From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., B.L., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (P.S., R.M.B.), King's College London, United Kingdom; and Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile (M.E.A.)
| | - Alberto Smith
- From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., B.L., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (P.S., R.M.B.), King's College London, United Kingdom; and Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile (M.E.A.)
| | - Prakash Saha
- From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., B.L., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (P.S., R.M.B.), King's College London, United Kingdom; and Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile (M.E.A.)
| | - René M Botnar
- From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., B.L., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (P.S., R.M.B.), King's College London, United Kingdom; and Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile (M.E.A.)
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Pozo E, Agudo-Quilez P, Rojas-González A, Alvarado T, Olivera MJ, Jiménez-Borreguero LJ, Alfonso F. Noninvasive diagnosis of vulnerable coronary plaque. World J Cardiol 2016; 8:520-533. [PMID: 27721935 PMCID: PMC5039354 DOI: 10.4330/wjc.v8.i9.520] [Citation(s) in RCA: 7] [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: 04/29/2016] [Revised: 07/01/2016] [Accepted: 07/22/2016] [Indexed: 02/06/2023] Open
Abstract
Myocardial infarction and sudden cardiac death are frequently the first manifestation of coronary artery disease. For this reason, screening of asymptomatic coronary atherosclerosis has become an attractive field of research in cardiovascular medicine. Necropsy studies have described histopathological changes associated with the development of acute coronary events. In this regard, thin-cap fibroatheroma has been identified as the main vulnerable coronary plaque feature. Hence, many imaging techniques, such as coronary computed tomography, cardiac magnetic resonance or positron emission tomography, have tried to detect noninvasively these histomorphological characteristics with different approaches. In this article, we review the role of these diagnostic tools in the detection of vulnerable coronary plaque with particular interest in their advantages and limitations as well as the clinical implications of the derived findings.
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25
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Lavin B, Phinikaridou A, Lorrio S, Zaragoza C, Botnar RM. Monitoring vascular permeability and remodeling after endothelial injury in a murine model using a magnetic resonance albumin-binding contrast agent. Circ Cardiovasc Imaging 2015; 8:CIRCIMAGING.114.002417. [PMID: 25873720 PMCID: PMC4405074 DOI: 10.1161/circimaging.114.002417] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Despite the beneficial effects of vascular interventions, these procedures may damage the endothelium leading to increased vascular permeability and remodeling. Re-endothelialization of the vessel wall, with functionally and structurally intact cells, is controlled by endothelial nitric oxide synthase (NOS3) and is crucial for attenuating adverse effects after injury. We investigated the applicability of the albumin-binding MR contrast agent, gadofosveset, to noninvasively monitor focal changes in vascular permeability and remodeling, after injury, in NOS3-knockout (NOS3(-/-)) and wild-type (WT) mice in vivo. METHODS AND RESULTS WT and NOS3(-/-) mice were imaged at 7, 15, and 30 days after aortic denudation or sham-surgery. T1 mapping (R1=1/T1, s(-1)) and delayed-enhanced MRI were used as measurements of vascular permeability (R1) and remodeling (vessel wall enhancement, mm(2)) after gadofosveset injection, respectively. Denudation resulted in higher vascular permeability and vessel wall enhancement 7 days after injury in both strains compared with sham-operated animals. However, impaired re-endothelialization and increased neovascularization in NOS3(-/-) mice resulted in significantly higher R1 at 15 and 30 days post injury compared with WT mice that showed re-endothelialization and lack of neovascularization (R1 [s(-1)]=15 days: NOS3 (-/-)4.02 [interquartile range, IQR, 3.77-4.41] versus WT2.39 [IQR, 2.35-2.92]; 30 days: NOS3 (-/-)4.23 [IQR, 3.94-4.68] versus WT2.64 [IQR, 2.33-2.80]). Similarly, vessel wall enhancement was higher in NOS3(-/-) but recovered in WT mice (area [mm(2)]=15 days: NOS3 (-/-)5.20 [IQR, 4.68-6.80] versus WT2.13 [IQR, 0.97-3.31]; 30 days: NOS3 (-/-)7.35 [IQR, 5.66-8.61] versus WT1.60 [IQR, 1.40-3.18]). Ex vivo histological studies corroborated the MRI findings. CONCLUSIONS We demonstrate that increased vascular permeability and remodeling, after injury, can be assessed noninvasively using an albumin-binding MR contrast agent and may be used as surrogate markers for evaluating the healing response of the vessel wall after injury.
