High-Resolution Magnetic Resonance Imaging Enhanced With Superparamagnetic Nanoparticles Measures Macrophage Burden in Atherosclerosis
Open accessAbstract
Background—: Macrophages contribute to the progression and acute complications of atherosclerosis. Macrophage imaging may serve as a biomarker to identify subclinical inflamed lesions, to predict future risk, and to aid in the assessment of novel therapies. Methods and Results—: To test the hypothesis that nanoparticle-enhanced, high-resolution magnetic resonance imaging (MRI) can measure plaque macrophage accumulation, we used 3-T MRI with a macrophage-targeted superparamagnetic nanoparticle preparation (monocrystalline iron oxide nanoparticles-47 [MION-47]) in cholesterol-fed New Zealand White rabbits 6 months after balloon injury. In vivo MRI visualized thickened abdominal aortas on both T1- and T2-weighted spin-echo images (T1 spin echo, 20 axial slices per animal; T2 spin echo, 28 slices per animal). Seventy-two hours after MION-47 injection, aortas exhibited lower T2 signal intensity compared with before contrast imaging (signal intensity ratio, aortic wall/muscle: before, 1.44±0.26 versus after, 0.95±0.22; 164 slices; P <0.01), whereas T1 spin echo images showed no significant change. MRI on ex vivo specimens provided similar results. Histological studies colocalized iron accumulation with immunoreactive macrophages in atheromata. The magnitude of signal intensity reduction on T2 spin echo in vivo images further correlated with macrophage areas in situ (150 slices; r =0.73). Treatment with rosuvastatin for 3 months yielded diminished macrophage content ( P <0.05) and reversed T2 signal intensity changes ( P <0.005). Signal changes in rosuvastatin-treated rabbits correlated with reduced macrophage burden ( r =0.73). In vitro validation studies showed concentration-dependent MION-47 uptake by human primary macrophages. Conclusion—: The magnitude of T2 signal intensity reduction in high-resolution MRI after administration of superparamagnetic phagocytosable nanoparticles can assess macrophage burden in atheromata, providing a clinically translatable tool to identify inflamed plaques and to monitor therapy-mediated changes in plaque inflammation.
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SPIO facilitate internalization of nanoparticles in macrophages, as evidenced by incorporation of monocrystalline iron oxide particles in atherosclerotic macrophages.
“Furthermore, superparamagnetic iron oxide nanoparticles (SPIO) facilitate the internalization of nanoparticles in macrophages, as evidenced by the incorporation of monocrystalline iron oxide particles in atherosclerotic macrophages.153”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [153]
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- Authors
- Morishige, K., Kacher, D. F., Libby, P., Josephson, L., Ganz, P., Weissleder, R., & Aikawa, M.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Circulation
- Published
- 2010-10-26
- Volume
- 122
- Issue
- 17
- Pages
- 1707-1715
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC3003265
- OpenAlex
- W2004937569
- Cited by
- 168
- References
- 50
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 11 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 12 · 2015: 16 · 2014: 16 · 2013: 14 · 2012: 26
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- AstraZeneca
- Uehara Memorial Foundation
- Japan Heart Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-80472, U01HL080731, HL 66086, R01HL078641, HL-078641, HL 56895, R29HL056895, R01HL080472, R01HL066086, R01HL056895)
- National Center for Research Resources (U41RR019703, U41 RR19703)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- atherosclerosis, superparamagnetic iron oxide nanoparticles, plaque inflammation, T2 signal intensity, high-resolution MRI, rosuvastatin, balloon injury, rabbit model, phagocytosis, iron accumulation
- MeSH terms
- Rosuvastatin Calcium, Animals, Aorta, Abdominal, Cholesterol, Dietary, Disease Models, Animal, Fluorobenzenes, Macrophages, Magnetic Resonance Imaging, Male, Pyrimidines, Rabbits, Sulfonamides, Treatment Outcome, Disease Progression, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atherosclerosis, Ferrosoferric Oxide, Nanoparticles, Metal Nanoparticles
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