Clinically compatible flexible wide-field multi-color fluorescence endoscopy with a porcine colon model

Abstract

Early detection of structural or molecular changes in dysplastic epithelial tissues is crucial for cancer screening and surveillance. Multi-targeting molecular endoscopic fluorescence imaging may improve noninvasive detection of precancerous lesions in the colon. Here, we report the first clinically compatible, wide-field-of-view, multi-color fluorescence endoscopy with a leached fiber bundle scope using a porcine model. A porcine colon model that resembles the human colon is used for the detection of surrogate tumors composed of multiple biocompatible fluorophores (FITC, ICG, and heavy metal-free quantum dots (hfQDs)). With an ex vivo porcine colon tumor model, molecular imaging with hfQDs conjugated with MMP14 antibody was achieved by spraying molecular probes on a mucosa layer that contains xenograft tumors. With an in vivo porcine colon embedded with surrogate tumors, target-to-background ratios of 3.36 ± 0.43, 2.70 ± 0.72, and 2.10 ± 0.13 were achieved for FITC, ICG, and hfQD probes, respectively. This promising endoscopic technology with molecular contrast shows the capacity to reveal hidden tumors and guide treatment strategy decisions. Sharma, "Comparison of the yield and miss rate of narrow band imaging and white light endoscopy in patients undergoing screening or surveillance colonoscopy: a meta-analysis," Am. J. Gastroenterol. 107(3), 363-371 (2012). 2. Sturm, M.B. and T.D. Wang," Emerging optical methods for surveillance of Barrett's oesophagus, " Gut, gutjnl-2013" Gut, gutjnl- -306706 (2015. Rat, P. Roignot, J. Faivre, P. Laurent-Puig, and F. Piard, "Mutations in the RAS-MAPK, PI (3) K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers," Int.

Bimodal reflectance and fluorescence multispectral endoscopy based on spectrally resolving detector arrays

“…As suggested above, an SRDA could therefore be integrated as a "chip-on-tip" at the distal end of a commercial endoscope in future. This is beneficial when compared to multispectral systems based on filter wheels 21,30,31 and tunable filters, 23,32 which sacrifice temporal resolution to sequentially acquire spectral data. Sequential acquisition of spectral data can also introduce motion artifacts between sequentially acquired spectral band images.…”

“…Spectral imaging is typically achieved by filtering the light on either the illumination or detection side. Filtering has been achieved by the use of: a set of dichroic beamsplitters and dedicated detectors; 10,27,29 a filter wheel with a set of bandpass filters; 21,30,31 tunable filters; 23,32 or a monochromator. 33 Alternatively, a set of laser lines may be used for illumination.…”

Multi-Spectral Fluorescence Imaging of Colon Dysplasia In Vivo Using a Multi-Spectral Endoscopy System

“…Specific details of the channel insert-type endoscope system are described in the literature [33] and schematic is shown in Figure 4 A . Briefly, the device is fabricated with flexible and miniaturized fiber-optic probe for the compatibility with clinical endoscope in non-contact mode.…”

Advantages of patient‐derived orthotopic mouse models and genetic reporters for developing fluorescence‐guided surgery

“…When developing clinical fluorescence imaging devices, the size of organ and organ spaces must be closer to humans. Porcine models have been used to evaluate fluorescence enabled laparoscopes, thoracoscopes, endoscopes, with non-specific fluorescent dyes like ICG[41,42]. While these larger animal models cannot effectively model human cancers, the development advanced reproductive technologies and ability to introduce genome modifications through approaches such as CRISPR, larger oncologic animal models such as the oncopig will become available[43].…”