Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

Abstract

Abstract. Gastrointestinal cancers are heterogeneous and can overexpress several protein targets that can be imaged simultaneously on endoscopy using multiple molecular probes. We aim to demonstrate a multispectral scanning fiber endoscope for wide-field fluorescence detection of colonic dysplasia. Excitation at 440, 532, and 635 nm is delivered into a single spiral scanning fiber, and fluorescence is collected by a ring of light-collecting optical fibers placed around the instrument periphery. Specific-binding peptides are selected with phage display technology using the CPC;Apc mouse model of spontaneous colonic dysplasia. Validation of peptide specificity is performed on flow cytometry and in vivo endoscopy. The peptides KCCFPAQ, AKPGYLS, and LTTHYKL are selected and labeled with 7-diethylaminocoumarin-3-carboxylic acid (DEAC), 5-carboxytetramethylrhodamine (TAMRA), and CF633, respectively. Separate droplets of KCCFPAQ-DEAC, AKPGYLS-TAMRA, and LTTHYKL-CF633 are distinguished at concentrations of 100 and 1 μM. Separate application of the fluorescent-labeled peptides demonstrate specific binding to colonic adenomas. The average target/background ratios are 1.71 AE 0.19 and 1.67 AE 0.12 for KCCFPAQ-DEAC and AKPGYLS-TAMRA, respectively. Administration of these two peptides together results in distinct binding patterns in the blue and green channels. Specific binding of two or more peptides can be distinguished in vivo using a novel multispectral endoscope to localize colonic dysplasia on real-time wide-field imaging.

Review of diverse optical fibers used in biomedical research and clinical practice

“…Other endoscope designs use a central fiber for illuminations and either another individual fiber or a circular array of fibers for image retrieval. [126][127][128][129][130][131] A major limitation when using MMFs is the temporal variation of the modal distributions in the fiber, which can lead to image flickering. Actually this situation occurs in all imaging systems that employ MMFs both for the delivery and the collection of light.…”

Spectrally enhanced imaging of occlusal surfaces and artificial shallow enamel erosions with a scanning fiber endoscope

“…Finally, the red channel consisted of light transmitted through the green beamsplitter. 16 Reflected light from the 405 and 444 nm illuminating lasers were collected in the blue channel and Fig. 1 Flow chart of the experiment.…”

“…[11][12][13] Although still in the research stage, this technology has potential to supplement x-ray microradiography due to its deep penetration depth. 14 A new laser-based ultrathin scanning fiber endoscope (SFE) technology 15 developed for cancer diagnosis 16 was used in this study for acquiring dental images. The thin and flexible endoscope offers advantages in its multi-modal capabilities.…”

Mitigating fluorescence spectral overlap in wide-field endoscopic imaging

“…[1][2][3][4][5][6][7] Fluorophore conjugates are routinely used to identify specific DNA components in flow cytometry systems, DNA microarrays, and microscopic histology examinations [e.g., fluorescence in situ hybridization (FISH)]. Over the past two decades, fluorophore optical probes have been evaluated for in vivo clinical imaging applications and to identify pre-or early stage cancerous conditions such as neoplastic lesions in human oral tissue, 8 dysplasia in colon, 9 highgrade dysplasia (HGD) in Barrett's esophagus (BE), 10 as well as screening and early detection for breast cancer, 11 bladder cancer, 5 and lung small cell carcinoma. 12 Meanwhile, in vivo molecular optical imaging has also been used in ovarian cancer surgery guidance 4 as well as for visualization and delineation of tumor margins.…”