Title: Distribution of Topical Medication in the Human Vagina as Imaged by MRI
Abstract: Introduction: Although new topical microbicides are under development for sexually transmitted disease (STD) and human immunodeficiency virus (HIV) prophylaxis, there is little information about the expected and optimal intravaginal distributions of these products. We do not know, for example, what volume of gel is required to cover the vaginal mucosa, whether coverage is evenly distributed, how long the gel takes to distribute to all parts of the vagina, whether ambulation augments or hinders distribution of the gel, or how long mucosal coverage from a gel can be expected to last. This study was performed to assess the use of Magnetic Resonance Imaging (MR) to determine the varying distribution of an intravaginally placed gel over time and with different levels of patient activity. Design: Prospective evaluation of a novel in vivo imaging technique. Materials and Methods: Commercially available topical spermicide was mixed with Gadolinium-chelate MR contrast material and introduced with a standard applicator. T1-weighted 3-dimensional MR images were acquired to assess the distribution of the intravaginally placed gel. Spread of the gel was quantified with measurement in the anterior-posterior and transverse planes at five demarcated sites in the vagina; just below the cervix, as the vagina passed through the pelvic diaphragm, in the mid portion of the lower vagina, just above the introitus and in the posterior vaginal fornix. Results: In all trials, the initial bolus of gel was delivered into the upper portion of the vagina, above the urogenital diaphragm. Thereafter, it spread into the vaginal fornices and "flattened" to cover the lateral aspects of the vagina. Without ambulation, the majority of this early spread was confined to the upper vagina. With ambulation and longer elapsed time, there was further spread of gel in the upper vagina, as well as spread into the lower vagina and a concomitant significant increase in overall vaginal surface coverage. Overall Surface Contact increased from 52.8% (59.8/112.9) initially (time zero) to 57.4% (64.7/112.9) at 6–10 minutes [P=0.19] and to 70.1% (79.1/112.9) at 20–30 minutes [P=0.007] without ambulation. Ambulation significantly increased Surface Contact from 57.75% (65.2/112.9) to 65.9% (74.4/112.9) [P=0.04] 20 minutes after insertion. Surface Contact increased significantly after 6 hours from 65.8% (74.3/112.9) at 20 minutes to 96.9% (109.5/112.9) at 6 hours [P=0.009]. Conclusion: MR imaging can be used to monitor the spread of vaginally placed products and demonstrates significant increased spread with time and ambulation. This method can be used to evaluate the vaginal coverage of topical vaginal drugs used for prevention and treatment.