Atherosclerotic Plaque Composition: Analysis with Multicolor CT and Targeted Gold Nanoparticles
Open accessAbstract
PURPOSE: To investigate the potential of spectral computed tomography (CT) (popularly referred to as multicolor CT), used in combination with a gold high-density lipoprotein nanoparticle contrast agent (Au-HDL), for characterization of macrophage burden, calcification, and stenosis of atherosclerotic plaques. MATERIALS AND METHODS: The local animal care committee approved all animal experiments. A preclinical spectral CT system in which incident x-rays are divided into six different energy bins was used for multicolor imaging. Au-HDL, an iodine-based contrast agent, and calcium phosphate were imaged in a variety of phantoms. Apolipoprotein E knockout (apo E-KO) mice were used as the model for atherosclerosis. Gold nanoparticles targeted to atherosclerosis (Au-HDL) were intravenously injected at a dose of 500 mg per kilogram of body weight. Iodine-based contrast material was injected 24 hours later, after which the mice were imaged. Wild-type mice were used as controls. Macrophage targeting by Au-HDL was further evaluated by using transmission electron microscopy and confocal microscopy of aorta sections. RESULTS: Multicolor CT enabled differentiation of Au-HDL, iodine-based contrast material, and calcium phosphate in the phantoms. Accumulations of Au-HDL were detected in the aortas of the apo E-KO mice, while the iodine-based contrast agent and the calcium-rich tissue could also be detected and thus facilitated visualization of the vasculature and bones (skeleton), respectively, during a single scanning examination. Microscopy revealed Au-HDL to be primarily localized in the macrophages on the aorta sections; hence, the multicolor CT images provided information about the macrophage burden. CONCLUSION: Spectral CT used with carefully chosen contrast agents may yield valuable information about atherosclerotic plaque composition.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Multicolour CT imaging allows identification of macrophage-rich atherosclerotic lesions in APOE-knockout mice.
“A gold-core version of the nanocrystal HDL platform mentioned above, which was previously shown — using MRI — to accumulate in plaques137, and an iodine-based blood-pool agent were injected simultaneously into APOE-knockout mice and clearly showed that multicolour CT imaging allows the identification of macrophage-rich atherosclerotic lesions142 (FIG. 6a).”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [142]
Cites
Markwell, M. A. K., Haas, S. M., BIEBER, L. L., & Tolbert, N. E. (1978) · Analytical Biochemistry · doi:10.1016/0003-2697(78)90586-9 · Cited by 6,460 · see citing works
Computerized transverse axial scanning (tomography): Part 1. Description of system
Hounsfield, G. N. (1973) · British Journal of Radiology · doi:10.1259/0007-1285-46-552-1016 · Cited by 3,930 · see citing works
Rouser, G., Fleischer, S., & Yamamoto, A. (1970) · Lipids · doi:10.1007/bf02531316 · Cited by 3,280 · see citing works
From Vulnerable Plaque to Vulnerable Patient
Naghavi, M., Libby, P., Falk, E., Casscells, S. W., Litovsky, S. H., Rumberger, J. A., Badimón, J. J., Stefanadis, C., Moreno, P., Pasterkamp, G., et al. (2003) · Circulation · doi:10.1161/01.cir.0000087481.55887.c9 · Cited by 2,686 · see citing works
Self-citationFrom Vulnerable Plaque to Vulnerable Patient
Naghavi, M., Libby, P., Falk, E., Casscells, S. W., Litovsky, S. H., Rumberger, J. A., Badimón, J. J., Stefanadis, C., Moreno, P., Pasterkamp, G., et al. (2003) · Circulation · doi:10.1161/01.cir.0000087480.94275.97 · Cited by 2,270 · see citing works
Self-citationBudoff, M. J., Dowe, D. A., Jollis, J. G., Gitter, M. J., Sutherland, J., Halamert, E., Scherer, M. D., Bellinger, R. L., Martin, A., Benton, R., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.07.031 · Cited by 2,121 · see citing works
Energy-selective reconstructions in X-ray computerised tomography
Alvarez, R. E., & Macovski, A. (1976) · Physics in Medicine and Biology · doi:10.1088/0031-9155/21/5/002 · Cited by 2,016 · see citing works
Davies, M. J., & Thomas, A. C. (1985) · Heart · doi:10.1136/hrt.53.4.363 · Cited by 1,985 · see citing works
Greenland, P. (2004) · JAMA · doi:10.1001/jama.291.2.210 · Cited by 1,825 · see citing works
ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.
