Comprehensive volumetric optical microscopy in vivo

Abstract

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

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Figure 1: Principles of comprehensive optical frequency-domain imaging (OFDI).
Figure 2: Comprehensive microscopy of a porcine esophagus in vivo.
Figure 3: Comprehensive microscopy of a porcine coronary artery in vivo.
Figure 4: Volumetric imaging of a stented porcine coronary artery in vivo.
Figure 5: Cross-sectional images of dissected coronary artery and histology comparison.

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Acknowledgements

This research was supported in part by the US National Institutes of Health (contracts R01 HL070039, R33 CA110130, R01 RR0119768, R01 HL076398 and R01 CA103769) and by the Terumo Corporation.

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Correspondence to Brett E Bouma.

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Competing interests

The authors have pending patent applications relating to the imaging technology described in this manuscript. A portion of the research described in this manuscript was provided by the Terumo Corporation through a sponsored research agreement with Massachusetts General Hospital.

Supplementary information

Supplementary Fig. 1

Optical frequency domain imaging system schematic. (PDF 221 kb)

Supplementary Video 1

OFDI movie of swine esophagus acquired in vivo. The x-axis corresponds to the azimuthal angle of the catheter from 0 to 2π, and the y-axis represents the radial coordinate (depth). To reduce the file size, the longitudinal segment length was limited to 3.7 mm, the individual images were downsampled and significant image compression was applied. The influence of the beating of the heart at a period of 1.4 s is seen. (MOV 1374 kb)

Supplementary Video 2

OFDI movie acquired during a pull-back of 2 cm in a swine coronary artery in vivo. The movie consists of 432 frames, significantly compressed from the original, which were acquired in 4 sec but displayed at a 3-fold decreased frame rate with an inverse grayscale lookup table. (AVI 2054 kb)

Supplementary Video 3

OFDI movie acquired in a human coronary artery in vitro. Although the anatomy of the human coronary arteries is similar to that of swine, minimum pathology will typically be present in the form of intimal hyperplasia as observed throughout this vessel. (AVI 1165 kb)

Supplementary Video 4

OFDI movie of beating Xenopus embryo heart. Full volume images were acquired (50 ms each) during beating of the embryo heart. At end diastole, the ventricle was dilated to its greatest volume whereas the volumes of the atrium and truncus were at their minima. In systole, it compresses and the truncus arteriosus expands and rotates. (AVI 2449 kb)

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Yun, S., Tearney, G., Vakoc, B. et al. Comprehensive volumetric optical microscopy in vivo. Nat Med 12, 1429–1433 (2006). https://doi.org/10.1038/nm1450

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