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

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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Figure 1: Scanning fibre endoscope optics and fluorescence spectrometry of major structural constituents of atherosclerotic plaques.
Figure 2: Multimodal endoluminal angioscopy of normal carotid artery and early lesion.
Figure 3: Multimodal endovascular scanning fibre angioscopy of intermediate and advanced lesions.
Figure 4: Multimodal endovascular SFA of complicated plaques.
Figure 5: Multimodal endovascular scanning fibre angioscopy of proteolytic activity in endarterectomy specimen.
Figure 6: In vivo angioscopy in rabbit.

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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.

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Authors

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.

Corresponding author

Correspondence to Luis E. Savastano.

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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.

Supplementary information

Supplementary Information

Supplementary figures, tables and video legends. (PDF 407 kb)

Supplementary Video 1

Ex vivo spectral video angioscopy of a normal artery. (MP4 17698 kb)

Supplementary Video 2

Ex vivo spectral video angioscopy of an early lesion. (MP4 20672 kb)

Supplementary Video 3

Ex vivo spectral video angioscopy of an intermediate lesion. (MP4 18921 kb)

Supplementary Video 4

Ex vivo spectral video angioscopy of an advanced lesion. (MP4 21564 kb)

Supplementary Video 5

Ex vivo spectral video angioscopy of complicated plaques. (MP4 22770 kb)

Supplementary Video 6

In vivo spectral video angioscopy. (MP4 25427 kb)

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Savastano, L., Zhou, Q., Smith, A. et al. Multimodal laser-based angioscopy for structural, chemical and biological imaging of atherosclerosis. Nat Biomed Eng 1, 0023 (2017). https://doi.org/10.1038/s41551-016-0023

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