Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo


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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic of the dual-modality intra-arterial catheter for simultaneous microstructural and molecular imaging using OFDI and NIRF.
Figure 2: Images of a cadaveric human coronary artery with a stent containing Cy7-labeled fibrin in vitro.
Figure 3: Dual-modality OFDI-NIRF images of an iliac artery of a rabbit with an implanted NIR-fluorescent fibrin-coated stent, attained in vivo.
Figure 4: Dual-modality OFDI-NIRF images of atherosclerosis microstructure and inflammatory enzyme activity in a living rabbit.


  1. 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).

    Article  Google Scholar 

  2. Yun, S.H. et al. Comprehensive volumetric optical microscopy in vivo. Nat. Med. 12, 1429–1433 (2006).

    Article  CAS  Google Scholar 

  3. Huang, D. et al. Optical coherence tomography. Science 254, 1178–1181 (1991).

    Article  CAS  Google Scholar 

  4. 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).

    Article  Google Scholar 

  5. Hausler, G. & Lindner, M.W. “Coherence Radar” and “Spectral Radar”—new tools for dermatological diagnosis. J. Biomed. Opt. 3, 21–31 (1998).

    Article  CAS  Google Scholar 

  6. Fujimoto, J.G. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat. Biotechnol. 21, 1361–1367 (2003).

    Article  CAS  Google Scholar 

  7. Tearney, G.J. et al. Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging. JACC Cardiovasc. Imaging 1, 752–761 (2008).

    Article  Google Scholar 

  8. 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).

    Article  Google Scholar 

  9. Jaffer, F.A. et al. Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis. Circulation 118, 1802–1809 (2008).

    Article  Google Scholar 

  10. McCarthy, J.R. et al. Multimodal nanoagents for the detection of intravascular thrombi. Bioconjug. Chem. 20, 1251–1255 (2009).

    Article  CAS  Google Scholar 

  11. 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).

    Google Scholar 

  12. Sanz, J. & Fayad, Z.A. Imaging of atherosclerotic cardiovascular disease. Nature 451, 953–957 (2008).

    Article  CAS  Google Scholar 

  13. Jaffer, F.A., Libby, P. & Weissleder, R. Optical and multimodality molecular imaging: insights into atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29, 1017–1024 (2009).

    Article  CAS  Google Scholar 

  14. 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).

    Article  Google Scholar 

  15. Yabushita, H. et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation 106, 1640–1645 (2002).

    Article  Google Scholar 

  16. 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).

    Article  CAS  Google Scholar 

  17. Kume, T. et al. Assessment of coronary arterial thrombus by optical coherence tomography. Am. J. Cardiol. 97, 1713–1717 (2006).

    Article  Google Scholar 

  18. 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).

    Article  Google Scholar 

  19. Holmes, D.R. Jr. et al. Stent thrombosis. J. Am. Coll. Cardiol. 56, 1357–1365 (2010).

    Article  Google Scholar 

  20. Finn, A.V. et al. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler. Thromb. Vasc. Biol. 27, 1500–1510 (2007).

    Article  CAS  Google Scholar 

  21. 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).

    Article  Google Scholar 

  22. Chen, J. et al. In vivo imaging of proteolytic activity in atherosclerosis. Circulation 105, 2766–2771 (2002).

    Article  Google Scholar 

  23. 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).

    Article  Google Scholar 

  24. Terashima, M. et al. Accuracy and reproducibility of stent-strut thickness determined by optical coherence tomography. J. Invasive Cardiol. 21, 602–605 (2009).

    PubMed  Google Scholar 

  25. Gonzalo, N. et al. Reproducibility of quantitative optical coherence tomography for stent analysis. EuroIntervention 5, 224–232 (2009).

    Article  Google Scholar 

  26. 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).

    Article  CAS  Google Scholar 

Download references


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.).

Author information

Authors and Affiliations



H.Y. developed the dual-modality system and catheter and wrote the manuscript. H.Y. and J.W.K. designed and performed the experiments. H.Y., J.W.K., F.A.J. and G.J.T. analyzed and processed the data. M.S. contributed to catheter development. E.N. contributed to OFDI technology development. T.M. and R.S. designed and manufactured the double-clad fiber. J.R.M. synthesized the fibrin-targeted nanoagents. V.N. contributed to the design of experiments and development of the animal model protocols. B.E.B. contributed to OFDI technology development. F.A.J. and G.J.T. contributed to the design of experiments, preparation of the manuscript and supervised the overall project. All authors read and edited the manuscript.

Corresponding authors

Correspondence to Farouc A Jaffer or Guillermo J Tearney.

Ethics declarations

Competing interests

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 information

Supplementary Text and Figures

Supplementary Figures 1–8 and Supplementary Methods (PDF 6908 kb)

Supplementary Video 1

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)

Supplementary Video 2

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)

Rights and permissions

Reprints and Permissions

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing