Multimodal endoscopy for colorectal cancer detection by optical coherence tomography and near-infrared fluorescence imaging

Abstract

While colonoscopy is the gold standard for diagnosis and classification of colorectal cancer (CRC), its sensitivity and specificity are operator-dependent and are especially poor for small and flat lesions. Contemporary imaging modalities, such as optical coherence tomography (OCT) and near-infrared (NIR) fluorescence, have been investigated to visualize microvasculature and morphological changes for detecting early stage CRC in the gastrointestinal (GI) tract. In our study, we developed a multimodal endoscopic system with simultaneous co-registered OCT and NIR fluorescence imaging. By introducing a contrast agent into the vascular network, NIR fluorescence is able to highlight the cancer-suspected area based on significant change of tumor vascular density and morphology caused by angiogenesis. With the addition of co-registered OCT images to reveal subsurface tissue layer architecture, the suspected regions can be further investigated by the altered light scattering resulting from the morphological abnormality. Using this multimodal imaging system, an in vivo animal study was performed using a F344-Apc^PircUwm rat, in which the layered architecture and microvasculature of the colorectal wall at different time points were demonstrated. The co-registered OCT and NIR fluorescence images allowed the identification and differentiation of normal colon, hyperplastic polyp, adenomatous polyp, and adenocarcinoma. This multimodal imaging strategy using a single imaging probe has demonstrated the enhanced capability of identification and classification of CRC compared to using any of these technologies alone, thus has the potential to provide a new clinical tool to advance gastroenterology practice.

Fig. 1

(a) Overall design of endoscopic multimodality OCT and NIR fluorescence system. (b) Multimodality imaging probe. WDM: wavelength division multiplexer. PMT: photomultiplier tube. DCF coupler: double clad fiber coupler. OCT: optical coherence tomography. CW: continuous wavelength. GRIN: gradient index.

Fig. 2

Unfolded NIR fluorescence images of rectal wall with different time points. (a) NIR fluorescence image at week 1. (b) NIR fluorescence image at week 4. (c) NIR fluorescence image at week 8. (d) Photo of the excised rectum. Scale bar: 1mm

Fig. 3

Combined OCT and NIR fluorescence B-scan images of colorectal wall with different time points: (I) week 1, (II) week 4, (III) week 8. Green dashed boxes: abnormal lesions. Yellow arrows: small gaps between different layers.

Fig. 4

Combined OCT and NIR fluorescence images and en face NIR fluorescence images of colorectal wall. (a)-(f) Combined OCT and NIR fluorescence images at different longitudinal positions. (g) En face NIR fluorescence images.

Fig. 5

3D OCT and NIR fluorescence images. (a)-(f) En face 3D images of colorectal wall with different views (field of view: 0°-360°). (g)-(h) Volumetric 3D images of colorectal wall (field of view: 0°-250°).

Fig. 6

Normal rectum. (a) The combined OCT and NIR fluorescence image. (b) Enlarged view of the dashed box in (a). (c) Histology. M: mucosa; SM: submucosa; MP: muscularis propria.

Fig. 7

Hyperplastic polyp. (a) The combined OCT and NIR fluorescence image. (b) Enlarged view of the dashed box in (a). (c) Histology. HP: hyperplastic polyp.

Fig. 8

Adenomatous polyp. (a) The combined OCT and NIR fluorescence image. (b) Enlarged view of the dashed box in (a). (c) Histology. AP: adenomatous polyp.

Fig. 9

Adenocarcinoma. (a) The combined OCT and NIR fluorescence image. (b) Enlarged view of the dashed box in (a). (c) Histology.