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

Nature Medicine volume 17, pages 1010–1014 (2011)Cite this article

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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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Figure 1: μOCT images of a fibrocalcific human cadaver coronary plaque.
Figure 2: μOCT of superficial arterial morphology.
Figure 3: μOCT of plaque morphology in human cadaver specimens.
Figure 4: μOCT of stent and neointimal morphology in human cadaver specimens.

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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).

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Authors and 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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  1. Linbo Liu
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  7. 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.

Corresponding author

Correspondence to Guillermo J Tearney.

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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.

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Liu, L., Gardecki, J., Nadkarni, S. et al. Imaging the subcellular structure of human coronary atherosclerosis using micro–optical coherence tomography. Nat Med 17, 1010–1014 (2011). https://doi.org/10.1038/nm.2409

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