Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging
Open accessAbstract
BACKGROUND: One of the features of high-risk atherosclerotic plaques is a preponderance of macrophages. Experimental studies with hyperlipidemic rabbits have shown that ultrasmall superparamagnetic particles of iron oxide (USPIOs) accumulate in plaques with a high macrophage content and that this induces magnetic resonance (MR) signal changes. The purpose of our study was to investigate whether USPIO-enhanced MRI can also be used for in vivo detection of macrophages in human plaques. METHODS AND RESULTS: MRI was performed on 11 symptomatic patients scheduled for carotid endarterectomy before and 24 (n=11) and 72 (n=5) hours after administration of USPIOs (Sinerem) at a dose of 2.6 mg Fe/kg. Histological and electron microscopical analyses of the plaques showed USPIOs primarily in macrophages within the plaques in 10 of 11 patients. Histological analysis showed USPIOs in 27 of 36 (75%) of the ruptured and rupture-prone lesions and 1 of 14 (7%) of the stable lesions. Of the patients with USPIO uptake, signal changes in the post-USPIO MRI were observed by 2 observers in the vessel wall in 67 of 123 (54%) and 19 of 55 (35%) quadrants of the T2*-weighted MR images acquired after 24 and 72 hours, respectively. For those quadrants with changes, there was a significant signal decrease of 24% (95% CI, 33% to 15%) in regions of interest in the images acquired after 24 hours, whereas no significant signal change was found after 72 hours. CONCLUSIONS: Accumulation of USPIOs in macrophages in predominantly ruptured and rupture-prone human atherosclerotic lesions caused signal decreases in the in vivo MR images.
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USPIO/SPION uptake is increased in vulnerable or ruptured atherosclerotic plaques in rabbits and humans.
“Several groups have shown an increase in USPIO/ SPION uptake in vulnerable or ruptured atherosclerotic plaques in rabbits [171] and humans [172, 173] (Figure 4 A).”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [172]
In the first clinical study of USPIOs, 11 patients had a 24% decrease in signal intensity in their carotid arteries after USPIO injection.
“In the first clinical study of USPIOs, 11 patients who were scheduled for carotid endarterectomy before and after the injection of USPIOs had a 24% decrease in signal intensity in their carotid arteries after USPIO injection128.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [128]
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- Authors
- Kooi, M. E., Cappendijk, V. C., Cleutjens, K. B. J. M., Kessels, A. G. H., Kitslaar, P. J. E. H. M., Borgers, M., Frederik, P. M., Daemen, M. J. A. P., & van Engelshoven, J. M. A.
- Affiliations
- Maastricht University Medical Centre (NL)
- From the Cardiovascular Research Institute Maastricht (CARIM), Departments of Radiology (M.E.K., V.C.C., J.M.A.v.E.), Pathology (K.B.J.M.C., P.M.F., M.J.A.P.D.), Clinical Epidemiology and Medical Technology Assessment (A.G.H.K.), Surgery (P.J.E.H.M.K.), and Genetics and Cell Biology (M.B.), University Hospital Maastricht/University of Maastricht, the Netherlands.
- Venue
- Circulation
- Published
- 2003-05-20
- Volume
- 107
- Issue
- 19
- Pages
- 2453-2458
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2129445703
- Cited by
- 798
- References
- 14
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 17 · 2022: 16 · 2021: 26 · 2020: 22 · 2019: 30 · 2018: 21 · 2017: 41 · 2016: 23 · 2015: 52 · 2014: 41 · 2013: 32 · 2012: 48
- FWCI
- 33.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- TU/e Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Keywords
- ultrasmall superparamagnetic iron oxide, USPIO-enhanced MRI, atherosclerotic plaque, macrophages, plaque rupture, carotid endarterectomy, T2-weighted imaging, plaque imaging
- MeSH terms
- Carotid Arteries, Carotid Artery Diseases, Ischemic Attack, Transient, Dextrans, Electron Spin Resonance Spectroscopy, Endothelium, Vascular, Feasibility Studies, Female, Ferric Compounds, Humans, Iron, Macrophages, Magnetic Resonance Imaging, Male, Microscopy, Electron, Middle Aged, Muscle, Smooth, Vascular, Oxides, Particle Size, Predictive Value of Tests, Ferrosoferric Oxide, Magnetite Nanoparticles
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