Nakashima, Y., Plump, A. S., Raines, E. W., Breslow, J. L., & Ross, R. (1994) · Arteriosclerosis and Thrombosis: A Journal of Vascular Biology · doi:10.1161/01.atv.14.1.133 · Cited by 1,693 · see citing works
Assessment of Coronary Artery Disease by Cardiac Computed Tomography
Budoff, M. J., Achenbach, S. S., Blumenthal, R. S., Carr, J. J., Goldin, J. G., Greenland, P., Guerci, A. D., Lima, J. A. C., Rader, D. J., Rubin, G. D., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.178458 · Cited by 1,391 · see citing works
Weissleder, R., & Mahmood, U. (2001) · Radiology · doi:10.1148/radiology.219.2.r01ma19316 · Cited by 1,315 · see citing works
Quantification of Obstructive and Nonobstructive Coronary Lesions by 64-Slice Computed Tomography
Leber, A. W., Knez, A., von Ziegler, F., Becker, A., Nikolaou, K., Paul, S., Wintersperger, B. J., Reiser, M. F., Becker, C. R., Steinbeck, G., et al. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.03.071 · Cited by 1,100 · see citing works
Greenland, P., Bonow, R. O., Brundage, B. H., Budoff, M. J., Eisenberg, M. J., Grundy, S. M., Lauer, M. S., Post, W. S., Raggi, P., Redberg, R. F., et al. (2007) · Circulation · doi:10.1161/circulationaha..107.181425 · Cited by 931 · see citing works
Schlomka, J., Roessl, E., Dorscheid, R., Dill, S., Martens, G., Istel, T., Bäumer, C., Herrmann, C., Steadman, R., Zeitler, G., et al. (2008) · Physics in Medicine and Biology · doi:10.1088/0031-9155/53/15/002 · Cited by 803 · see citing works
Self-citationTargeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer
Popovtzer, R., Agrawal, A., Kotov, N. A., Popovtzer, A., Balter, J. M., Carey, T. E., & Kopelman, R. (2008) · Nano Letters · doi:10.1021/nl8029114 · Cited by 801 · see citing works
Ruehm, S. G., Corot, C., VOGT, P. R., Kolb, S., & Debatin, J. F. (2001) · Circulation · doi:10.1161/01.cir.103.3.415 · Cited by 600 · see citing works
K-edge imaging in x-ray computed tomography using multi-bin photon counting detectors
Roessl, E., & Proksa, R. (2007) · Physics in Medicine and Biology · doi:10.1088/0031-9155/52/15/020 · Cited by 561 · see citing works
Self-citationImaging of atherosclerotic cardiovascular disease
Sanz, J., & Fayad, Z. A. (2008) · Nature · doi:10.1038/nature06803 · Cited by 558 · see citing works
Self-citationEarls, J. P., Berman, E., Urban, B. A., Curry, C. A., Lane, J. L., Jennings, R. S., McCulloch, C. C., Hsieh, J., & Londt, J. H. (2008) · Radiology · doi:10.1148/radiol.2463070989 · Cited by 543 · see citing works
Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography
Hyafil, F., Cornily, J.-C., Feig, J. E., Gordon, R., Vucic, E., Amirbekian, V., Fisher, E. A., Fuster, V., Feldman, L. J., & Fayad, Z. A. (2007) · Nature Medicine · doi:10.1038/nm1571 · Cited by 467 · see citing works
Self-citationMetal-Based X-ray Contrast Media
Yu, S., & Watson, A. D. (1999) · Chemical Reviews · doi:10.1021/cr980441p · Cited by 433 · see citing works
Biomarkers of Atherosclerotic Plaque Instability and Rupture
Köenig, W., & Khuseyinova, N. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000251503.35795.4f · Cited by 417 · see citing works
Falk, E. (1992) · PubMed · Cited by 387 · see citing works
Nanocrystal Core High-Density Lipoproteins: A Multimodality Contrast Agent Platform
