title: Optical coherence tomography for assessment of microbicide safety in a small animal model.
abstract: Sensitive imaging techniques for small animals are needed to assess drug toxicity in preclinical studies. Optical coherence tomography (OCT) provides a noninvasive tool for high-resolution, depth-resolved visualization of drug-induced changes in tissue morphology. In a mouse model, we utilize OCT to assess vaginal tissue integrity following the application of topical microbicides (drugs used to prevent infection). Mice are challenged with herpes simplex virus-2 (HSV-2) to determine the correlation of tissue damage as quantified by OCT to increased susceptibility. The microbicide benzalkonium chloride (BZK) (0.02, 0.2, or 2%) or phosphate buffered saline control is administered intravaginally. In vivo OCT imaging and collection of tissue samples are performed after treatment. A quantitative OCT scoring system is applied to assess epithelial damage, and the results are compared with those of histology. A separate group of mice are treated similarly then challenged with HSV-2. Epithelial morphology quantified noninvasively by OCT and histology are dose-dependent (p<0.0001). The OCT scoring system detected a significant increase in epithelial damage with increasing BZK concentration (p<0.0001). These results paralleled an increase in HSV-2 susceptibility (p<0.005). OCT can be used as a noninvasive tool to assess topical drug toxicity in a small animal model with potential to predict increased susceptibility to vaginal infection.
authors.affiliation: University of Texas Medical Branch, Center for Biomedical Engineering, 301 University Boulevard, Galveston, Texas 77555-1156, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Bell
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Vincent
authors.forename: Nigel
authors.initials: N
authors.lastname: Bourne
authors.forename: Gracie
authors.initials: G
authors.lastname: Vargas
authors.forename: Massoud
authors.initials: M
authors.lastname: Motamedi
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D001548:Benzalkonium Compounds / Q000633:toxicity; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D006558:Herpes Genitalis / Q000382:microbiology; D018258:Herpesvirus 2, Human / Q000472:pathogenicity; D006651:Histocytochemistry; D051379:Mice; D041623:Tomography, Optical Coherence / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*; D014621:Vagina / Q000737:chemistry / Q000187:drug effects / Q000473:pathology / Q000821:virology
chemical_list: D000890:Anti-Infective Agents; D001548:Benzalkonium Compounds