Development of an image based technique for assessment of colorectal epithelial integrity and function in an ovine model

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Damage to the intestinal epithelium can cause alterations in barrier permeability and may lead to an inflammatory state. This alteration in permeability may lead to or be a consequence of several disease states. Confocal endomicroscopy (CE) is an emerging technology capable of assessing mucosal permeability and structure during endoscopy. Chapter 2 assesses the alteration in rectal permeability in an ovine model induced by introduction of the microbicidal agent benzalkonium chloride (BZK). The study utilizes CE to demonstrate that BZK causes a significant increase in permeability on a 3-point visual grading scale as assessed by three graders between untreated (1.19 ± 0.53) and BZK treated (2.55 ± 0.75) tissues. Increased permeability may result in increased susceptibility to infections such as HIV. Chapter 3 expands on the permeability measures performed in Chapter 2 by introducing a novel quantitative grading technique. This method utilizes the grey level co-occurrence matrix (GLCM) texture analysis technique to compute the correlation statistic for each image. ROC analysis produces an ideal cut-off point for determining an increase in permeability with a resultant sensitivity and specificity of 95.5%. Quantitative permeability measures expand the applications of CE permeability assessment and strengthen its use in real time assessment of functional permeability in the clinic. Chapter 4 applies this newly developed technique to an ovine model in which estrogen and progesterone levels are altered. Past studies indicate that estrogen strengthens tight junctions and reduces permeability of the gut when present. This study finds that sheep that have been hormonally suppressed with depot medroxyprogesterone have a high permeability with 50% of sites showing increased permeability via the GLCM method developed in Chapter 3. Estrous phase normally cycling sheep have increased permeability in only 12.5% of sites. This study further finds other differences between hormonal states in the form of inflammation and epithelial gaps. The combination of quantitative permeability assessment with the structural information gathered by CE makes it an emerging technique that may expand our ability to diagnose and treat numerous gastrointestinal diseases during routine endoscopy.

confocal microscopy, endomicroscopy, microbicide, inflammatory bowel disease, irritable bowel syndrome, texture analysis