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Affiliation(s)
- Begoña Lavin
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom (B.L., A.P., S.L., R.M.B.); The British Heart Foundation Centre of Excellence, Cardiovascular Division (B.L., A.P., R.M.B.) and Wellcome Trust and EPSRC Medical Engineering Center (B.L., R.M.B.), King's College London, London, United Kingdom; Cardiovascular Research Unit, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, Madrid 28034, Spain (C.Z.).
| | - Alkystis Phinikaridou
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom (B.L., A.P., S.L., R.M.B.); The British Heart Foundation Centre of Excellence, Cardiovascular Division (B.L., A.P., R.M.B.) and Wellcome Trust and EPSRC Medical Engineering Center (B.L., R.M.B.), King's College London, London, United Kingdom; Cardiovascular Research Unit, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, Madrid 28034, Spain (C.Z.)
| | - Silvia Lorrio
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom (B.L., A.P., S.L., R.M.B.); The British Heart Foundation Centre of Excellence, Cardiovascular Division (B.L., A.P., R.M.B.) and Wellcome Trust and EPSRC Medical Engineering Center (B.L., R.M.B.), King's College London, London, United Kingdom; Cardiovascular Research Unit, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, Madrid 28034, Spain (C.Z.)
| | - Carlos Zaragoza
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom (B.L., A.P., S.L., R.M.B.); The British Heart Foundation Centre of Excellence, Cardiovascular Division (B.L., A.P., R.M.B.) and Wellcome Trust and EPSRC Medical Engineering Center (B.L., R.M.B.), King's College London, London, United Kingdom; Cardiovascular Research Unit, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, Madrid 28034, Spain (C.Z.)
| | - René M Botnar
- From the Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom (B.L., A.P., S.L., R.M.B.); The British Heart Foundation Centre of Excellence, Cardiovascular Division (B.L., A.P., R.M.B.) and Wellcome Trust and EPSRC Medical Engineering Center (B.L., R.M.B.), King's College London, London, United Kingdom; Cardiovascular Research Unit, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, Madrid 28034, Spain (C.Z.)
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Nörenberg D, Ebersberger HU, Diederichs G, Hamm B, Botnar RM, Makowski MR. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease. Eur Radiol 2015; 26:910-20. [DOI: 10.1007/s00330-015-3881-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 04/27/2015] [Accepted: 06/08/2015] [Indexed: 11/29/2022]
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27
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Lundeberg E, Van Der Does AM, Kenne E, Soehnlein O, Lindbom L. Assessing Large-Vessel Endothelial Permeability Using Near-Infrared Fluorescence Imaging—Brief Report. Arterioscler Thromb Vasc Biol 2015; 35:783-6. [DOI: 10.1161/atvbaha.114.305131] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective—
Loss of endothelial barrier function in arterial blood vessels is characteristic of vascular pathologies, including atherosclerosis. Here, we present a near-infrared fluorescence (NIRF) imaging methodology for quantifying endothelial permeability and macromolecular uptake in large arteries in the mouse and evaluate its applicability for studying mechanisms of vascular inflammation.
Approach and Results—
To validate the NIRF methodology, macrovascular inflammation was induced in C57bl/6 mice by local tumor necrosis factor-α stimulation of the carotid artery or in apolipoprotein E–deficient mice by Western diet for 4 weeks. Evans blue dye, serving as plasma protein marker and fluorescent in the near-infrared spectrum, was given intravenously at different doses. Carotids and aorta were excised, and Evans blue dye fluorescence was assessed through whole vessel scan in an infrared imaging system. NIRF correlated to extraction–absorbance methodology for Evans blue dye quantification and was superior at discriminating plasma protein accumulation in tumor necrosis factor-α–stimulated carotids. NIRF allowed for focal quantification of increased arterial wall Evans blue dye uptake in
apolipoprotein E–deficient
mice. Importantly, NIRF left vessels intact for subsequent histological analysis or quantification of leukocyte subpopulations by flow cytometry.