Cormode, D. P., Skajaa, T., van Schooneveld, M. M., Koole, R., Jarzyna, P., Lobatto, M. E., Calcagno, C., Barazza, A., Gordon, R. E., Zanzonico, P., et al. (2008) · Nano Letters · doi:10.1021/nl801958b · Cited by 328 · see citing works
Self-citation[32] Reconstitution of high-density lipoproteins
Jonas, A. (1986) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(86)28092-1 · Cited by 328 · see citing works
[26] Electron microscopy of negatively stained lipoproteins
Forte, T. M., & Nordhausen, R. W. (1986) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(86)28086-6 · Cited by 233 · see citing works
Feuerlein, S., Roessl, E., Proksa, R., et al. (2008) · Radiology · doi:10.1148/radiol.2492080560 · Cited by 195 · see citing works
Self-citationJaffer, F. A., & Weissleder, R. (2004) · Circulation Research · doi:10.1161/01.res.0000119321.18573.5a · Cited by 193 · see citing works
Iron Oxide Particles for Atheroma Imaging
Tang, T. Y., Müller, K. H., Graves, M. J., Li, Z. Y., Walsh, S. R., Young, V. E. L., Sadat, U., Howarth, S. P. S., & Gillard, J. H. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.165514 · Cited by 137 · see citing works
d -Mannose-Modified Iron Oxide Nanoparticles for Stem Cell Labeling
Horák, D., Babič, M., Jendelová, P., Herynek, V., Trchová, M., Pientka, Z., Pollert, E., Hájek, M., & Syková, E. (2007) · Bioconjugate Chemistry · doi:10.1021/bc060186c · Cited by 135 · see citing works
Cormode, D. P., Briley-Saebo, K. C., Mulder, W. J. M., Aguinaldo, J. G. S., Barazza, A., Ma, Y., Fisher, E. A. A., & Fayad, Z. A. (2008) · Small · doi:10.1002/smll.200701285 · Cited by 107 · see citing works
Self-citationCardiovascular molecular imaging: an overview
Saraste, A., Nekolla, S. G., & Schwaiger, M. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp209 · Cited by 88 · see citing works
Cormode, D. P., Chandrasekar, R., Delshad, A., Briley-Saebo, K. C., Calcagno, C., Barazza, A., Mulder, W. J. M., Fisher, E. A., & Fayad, Z. A. (2009) · Bioconjugate Chemistry · doi:10.1021/bc800520d · Cited by 72 · see citing works
Self-citationApplications of cardiac multidetector CT beyond coronary angiography
Schuleri, K. H., George, R. T., & Lardo, A. C. (2009) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2009.172 · Cited by 69 · see citing works
Boll, D. T., Patil, N. A., Paulson, E. K., et al. (2009) · Radiology · doi:10.1148/radiol.09090068 · Cited by 66 · see citing works
Ultrashort dead time of photon-counting InGaAs avalanche photodiodes
Dixon, A., Dynes, J., Yuan, Z., Sharpe, A., Bennett, A., Shields, A., et al. (2009) · Cambridge University Engineering Department Publications Database · Cited by 63 · see citing works
Molecular Imaging of Human Thrombus with Computed Tomography
Winter, P. M., Shukla, H. P., Caruthers, S. D., et al. (2005) · Academic Radiology · doi:10.1016/j.acra.2005.02.016 · Cited by 57 · see citing works
Ultrashort dead time of photon-counting InGaAs avalanche photodiodes
Dixon, A. R., Dynes, J. F., Yuan, Z. L., Sharpe, A. W., Bennett, A. J., & Shields, A. J. (2009) · Applied Physics Letters · doi:10.1063/1.3151864 · Cited by 49 · see citing works
X‐ray attenuation properties of radiographic contrast media
