Skip Navigation LinksHome > November 2013 - Volume 40 - Issue 11 > Image-Based Noninvasive Evaluation of Colorectal Mucosal Inj...
Sexually Transmitted Diseases:
doi: 10.1097/OLQ.0000000000000039
Original Study

Image-Based Noninvasive Evaluation of Colorectal Mucosal Injury in Sheep After Topical Application of Microbicides

Vincent, Kathleen Listiak MD*†; Vargas, Gracie PhD†‡; Bourne, Nigel PhD§¶; Galvan-Turner, Valerie MD*; Saada, Jamal I. MSc; Lee, Gabriel H. MD; Sbrana, Elena MD**; Motamedi, Massoud PhD†,††

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Abstract

Background

Successful development of topical rectal microbicides requires preclinical evaluation in suitable large animal models. Our previous studies have demonstrated the benefits of high-resolution optical coherence tomography (OCT) to visualize subclinical microbicide toxicity in the sheep vagina. In the current study, we evaluated the potential application of colonoscopy and OCT to visualize and quantify the effects of topical products on sheep colorectal tissue, as assessed by advanced imaging techniques.

Methods

Yearling virginal female sheep were treated rectally with a single 8-mL dose of 0.2% benzalkonium chloride (BZK) solution or phosphate-buffered saline control. Imaging was performed before and 30 minutes after treatment. Colonoscopy findings were evaluated based on mucosal disruption. Optical coherence tomography images were graded based on the integrity of the mucosal layer. Biopsies collected after treatment were evaluated by histology for validation of OCT scoring.

Results

Mucosal disruption was observed by colonoscopy in BZK-treated animals, whereas none was present in controls. In contrast to colonoscopy, high-resolution in-depth OCT imaging provided visualization of the morphology of the mucosal layer and underlying muscularis, thus enabling detection of microscopic abnormalities. Noninvasive quantification of drug-induced injury after validation of the scoring system (categories 1, 2, 3) showed increased scores after treatment with BZK (P < 0.001), indicating mucosal injury.

Conclusions

High-resolution OCT can be used as highly sensitive tool to evaluate rectal microbicide effects. Because the sheep rectum has both gross and microscopic similarities to the human, this model is a useful addition to current methods of rectal product toxicity.

Copyright © 2013 American Sexually Transmitted Diseases Association All rights reserved.

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