Advancing understanding of human coronary artery disease requires new methods that can be used in patients for studying atherosclerotic plaque microstructure in relation to the molecular mechanisms that underlie its initiation, progression and clinical complications, including myocardial infarction and sudden cardiac death. Here we report a dual-modality intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo using a combination of optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging. By providing simultaneous molecular information in the context of the surrounding tissue microstructure, this new catheter could provide new opportunities for investigating coronary atherosclerosis and stent healing and for identifying high-risk biological and structural coronary arterial plaques in vivo.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Current Cardiovascular Imaging Reports Open Access 01 May 2023
Scientific Reports Open Access 27 April 2022
Journal of Nanobiotechnology Open Access 24 October 2021
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Lloyd-Jones, D. et al. Heart disease and stroke statistics–2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119, 480–486 (2009).
Yun, S.H. et al. Comprehensive volumetric optical microscopy in vivo. Nat. Med. 12, 1429–1433 (2006).
Huang, D. et al. Optical coherence tomography. Science 254, 1178–1181 (1991).
Choma, M., Sarunic, M., Yang, C. & Izatt, J. Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Opt. Express 11, 2183–2189 (2003).
Hausler, G. & Lindner, M.W. “Coherence Radar” and “Spectral Radar”—new tools for dermatological diagnosis. J. Biomed. Opt. 3, 21–31 (1998).
Fujimoto, J.G. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat. Biotechnol. 21, 1361–1367 (2003).
Tearney, G.J. et al. Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging. JACC Cardiovasc. Imaging 1, 752–761 (2008).
Takarada, S. et al. Advantage of next-generation frequency-domain optical coherence tomography compared with conventional time-domain system in the assessment of coronary lesion. Catheter. Cardiovasc. Interv. 75, 202–206 (2010).
Jaffer, F.A. et al. Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis. Circulation 118, 1802–1809 (2008).
McCarthy, J.R. et al. Multimodal nanoagents for the detection of intravascular thrombi. Bioconjug. Chem. 20, 1251–1255 (2009).
Ntziachristos, V., Bremer, C. & Weissleder, R. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur. Radiol. 13, 195–208 (2003).
Sanz, J. & Fayad, Z.A. Imaging of atherosclerotic cardiovascular disease. Nature 451, 953–957 (2008).
Jaffer, F.A., Libby, P. & Weissleder, R. Optical and multimodality molecular imaging: insights into atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29, 1017–1024 (2009).
Ryu, S.Y., Choi, H.Y., Na, J., Choi, E.S. & Lee, B.H. Combined system of optical coherence tomography and fluorescence spectroscopy based on double-cladding fiber. Opt. Lett. 33, 2347–2349 (2008).
Yabushita, H. et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation 106, 1640–1645 (2002).
Takano, M. et al. Evaluation by optical coherence tomography of neointimal coverage of sirolimus-eluting stent three months after implantation. Am. J. Cardiol. 99, 1033–1038 (2007).
Kume, T. et al. Assessment of coronary arterial thrombus by optical coherence tomography. Am. J. Cardiol. 97, 1713–1717 (2006).
Camenzind, E., Steg, P.G. & Wijns, W. Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. Circulation 115, 1440–1455 discussion 1455 (2007).
Holmes, D.R. Jr. et al. Stent thrombosis. J. Am. Coll. Cardiol. 56, 1357–1365 (2010).
Finn, A.V. et al. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler. Thromb. Vasc. Biol. 27, 1500–1510 (2007).
Guagliumi, G. & Sirbu, V. Optical coherence tomography: high resolution intravascular imaging to evaluate vascular healing after coronary stenting. Catheter. Cardiovasc. Interv. 72, 237–247 (2008).
Chen, J. et al. In vivo imaging of proteolytic activity in atherosclerosis. Circulation 105, 2766–2771 (2002).
Prati, F. et al. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur. Heart J. 31, 401–415 (2010).
Terashima, M. et al. Accuracy and reproducibility of stent-strut thickness determined by optical coherence tomography. J. Invasive Cardiol. 21, 602–605 (2009).
Gonzalo, N. et al. Reproducibility of quantitative optical coherence tomography for stent analysis. EuroIntervention 5, 224–232 (2009).
de Boer, O.J., van der Wal, A.C., Teeling, P. & Becker, A.E. Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization? Cardiovasc. Res. 41, 443–449 (1999).
We thank J. Gardecki for preparation of the cadaver coronary artery and CVPath for pathology of the stented artery. We also thank A. Rosenthal and G. Mallas for their technical support and A. Mauskapf for preparing and assisting in animal procedures. We thank Y. Iwamoto, Y. Yagi and E. Salomatina for assistance in histopathology. This research was supported in part by the US National Institutes of Health (R01HL076398 and R01HL093717 to G.J.T. and R01HL108229-01A1 to F.A.J.), the Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006 to G.J.T. and F.A.J.), an American Heart Association Scientist Development grant (#0830352N to F.A.J.), a Howard Hughes Medical Institute Early Career Award (F.A.J.) and the CardioVascular Research Foundation (CVRF, J.W.K.).
F.A.J. has received research support from Abbott Vascular, Boston Scientific and St. Jude's Medical. He has received honorarium from Boston Scientific. Terumo Corporation sponsors nonclinical optical frequency domain imaging research in the laboratories of G.J.T. and B.E.B. Massachusetts General Hospital has a licensing arrangement with Terumo Corporation, and G.J.T., M.S. and B.E.B. have the right to receive milestones and royalties from this licensing arrangement.
Supplementary Figures 1–8 and Supplementary Methods (PDF 6908 kb)
Simultaneous dual-modality imaging of a cadaveric coronary artery with an implanted NIR fluorescent-fibrin labeled stent, obtained ex vivo. The movie shows the OFDI cross-sectional images and the corresponding NIRF signals that are acquired during helical scan of the dual-modality catheter. (MOV 2268 kb)
Three-dimensional rendering of an OFDI-NIRF data set obtained from a rabbit iliac artery with an implanted NIR fluorescent-fibrin labeled stent in vivo. The following components of each of the OFDI images were segmented and rendered in color: artery wall (red); stent (white); thrombus (purple). The NIRF signal (flashing yellow) was overlaid on the luminal surface of the artery wall prior to volume rendering. (MOV 638 kb)
About this article
Cite this article
Yoo, H., Kim, J., Shishkov, M. et al. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat Med 17, 1680–1684 (2011). https://doi.org/10.1038/nm.2555
This article is cited by
Current Cardiovascular Imaging Reports (2023)
Scientific Reports (2022)
Nature Reviews Cardiology (2022)
Journal of Nanobiotechnology (2021)
Scientific Reports (2021)