Conclusions—
The described NIRF methodology provides a sensitive and rapid tool to locate and quantify macromolecular uptake in the wall of arterial blood vessels in vascular pathologies in mice.
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Affiliation(s)
- Erik Lundeberg
- From the Department of Physiology and Pharmacology (E.L., A.M.V.D.D., E.K., L.L.) and Department of Molecular Medicine and Surgery, Center of Molecular Medicine (E.K.), Karolinska Institutet, Stockholm, Sweden; Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Munich, Germany (O.S.); Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (O.S.); and German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart
| | - Anne M. Van Der Does
- From the Department of Physiology and Pharmacology (E.L., A.M.V.D.D., E.K., L.L.) and Department of Molecular Medicine and Surgery, Center of Molecular Medicine (E.K.), Karolinska Institutet, Stockholm, Sweden; Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Munich, Germany (O.S.); Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (O.S.); and German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart
| | - Ellinor Kenne
- From the Department of Physiology and Pharmacology (E.L., A.M.V.D.D., E.K., L.L.) and Department of Molecular Medicine and Surgery, Center of Molecular Medicine (E.K.), Karolinska Institutet, Stockholm, Sweden; Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Munich, Germany (O.S.); Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (O.S.); and German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart
| | - Oliver Soehnlein
- From the Department of Physiology and Pharmacology (E.L., A.M.V.D.D., E.K., L.L.) and Department of Molecular Medicine and Surgery, Center of Molecular Medicine (E.K.), Karolinska Institutet, Stockholm, Sweden; Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Munich, Germany (O.S.); Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (O.S.); and German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart
| | - Lennart Lindbom
- From the Department of Physiology and Pharmacology (E.L., A.M.V.D.D., E.K., L.L.) and Department of Molecular Medicine and Surgery, Center of Molecular Medicine (E.K.), Karolinska Institutet, Stockholm, Sweden; Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Munich, Germany (O.S.); Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (O.S.); and German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart
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Abstract
This perspective outlines strategies towards the development of MR imaging probes that our lab has explored over the last 15 years. Namely, we discuss methods to enhance the signal generating capacity of MR probes and how to achieve tissue specificity through protein targeting or probe activation within the tissue microenvironment.
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Affiliation(s)
- Eszter Boros
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Eric M Gale
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
| | - Peter Caravan
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
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Lavin B, Phinikaridou A, Henningsson M, Botnar RM. Current Development of Molecular Coronary Plaque Imaging using Magnetic Resonance Imaging towards Clinical Application. CURRENT CARDIOVASCULAR IMAGING REPORTS 2014. [DOI: 10.1007/s12410-014-9309-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Amarteifio E, Essig M, Böckler D, Attigah N, Schuster L, Demirel S. Comparison of gadofosveset (Vasovist(®)) with gadobenate dimeglumine (Multihance(®))-enhanced MR angiography for high-grade carotid artery stenosis. J Neuroradiol 2014; 42:236-44. [PMID: 24996569 DOI: 10.1016/j.neurad.2014.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 03/16/2014] [Accepted: 03/19/2014] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To prove superiority of blood pool contrast agent gadofosveset over conventional contrast agent gadobenate dimeglumine for assessment of stenotic internal carotid artery (ICA). METHODS Eleven patients with high-grade ICA stenosis (≥75%), confirmed by duplex sonography, underwent MR angiography (MRA) with gadofosveset and gadobenate dimeglumine. RESULTS Agreement in stenosis grade was reached in 7 of 10 stenotic ICAs. In two ICAs, gadobenate dimeglumine led to underestimation of stenosis grade. There was a significant difference in signal intensity (pre-/post-stenotic segments), showing higher values for gadofosveset (P<0.01; P<0.05). Impression of contrast intensity with gadofosveset was better in 8 ICAs and only in 1 ICA with gadobenate dimeglumine (P<0.05). CONCLUSION Gadofosveset-enhanced MR angiography may be superior for assessment of high-grade ICA stenosis compared with gadobenate dimeglumine MR angiography.
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Affiliation(s)
- E Amarteifio
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany; Department of Radiology, German Cancer Research Center (dkfz), Heidelberg, Germany
| | - M Essig
- Department of Radiology, University of Manitoba, GA216-820 Sherbrook Street, MB R3T 2N2 Manitoba, Winnipeg, Canada
| | - D Böckler
- Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg, Germany
| | - N Attigah
- Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg, Germany
| | - L Schuster
- Department of Radiology, German Cancer Research Center (dkfz), Heidelberg, Germany
| | - S Demirel
- Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg, Germany.