Lumbroso, P., & Dick, C. E. (1987) · Medical Physics · doi:10.1118/1.595999 · Cited by 22 · see citing works
Large area photon counting X-ray imaging arrays for clinical dual-energy applications
Barber, W. C., Nygärd, E., Wessel, J. C., et al. (2009) · 2006 IEEE Nuclear Science Symposium Conference Record · doi:10.1109/nssmic.2009.5401581 · Cited by 19 · see citing works
Wisner, E. R., Weichert, J. P., Longino, M. A., et al. (2002) · Investigative Radiology · doi:10.1097/00004424-200204000-00009 · Cited by 15 · see citing works
Coronary Computed Tomography Angiography
Rumberger, J. A. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.08.034 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Imaging macrophages with nanoparticles
Weissleder, R., Nahrendorf, M., & Pittet, M. J. (2014) · Nature Materials · doi:10.1038/nmat3780 · Cited by 809 · see citing works
Perspectives and opportunities for nanomedicine in the management of atherosclerosis
Lobatto, M. E., Fuster, V., Fayad, Z. A., & Mulder, W. J. M. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3578 · Cited by 423 · see citing works
Self-citationLeuschner, F., & Nahrendorf, M. (2011) · Circulation Research · doi:10.1161/circresaha.110.232678 · Cited by 110 · see citing works
HANDSCHUH, S., BEISSER, C. J., RUTHENSTEINER, B., & METSCHER, B. D. (2017) · Journal of Microscopy · doi:10.1111/jmi.12543 · Cited by 48 · see citing works
Standardization of Models and Methods Used to Assess Nanoparticles in Cardiovascular Applications
Fitzgerald, K. T., Holladay, C. A., McCarthy, C., Power, K. A., Pandit, A., & Gallagher, W. M. (2011) · Small · doi:10.1002/smll.201001347 · Cited by 26 · see citing works
- Authors
- Cormode, D. P., Roessl, E., Thran, A., Skajaa, T., Gordon, R. E., Schlomka, J.-P., Fuster, V., Fisher, E. A., Mulder, W. J. M., Proksa, R., & Fayad, Z. A.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Philips (Germany) (DE)
- Mount Sinai Hospital (US)
- New York University (US)
- Venue
- Radiology
- Published
- 2010-09
- Volume
- 256
- Issue
- 3
- Pages
- 774-782
- ISSN
- 0033-8419 (ISSN-L)
- 1527-1315
- PMC
- PMC2923725
- OpenAlex
- W2105050495
- Cited by
- 479
- References
- 43
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 21 · 2023: 34 · 2022: 27 · 2021: 37 · 2020: 41 · 2019: 31 · 2018: 36 · 2017: 37 · 2016: 28 · 2015: 30 · 2014: 40 · 2013: 34 · 2012: 33
- FWCI
- 17.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Radiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL061814, R01 HL 71021, R01HL078667, R01HL071021, R01 HL61814, R01 HL 78667)
- National Institute of Biomedical Imaging and Bioengineering (R01EB009638, K99EB012165)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Advanced X-ray and CT Imaging
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- atherosclerotic plaque composition, spectral computed tomography, gold nanoparticles, plaque calcification, iodinated contrast media, calcium phosphate, ApoE-deficient mice, atherosclerosis imaging
- MeSH terms
- Animals, Aortic Diseases, Color, Contrast Media, Gold, Iodine, Microscopy, Electron, Tomography, X-Ray Computed, Mice, Knockout, Microscopy, Confocal, Phantoms, Imaging, Atherosclerosis, Mice, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
