Flexible endoscope for continuous in vivo multispectral fluorescence lifetime imaging

Abstract

Fluorescence lifetime imaging (FLIM) offers a noninvasive approach for characterizing the biochemical composition of biological tissue. There has been an increasing interest in the application of multispectral FLIM for medical diagnosis. Central to the clinical translation of FLIM technology is the development of compact and high-speed endoscopy systems. Unfortunately, the predominant multispectral FLIM approaches suffer from limitations that impede the development of endoscopy systems that are suitable for in vivo tissue imaging. We present a compact wide-field time-gated FLIM flexible endoscope capable of continuous lifetime imaging of up to three fluorescence emission bands simultaneously. This novel endoscope design will facilitate the evaluation of FLIM for in vivo applications.

Handheld multispectral fluorescence lifetime imaging system for in vivo applications

“…We are thus confident that in vivo imaging can be performed safely with the proposed handheld FLIM imaging system. One significant advantage of the proposed multispectral FLIM endoscope design is that, unlike previous implementations [3,4,7,9], it can achieve relatively high imaging speed without sacrificing temporal resolution. The achieved high temporal resolution allows correcting for the non-ideal instrument response through time deconvolution.…”

“…Second, since illumination light is delivered through a fiber adjacent to the imaging bundle, achieving uniform illumination and endoscope compactness can be challenging. The second design addressed these two limitations and was used to image in vivo malignant lesions in a hamster cheek pouch model of oral epithelial cancer [9]. However, in order to achieve fast FLIM imaging, a rapid lifetime determination (RLD) algorithm had to be adopted, limiting its temporal resolution.…”

A flexible wide‐field FLIM endoscope utilising blue excitation light for label‐free contrast of tissue

“…This approach has been successfully translated to in vivo studies in hamster [24] and human [25] and has the advantage that the low duty cycle time-gated imaging enables FLIM in the presence of background room lights. Recently it has been extended to multispectral FLIM endoscopy [26] employing a frequency-tripled Q-switched Nd : YAG laser as the excitation source (wavelength 355 nm, repetition rate 100 kHz, pulse length <1 ns) and, using a twogate rapid lifetime determination algorithm, has achieved FLIM at 2 frames per second in three spectral channels imaging a hamster cheek pouch model of cancer in vivo.…”

Discovery of specific targeting ligands as the biomarkers for colorectal cancer

“…If CRC-9 is proved specific to human CRC, It is possible to tag these peptides with fluorescein dye which if subsequently bound to colon cancer cells would highlight such changes in the target tumors on fluorescent microscopy or with special epifluorescent endoscopy [36]. Another potential application of this biomarker could be in the early diagnosis of dysplastic or premalignant changes in patients with chronic inflammatory bowel disease.…”

“…At this stage of exploratory study, we only tested the peptide ligand against colon cancer cell lines and nude mice bearing CRC xenografts. If CRC-9 is proved specific to human CRC tissues, it is possible to tag these peptides with fluorescein dye to visualize tumors on fluorescent microscope or with special epifluorescent endoscopy [36].…”