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31
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Saba L, Anzidei M, Marincola BC, Piga M, Raz E, Bassareo PP, Napoli A, Mannelli L, Catalano C, Wintermark M. Imaging of the carotid artery vulnerable plaque. Cardiovasc Intervent Radiol 2014; 37:572-585. [PMID: 23912494 DOI: 10.1007/s00270-013-0711-2] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Accepted: 07/03/2013] [Indexed: 11/28/2022]
Abstract
Atherosclerosis involving the carotid arteries has a high prevalence in the population worldwide. This condition is significant because accidents of the carotid artery plaque are associated with the development of cerebrovascular events. For this reason, carotid atherosclerotic disease needs to be diagnosed and those determinants that are associated to an increased risk of stroke need to be identified. The degree of stenosis typically has been considered the parameter of choice to determine the therapeutical approach, but several recently published investigations have demonstrated that the degree of luminal stenosis is only an indirect indicator of the atherosclerotic process and that direct assessment of the plaque structure and composition may be key to predict the development of future cerebrovascular ischemic events. The concept of "vulnerable plaque" was born, referring to those plaque's parameters that concur to the instability of the plaque making it more prone to the rupture and distal embolization. The purpose of this review is to describe the imaging characteristics of "vulnerable carotid plaques."
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Affiliation(s)
- Luca Saba
- Department of Radiology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Polo di Monserrato, s.s. 554, 09045, Monserrato, Cagliari, Italy,
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32
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The Great Migration: How MRI Replaces Traditional Imaging Techniques for the Characterization of Atherosclerosis. CURRENT RADIOLOGY REPORTS 2014. [DOI: 10.1007/s40134-013-0040-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Makowski MR, Botnar RM. MR imaging of the arterial vessel wall: molecular imaging from bench to bedside. Radiology 2013; 269:34-51. [PMID: 24062561 DOI: 10.1148/radiol.13102336] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Cardiovascular diseases remain the leading cause of morbidity and mortality in the Western world and developing countries. In clinical practice, in vivo characterization of atherosclerotic lesions causing myocardial infarction, ischemic stroke, and other complications remains challenging. Imaging methods, limited to the assessment luminal stenosis, are the current reference standard for the assessment of clinically significant coronary and carotid artery disease and the guidance of treatment. These techniques do not allow distinction between stable and potentially vulnerable atherosclerotic plaque. Magnetic resonance (MR) imaging is a modality well suited for visualization and characterization of the relatively thin arterial vessel wall, because it allows imaging with high spatial resolution and excellent soft-tissue contrast. In clinical practice, atherosclerotic plaque components of the carotid artery and aorta may be differentiated and characterized by using unenhanced vessel wall MR imaging. Additional information can be gained by using clinically approved nonspecific contrast agents. With the advent of targeted MR contrast agents, which enhance specific molecules or cells, pathologic processes can be visualized at a molecular level with high spatial resolution. In this article, the pathophysiologic changes of the arterial vessel wall underlying the development of atherosclerosis will be first reviewed. Then basic principles and properties of molecular MR imaging contrast agents will be introduced. Additionally, recent advances in preclinical molecular vessel wall imaging will be reviewed. Finally, the clinical feasibility of arterial vessel wall imaging at unenhanced and contrast material-enhanced MR imaging of the aortic, carotid, and coronary vessel wall will be discussed.
