Technical Report | Published:

Imaging the subcellular structure of human coronary atherosclerosis using micro–optical coherence tomography

Nature Medicine volume 17, pages 10101014 (2011) | Download Citation

Abstract

Progress in understanding, diagnosis, and treatment of coronary artery disease (CAD) has been hindered by our inability to observe cells and extracellular components associated with human coronary atherosclerosis in situ. The current standards for microstructural investigation, histology and electron microscopy are destructive and prone to artifacts. The highest-resolution intracoronary imaging modality, optical coherence tomography (OCT), has a resolution of 10 μm, which is too coarse for visualizing most cells. Here we report a new form of OCT, termed micro–optical coherence tomography (μOCT), whose resolution is improved by an order of magnitude. We show that μOCT images of cadaver coronary arteries provide clear pictures of cellular and subcellular features associated with atherogenesis, thrombosis and responses to interventional therapy. These results suggest that μOCT can complement existing diagnostic techniques for investigating atherosclerotic specimens, and that μOCT may eventually become a useful tool for cellular and subcellular characterization of the human coronary wall in vivo.

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References

  1. 1.

    , , , & Lessons from sudden coronary death—a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).

  2. 2.

    et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 92, 1355–1374 (1995).

  3. 3.

    , & Coronary atherosclerosis: determinants of plaque rupture. Eur. Heart J. 19, C24–C29 (1998).

  4. 4.

    Acute coronary thrombosis—The role of plaque disruption and its initiation and prevention. Eur. Heart J. 16, 3–7 (1995).

  5. 5.

    , , & Scanning electron microscopy after coronary transluminal angioplasty of normal canine coronary arteries. Am. J. Cardiol. 45, 591–598 (1980).

  6. 6.

    , , & Scanning electron microscopy of surface irregularities and thrombogenesis of polyurethane and polyethylene coronary catheters. Circulation 53, 992–996 (1976).

  7. 7.

    & Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events–a novel insight into plaque rupture by scanning electron microscopy. Scanning 28, 1–10 (2006).

  8. 8.

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

  9. 9.

    et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J. Am. Coll. Cardiol. 39, 604–609 (2002).

  10. 10.

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

  11. 11.

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

  12. 12.

    et al. In vivo cellular optical coherence tomography imaging. Nat. Med. 4, 861–865 (1998).

  13. 13.

    et al. Submicrometer axial resolution optical coherence tomography. Opt. Lett. 27, 1800–1802 (2002).

  14. 14.

    , , & Interferometric synthetic aperture microscopy. Nat. Phys. 3, 129–134 (2007).

  15. 15.

    , , , & Binary-phase spatial filter for real-time swept-source optical coherence microscopy. Opt. Lett. 32, 2375–2377 (2007).

  16. 16.

    , , , & High-resolution optical coherence tomography over a large depth range with an axicon lens. Opt. Lett. 27, 243–245 (2002).

  17. 17.

    & Bessel beam spectral-domain high-resolution optical coherence tomography with micro-optic axicon providing extended focusing range. Opt. Lett. 33, 1696–1698 (2008).

  18. 18.

    , , , & Extended focus depth for Fourier domain optical coherence microscopy. Opt. Lett. 31, 2450–2452 (2006).

  19. 19.

    , , & Common-path interferometer for frequency-domain optical coherence tomography. Appl. Opt. 42, 6953–6958 (2003).

  20. 20.

    & “Coherence radar” and “Spectral radar”—new tools for dermatological diagnosis. J. Biomed. Opt. 3, 21–31 (1998).

  21. 21.

    et al. Pathological correlates of late drug-eluting stent thrombosis—strut coverage as a marker of endothelialization. Circulation 115, 2435–2441 (2007).

  22. 22.

    Changing concepts of atherogenesis. J. Intern. Med. 247, 349–358 (2000).

  23. 23.

    Atherosclerosis. Nature 407, 233–241 (2000).

  24. 24.

    , , & Pathology of the vulnerable plaque. J. Am. Coll. Cardiol. 47, C13–C18 (2006).

  25. 25.

    , & μCT-based analysis of a new paradigm for vulnerable plaque rupture: cellular microcalcifications in fibrous caps. Mol. Cell. Biomech. 5, 37–47 (2008).

  26. 26.

    et al. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 373, 897–910 (2009).

  27. 27.

    ImageJ. (US National Institutes of Health, Bethesda, Maryland, 1997–2011).

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Acknowledgements

We wish to acknowledge contributions from D. Winsor-Hines of Boston Scientific for providing the stents that were used to create Supplementary Figure 4 , G. Veytsman of Capital Biosciences for providing explanted human hearts, and J. Zhao and the Wellman Center Photopathology Laboratory staff for expert histology processing. Swine arterial tissue was obtained from the Massachusetts General Hospital Knight Surgical Laboratory. Human tissue was provided by the National Disease Research Interchange and Capital Biosciences. Endothelial cells were supplied by the Schepens Eye Research Institute. This research was supported in part by the US National Institutes of Health (contracts R01HL076398 and R01HL093717) and the Cystic Fibrosis Foundation (contract TEARNE07XX0).

Author information

Affiliations

  1. Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Linbo Liu
    • , Joseph A Gardecki
    • , Seemantini K Nadkarni
    • , Jimmy D Toussaint
    • , Yukako Yagi
    • , Brett E Bouma
    •  & Guillermo J Tearney
  2. Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Linbo Liu
    • , Joseph A Gardecki
    • , Seemantini K Nadkarni
    • , Jimmy D Toussaint
    •  & Brett E Bouma
  3. Harvard-MIT Health Sciences and Technology, Cambridge, Massachusetts,USA

    • Seemantini K Nadkarni
    • , Brett E Bouma
    •  & Guillermo J Tearney
  4. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Yukako Yagi
    •  & Guillermo J Tearney

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Contributions

L.L. developed the μOCT system and participated in conducting the imaging studies and writing the manuscript. J.A.G. was responsible for procuring and preparing specimens, preparing the specimens for histopathology and organizing all digital histopathology data. S.K.N. and J.D.T. prepared the endothelial cell cultures. Y.Y. digitized the histopathology slides using her full-slide scanning systems. L.L. and G.J.T. analyzed and processed the data. B.E.B. contributed to the study design and participated in the analysis of the data. G.J.T. supervised the overall project and contributed to the design of experiments, interpretation of the μOCT image data and preparation of the manuscript. All authors read and edited the manuscript.

Competing interests

Massachusetts General Hospital has licensed OFDI technology to Terumo Corporation. B.E.B. and G.J.T. receive sponsored research relating to OFDI technology development from Terumo Corporation. B.E.B. and G.J.T. also have the right to receive royalty payments as part of this licensing arrangement.

Corresponding author

Correspondence to Guillermo J Tearney.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–4 and Supplementary Methods

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DOI

https://doi.org/10.1038/nm.2409

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