Article

Multimodal laser-based angioscopy for structural, chemical and biological imaging of atherosclerosis

  • Nature Biomedical Engineering 1, Article number: 0023 (2017)
  • doi:10.1038/s41551-016-0023
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Abstract

The complex nature of atherosclerosis demands high-resolution approaches to identify subtle thrombogenic lesions and define the risk of plaque rupture. Here, we report the proof-of-concept use of a multimodal scanning fibre endoscope (SFE) consisting of a single optical fibre scanned by a piezoelectric drive that illuminates tissue with red, blue and green laser beams, and that digitally reconstructs images at 30 Hz with high resolution and large fields of view. By combining laser-induced reflectance and fluorescence emission of intrinsic fluorescent constituents in arterial tissues, the SFE allowed us to co-generate endoscopic videos with a label-free biochemical map to derive a morphological and spectral classifier capable of discriminating early, intermediate, advanced and complicated atherosclerotic plaques. We demonstrate the capability of scanning fibre angioscopy for the molecular imaging of vulnerable atherosclerosis by targeting proteolytic activity with a fluorescent probe activated by matrix metalloproteinases. We also show that the SFE generates high-quality spectral images in vivo in an animal model with medium-sized arteries. Multimodal laser-based angioscopy could become a platform for the diagnosis, prognosis, and image-guided therapy of atherosclerosis.

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Acknowledgements

This work was supported by Cerebrovascular Research Award, Joint Section on Cerebrovascular Surgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons, and the National Institutes of Health (NIH) U54 CA163059 (E.J.S. and T.D.W.), R01 EB016457 (E.J.S.), R01 HL129778 and R01 HL117491 (Y.E.C.), and R01CA200007 (E.J.S. and T.D.W.). The authors thank D. French, C. Prescott, D. Griffiths and J. Jentzen for their expertise and technical assistance in obtaining human cadaveric specimens. We are also grateful to M. Foldenauer for artwork assistance, J. Diaz for his endovascular expertise, and H. Wagner for editorial assistance.

Author information

Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Luis E. Savastano
    • , Aditya Pandey
    •  & B. Gregory Thompson
  2. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Quan Zhou
    • , Arlene Smith
    •  & Thomas D. Wang
  3. Department of Mechanical Engineering, University of Washington, Seattle, Washington 98195, USA

    • Karla Vega
    •  & Eric J. Seibel
  4. Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Carlos Murga-Zamalloa
    • , David Gordon
    •  & Jon McHugh
  5. University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA

    • Lili Zhao
  6. Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Michael M. Wang
  7. VA Ann Arbor Healthcare System, Ann Arbor, Michigan 48105, USA

    • Michael M. Wang
  8. Center for Advanced Models and Translational Sciences and Therapeutics, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, Michigan 48109-2800USA

    • Jie Xu
    • , Jifeng Zhang
    •  & Y. Eugene Chen
  9. Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Thomas D. Wang
  10. Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Thomas D. Wang

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Contributions

L.E.S. designed and performed the experiments and wrote the manuscript. Q.Z., A.S., K.V., C.M.-Z., D.G., J.M. and L.Z. analysed and processed the data. M.M.W. contributed to the design of experiments. A.P. and B.G.T. contributed to the design of experiments and provided surgical specimens. J.X., J.Z. and Y.E.C. contributed with the animal model and experiments. E.J.S. developed SFE technology and contributed to preparation of the manuscript. T.D.W. contributed to experiment design and manuscript preparation, and supervised the overall project. All authors read and edited the manuscript.

Competing interests

E.J.S. participates in royalty sharing with his employer, the University of Washington, which has ownership of patents that may gain or lose financially through this publication. The remaining authors declare no competing financial interests.

Corresponding author

Correspondence to Luis E. Savastano.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary figures, tables and video legends.

Videos

  1. 1.

    Supplementary Video 1

    Ex vivo spectral video angioscopy of a normal artery.

  2. 2.

    Supplementary Video 2

    Ex vivo spectral video angioscopy of an early lesion.

  3. 3.

    Supplementary Video 3

    Ex vivo spectral video angioscopy of an intermediate lesion.

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    Supplementary Video 4

    Ex vivo spectral video angioscopy of an advanced lesion.

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    Supplementary Video 5

    Ex vivo spectral video angioscopy of complicated plaques.

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    Supplementary Video 6

    In vivo spectral video angioscopy.