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Affiliation(s)
- Marcus R Makowski
- Division of Imaging Sciences, BHF Centre of Excellence, Wellcome Trust and EPSRC Medical Engineering Center, and NIHR Biomedical Research Centre, King's College London, 4th Floor, Lambeth Wing, St Thomas Hospital, London SE1 7EH, England
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Phinikaridou A, Andia ME, Lacerda S, Lorrio S, Makowski MR, Botnar RM. Molecular MRI of atherosclerosis. Molecules 2013; 18:14042-69. [PMID: 24232739 PMCID: PMC6270261 DOI: 10.3390/molecules181114042] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Revised: 10/29/2013] [Accepted: 10/29/2013] [Indexed: 11/22/2022] Open
Abstract
Despite advances in prevention, risk assessment and treatment, coronary artery disease (CAD) remains the leading cause of morbidity and mortality in Western countries. The lion's share is due to acute coronary syndromes (ACS), which are predominantly triggered by plaque rupture or erosion and subsequent coronary thrombosis. As the majority of vulnerable plaques does not cause a significant stenosis, due to expansive remodeling, and are rather defined by their composition and biological activity, detection of vulnerable plaques with x-ray angiography has shown little success. Non-invasive vulnerable plaque detection by identifying biological features that have been associated with plaque progression, destabilization and rupture may therefore be more appropriate and may allow earlier detection, more aggressive treatment and monitoring of treatment response. MR molecular imaging with target specific molecular probes has shown great promise for the noninvasive in vivo visualization of biological processes at the molecular and cellular level in animals and humans. Compared to other imaging modalities; MRI can provide excellent spatial resolution; high soft tissue contrast and has the ability to simultaneously image anatomy; function as well as biological tissue composition and activity.
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Affiliation(s)
- Alkystis Phinikaridou
- Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK; E-Mails: (A.P.); (M.E.A.); (S.L.); (S.L.); (M.R.M.)
| | - Marcelo E. Andia
- Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK; E-Mails: (A.P.); (M.E.A.); (S.L.); (S.L.); (M.R.M.)
- Radiology Department, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago 8331150, Chile
| | - Sara Lacerda
- Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK; E-Mails: (A.P.); (M.E.A.); (S.L.); (S.L.); (M.R.M.)
| | - Silvia Lorrio
- Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK; E-Mails: (A.P.); (M.E.A.); (S.L.); (S.L.); (M.R.M.)
| | - Marcus R. Makowski
- Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK; E-Mails: (A.P.); (M.E.A.); (S.L.); (S.L.); (M.R.M.)
- Department of Radiology, Charite, Berlin 10117, Germany
| | - René M. Botnar
- Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor, Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK; E-Mails: (A.P.); (M.E.A.); (S.L.); (S.L.); (M.R.M.)
- Wellcome Trust and ESPRC Medical Engineering Center, King’s College London, London SE1 7EH, UK
- BHF Centre of Excellence, King’s College London, London SE1 7EH, UK
- NIHR Biomedical Research Centre, King’s College London, London SE1 7EH, UK
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Makowski MR, Henningsson M, Spuentrup E, Kim WY, Maintz D, Manning WJ, Botnar RM. Characterization of coronary atherosclerosis by magnetic resonance imaging. Circulation 2013; 128:1244-55. [PMID: 24019445 DOI: 10.1161/circulationaha.113.002681] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Marcus R Makowski
- Division of Imaging Sciences and Biomedical Engineering (M.R.M., M.H., R.M.B.), BHF Center of Research Excellence (M.R.M., M.H., R.M.B.), Wellcome Trust and EPSRC Medical Engineering Center (M.H., R.M.B.), and NIHR Biomedical Research Center (M.H., R.M.B.), King's College London, London, UK; Department of Radiology, Charité, Berlin, Germany (M.R.M.); Department of Radiology and Nuclear Medicine, Hospital Saarbrucken, Saarbrucken, Germany (E.S.); Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Denmark (W.Y.K.); Department of Radiology, University of Cologne, Cologne, Germany (D.M.); and Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (W.J.M.)
