Abstract
Inflammatory bowel disease (IBD) is typically diagnosed by exclusion years after its onset. Current diagnostic methods are indirect, destructive, or target overt disease. Screening strategies that can detect low-grade inflammation in the colon would improve patient prognosis and alleviate associated healthcare costs. Here, we test the feasibility of fluorescence lifetime imaging (FLIm) to detect inflammation from thick tissue in a non-destructive and label-free approach based on tissue autofluorescence. A pulse sampling FLIm instrument with 355 nm excitation was coupled to a rotating side-viewing endoscopic probe for high speed (10 mm/s) intraluminal imaging of the entire mucosal surface (50–80 mm) of freshly excised mice colons. Current results demonstrate that tissue autofluorescence lifetime was sensitive to the colon anatomy and the colonocyte layer. Moreover, mice under DSS-induced colitis and 5-ASA treatments showed changes in lifetime values that were qualitatively related to inflammatory markers consistent with alterations in epithelial bioenergetics (switch between -oxidation and aerobic glycolysis) and physical structure (colon length). This study demonstrates the ability of intraluminal FLIm to image mucosal lifetime changes in response to inflammatory treatments and supports the development of FLIm as an in vivo imaging technique for monitoring the onset, progression, and treatment of inflammatory diseases.
Highlights
Inflammatory bowel disease (IBD) is expected to affect 10 million people in the Western world by 2030 [1]
The current results demonstrate that fluorescence lifetime imaging (FLIm) with 355 nm excitation was sensitive to the fluorescence from the epithelial layer and show that autofluorescence lifetime varies along the distinct anatomical regions of the colon
These results demonstrate that FLIm is sensitive to severe inflammation, as lifetime values under dextran sodium sulfate (DSS)-induced colitis were significantly altered compared to reference mock levels, and comparable to mock under 5-aminosalicylic acid (5-ASA) treatment
Summary
Inflammatory bowel disease (IBD) is expected to affect 10 million people in the Western world by 2030 [1]. Despite the fact that treatments for inflammatory disease have improved in the last decades, screening remains the strategy with the best real impact on reducing the incidence and early detection is key in preventing complications (i.e., IBD-induced colorectal cancer) [6,7]. The most established methods to diagnose IBD are either non-invasive and indirect (i.e., stool calprotecting or serological biomarkers) [4], or destructive (biopsybased). Endoscopic imaging has gained traction as an in situ method to visualize inflammation [8,9,10] and is instrumental to diagnosing IBD and its subtypes (ulcerative colitis and Crohn’s disease) [11,12]. New endoscopic strategies to directly detect early signs of inflammation on the colon mucosa would improve patient’s prognosis and alleviate the health care associated costs of disease management
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