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

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Abstract

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.

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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.

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Acknowledgements

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

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.

Correspondence to Farouc A Jaffer or Guillermo J Tearney.

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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)

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