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Phinikaridou A, Andia ME, Passacquale G, Ferro A, Botnar RM. Noninvasive MRI monitoring of the effect of interventions on endothelial permeability in murine atherosclerosis using an albumin-binding contrast agent. J Am Heart Assoc 2013; 2:e000402. [PMID: 24072533 PMCID: PMC3835253 DOI: 10.1161/jaha.113.000402] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Background Endothelial dysfunction promotes atherosclerosis. We investigated whether in vivo magnetic resonance imaging (MRI) using an albumin‐binding contrast agent, gadofosveset, could monitor the efficacy of minocycline and ebselen in reducing endothelial permeability and atherosclerotic burden in the brachiocephalic artery of high‐fat diet (HFD)–fed ApoE−/− mice. Methods and Results ApoE−/− mice were scanned 12 weeks after commencement of either a normal diet (controls) or an HFD. HFD‐fed ApoE−/− mice were either untreated or treated with minocycline or ebselen for 12 weeks. Delayed‐enhancement MRI and T1 mapping of the brachiocephalic artery, 30 minutes after injection of gadofosveset, showed increased vessel wall enhancement and relaxation rate (R1, s−1) in untreated HFD‐fed ApoE−/− mice (R1=3.8±0.52 s−1) compared with controls (R1=2.15±0.34 s−1, P<0.001). Conversely, minocycline‐treated (R1=2.7±0.17 s−1, P<0.001) and ebselen‐treated (R1=2.7±0.23 s−1, P<0.001) ApoE−/− mice showed less vessel wall enhancement compared with untreated HFD‐fed ApoE−/− mice. Mass spectroscopy showed a lower gadolinium concentration in the brachiocephalic artery of treated (minocycline=28.5±3 μmol/L, ebselen=32.4±4 μmol/L) compared with untreated HFD‐fed ApoE−/− mice (191±4.8 μmol/L) (P<0.02). Both interventions resulted in a lower plaque burden as measured by delayed‐enhancement MRI (minocycline=0.14±0.02 mm2, ebselen=0.20±0.09 mm2, untreated=0.44±0.01 mm2; P<0.001) and histology (minocycline=0.13±0.05 mm2, ebselen=0.18±0.02 mm2, untreated=0.32±0.04 mm2; P<0.002). Endothelium cells displayed fewer structural changes and smaller gap junction width in treated compared with untreated animals as seen by electron microscopy (minocycline=42.3±8.4 nm, ebselen=56.5±17 nm, untreated=2400±39 nm; P<0.001). Tissue flow cytometry of the brachiocephalic artery showed lower monocyte/macrophage content in both ebselen‐ and minocycline‐treated mice (8.06±3.2% and 7.62±1.73%, respectively) compared with untreated animals (20.1±2.2%) (P=0.03), with significant attenuation of the proinflammatory Ly6Chigh subtype (untreated mice, 42.64±6.1% of total monocytes; ebselen, 14.07±9.5% of total monocytes; minocycline, 26.42±0.6% of total monocytes). Conclusions We demonstrate that contrast‐enhanced MRI with an albumin‐binding contrast agent can be used to noninvasively monitor the effect of interventions on endothelial permeability and plaque burden. Blood albumin leakage could be a surrogate marker for the in vivo evaluation of interventions that aim at restoring endothelial integrity.
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Affiliation(s)
- Alkystis Phinikaridou
- Division of Imaging Science and Biomedical Engineering, King's College London, London, United Kingdom
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Gadolinium-Based Contrast Agents for Vessel Wall Magnetic Resonance Imaging (MRI) of Atherosclerosis. CURRENT CARDIOVASCULAR IMAGING REPORTS 2012; 6:11-24. [PMID: 23539505 DOI: 10.1007/s12410-012-9177-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cardiovascular disease due to atherosclerosis is the number one killer in the Western world, and threatens to become the major cause of morbidity and mortality worldwide. It is therefore paramount to develop non-invasive methods for the detection of high-risk, asymptomatic individuals before the onset of clinical symptoms or events. In the recent past, great strides have been made in the understanding of the pathological mechanisms involved in the atherosclerotic cascade down to the molecular details. This has allowed the development of contrast agents that can aid in the in vivo characterization of these processes. Gadolinium chelates are among the contrast media most commonly used in MR imaging. Originally used for MR angiography for the detection and quantification of vascular stenosis, more recently they have been applied to improve characterization of atherosclerotic plaques. In this manuscript, we will briefly review gadolinium-chelates (Gd) based contrast agents for non-invasive MR imaging of atherosclerosis. We will first describe Gd-based non-targeted FDA approved agents, used routinely in clinical practice for the evaluation of neovascularization in other diseases. Secondly, we will describe non-specific and specific targeted contrast agents, which have great potential for dissecting specific biological processes in the atherosclerotic cascade. Lastly, we will briefly compare Gd-based agents to others commonly used in MRI and to other imaging modalities.
