Endoluminal ultrasonographic and histologic evaluation of periurethral collagen injection

To determine the acute and chronic ultrasonographic and histologic characteristics of injected glutaraldehyde cross-linked collagen in an animal model in order to enhance the therapeutic efficacy of the delivery of collagen for the treatment of urinary incontinence, three different depths of endoluminal ultrasound-guided injection (submucosal, intramuscular, periadventitial) of collagen into the urethral and bladder walls in two Yucatan mini pigs were investigated. The ultrasonographic characteristics of the injected material were examined 1, 4, 8, and 12 weeks later. A separate set of collagen injections, into the dermis and intramuscular layer of the lateral thigh of the animals, was undertaken with small-parts ultrasound guidance and follow-up. The injected tissues of the bladder, urethra, and thigh were ultrasonographically and histologically examined 3 months post-injection. Acutely injected collagen appeared hypoechoic on ultrasonography, although echogenicity increased over time. Submucosally injected collagen remained contained, forming a discrete collection of the material, whereas periadventitially injected collagen dispersed immediately. The ultrasonographic appearance and size of collagen collections correlated directly with their histologic identification and measurement. Injected collagen generated little inflammatory reaction, although infiltration by histiofibroblasts and neovascularization of the injected collagen occurred. Submucosal collagen injection resulted in superior longevity compared with intramuscular injection. From the results of our study, we hypothesize that durable success with collagen injection for the treatment of urinary incontinence is attributable to histiofibroblast infiltration of the injected collagen. When injected collagen is replaced with a hypertrophic scar, long-lasting clinical success is likely. If the injected collagen is replaced with a contracted scar, however, urethral coaptation may not persist. Endoluminal ultrasonography is helpful in ensuring the accurate submucosal location of collagen injection and in avoiding dispersion of the material and should enhance therapeutic efficacy in the treatment of urinary incontinence.