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 8mL dose of 0.2% BZK (benzalkonium chloride) solution or PBS control. Imaging was performed before and 30 minutes after treatment. Colonoscopy findings were evaluated based on mucosal disruption. OCT images were graded based on the integrity of the mucosal layer. Biopsies collected post-treatment were evaluated by histology for validation of OCT scoring. Results Mucosal disruption was observed by colonoscopy in BZK-treated animals, while 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. Since 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.

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