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Phinikaridou A, Andia ME, Shah AM, Botnar RM. Advances in molecular imaging of atherosclerosis and myocardial infarction: shedding new light on in vivo cardiovascular biology. Am J Physiol Heart Circ Physiol 2012; 303:H1397-410. [PMID: 23064836 DOI: 10.1152/ajpheart.00583.2012] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Molecular imaging of the cardiovascular system heavily relies on the development of new imaging probes and technologies to facilitate visualization of biological processes underlying or preceding disease. Molecular imaging is a highly active research discipline that has seen tremendous growth over the past decade. It has broadened our understanding of oncologic, neurologic, and cardiovascular diseases by providing new insights into the in vivo biology of disease progression and therapeutic interventions. As it allows for the longitudinal evaluation of biological processes, it is ideally suited for monitoring treatment response. In this review, we will concentrate on the major accomplishments and advances in the field of molecular imaging of atherosclerosis and myocardial infarction with a special focus on magnetic resonance imaging.
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Affiliation(s)
- Alkystis Phinikaridou
- Division of Imaging Science and Biomedical Engineering, King's College London, United Kingdom.
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Millon A, Boussel L, Brevet M, Mathevet JL, Canet-Soulas E, Mory C, Scoazec JY, Douek P. Clinical and histological significance of gadolinium enhancement in carotid atherosclerotic plaque. Stroke 2012; 43:3023-8. [PMID: 22923447 DOI: 10.1161/strokeaha.112.662692] [Citation(s) in RCA: 115] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND PURPOSE Although the ability of MRI to investigate carotid plaque composition is well established, the mechanism and the significance of plaque gadolinium (Gd) enhancement remain unknown. We evaluated clinical and histological significance of Gd enhancement of carotid plaque in patients undergoing endarterectomy for carotid stenosis. METHODS Sixty-nine patients scheduled for a carotid endarterectomy prospectively underwent a 3-T MRI. Carotid plaque enhancement was assessed on T1-weighted images performed before and 5 minutes after Gd injection. Enhancement was recorded according to its localization. Histological analysis was performed of the entire plaque and of the area with matched contrast enhancement on MR images. RESULTS Gd enhancement was observed in 59% patients. Three types of carotid plaques were identified depending on enhancement location (shoulder region, shoulder and fibrous cap, and central in the plaque). Fibrous cap rupture, intraplaque hemorrhage, and plaque Gd enhancement was significantly more frequent in symptomatic than in asymptomatic patients (P=0.043, P<0.0001, and P=0.034, respectively). After histological analysis, Gd enhancement was significantly associated with vulnerable plaque (American Heart Association VI, P=0.006), neovascularization (P<0.0001), macrophages (P=0.030), and loose fibrosis (P<0.0001). Prevalence of neovessels, macrophages, and loose fibrosis in the area of Gd enhancement was 97%, 87%, and 80%, respectively, and was different depending on the enhancement location in the plaque. Fibrous cap status and composition were different depending on the type of plaque. CONCLUSIONS Gd enhancement of carotid plaque is associated with vulnerable plaque phenotypes and related to an inflammatory process.
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Affiliation(s)
- Antoine Millon
- Department of Vascular Surgery, University Hospital of Lyon, Lyon University, Lyon, France.
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Phinikaridou A, Andia ME, Protti A, Indermuehle A, Shah A, Smith A, Warley A, Botnar RM. Noninvasive magnetic resonance imaging evaluation of endothelial permeability in murine atherosclerosis using an albumin-binding contrast agent. Circulation 2012; 126:707-19. [PMID: 22753191 DOI: 10.1161/circulationaha.112.092098] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Endothelial dysfunction promotes atherosclerosis and precedes acute cardiovascular events. We investigated whether in vivo magnetic resonance imaging with the use of an albumin-binding contrast agent, gadofosveset, could detect endothelial damage associated with atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. Furthermore, we tested whether magnetic resonance imaging could noninvasively assess endothelial function by measuring the endothelial-dependent vasodilation in response to acetylcholine. METHODS AND RESULTS ApoE(-/-) mice were imaged at 4, 8, and 12 weeks after commencement of a high-fat diet. Statin-treated ApoE(-/-) mice were scanned after 12 weeks of a high-fat diet. Wild-type mice were imaged before and 48 hours after injection of Russell's viper venom, an endothelial toxin. Delayed enhancement magnetic resonance imaging and T1 mapping of the brachiocephalic artery, 30 minutes after injection of gadofosveset, showed increased vessel wall enhancement and relaxation rate (R(1)) with progression of atherosclerosis in ApoE(-/-)(R(1) [s(-1)]: R(4 weeks) 2.42±0.35, R(8 weeks) 3.45±0.54, R(12 weeks) 3.83±0.52) and Russell's viper venom-injected wild-type mice (R(1)=4.57±0.86). Conversely, wild-type (R(1)=2.15±0.34) and statin-treated ApoE(-/-) (R(1)=3.0±0.65) mice showed less enhancement. Uptake of gadofosveset correlated with Evans blue staining, morphological changes of endothelial cells, and widening of the cell-cell junctions, suggesting that uptake occurs in regions of increased vascular permeability. Endothelial-dependent vasomotor responses showed vasoconstriction of the arteries of the ApoE(-/-) (-22.22±7.95%) and Russell's viper venom-injected (-10.37±17.60%) mice compared with wild-type mice (32.45±12.35%). Statin treatment improved endothelium morphology and function (-8.12±8.22%). CONCLUSIONS We demonstrate the noninvasive assessment of endothelial permeability and function with the use of an albumin-binding magnetic resonance contrast agent. Blood albumin leakage could be a surrogate marker for the in vivo evaluation of interventions that aim to restore the endothelium.
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Affiliation(s)
- Alkystis Phinikaridou
- King's College London, Division of Imaging Sciences and Biomedical Engineering, The Rayne Institute, 4th Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, United Kingdom.
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Kraff O, Bitz AK, Breyer T, Kruszona S, Maderwald S, Brote I, Gizewski ER, Ladd ME, Quick HH. A Transmit/Receive Radiofrequency Array for Imaging the Carotid Arteries at 7 Tesla. Invest Radiol 2011; 46:246-54. [DOI: 10.1097/rli.0b013e318206cee4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Pedersen SF, Thrysøe SA, Paaske WP, Thim T, Falk E, Ringgaard S, Kim WY. CMR assessment of endothelial damage and angiogenesis in porcine coronary arteries using gadofosveset. J Cardiovasc Magn Reson 2011; 13:10. [PMID: 21269470 PMCID: PMC3036628 DOI: 10.1186/1532-429x-13-10] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Accepted: 01/26/2011] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Endothelial damage and angiogenesis are essential for atherosclerotic plaque development and destabilization. We sought to examine whether contrast enhanced cardiovascular magnetic resonance (CMR) using gadofosveset could show endothelial damage and neovessel formation in balloon injured porcine coronary arteries. METHODS AND RESULTS Data were obtained from seven pigs that all underwent balloon injury of the left anterior descending coronary artery (LAD) to induce endothelial damage and angiogenesis. Between one - 12 days (average four) after balloon injury, in vivo and ex vivo T1-weighted coronary CMR was performed after intravenous injection of gadofosveset. Post contrast, CMR showed contrast enhancement of the coronary arteries with a selective and time-dependent average expansion of the injured LAD segment area of 45% (p = 0.04; CI95 = [15%-75%]), indicating local extravasation of gadofosveset. Vascular and perivascular extravasation of albumin (marker of endothelial leakiness) and gadofosveset was demonstrated with agreement between Evans blue staining and ex vivo CMR contrast enhancement (p = 0.026). Coronary MRI contrast enhancement and local microvessel density determined by microscopic examination correlated (ρ = 0.82, p < 0.001). CONCLUSION Contrast enhanced coronary CMR with gadofosveset can detect experimentally induced endothelial damage and angiogenesis in the porcine coronary artery wall.
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Affiliation(s)
- Steen F Pedersen
- Dept. of Cardiothoracic and Vascular Surgery T, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
- MR-center, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
| | - Samuel A Thrysøe
- MR-center, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
| | - William P Paaske
- Dept. of Cardiothoracic and Vascular Surgery T, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
| | - Troels Thim
- Dept. of Cardiology, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
| | - Erling Falk
- Dept. of Cardiology, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
| | - Steffen Ringgaard
- MR-center, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
| | - Won Y Kim
- Dept. of Cardiology, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
- MR-center, Aarhus University Hospital Skejby, Brendstrupsgaardsvej 100, 8200 Aarhus N, Denmark
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