High-resolution optical imaging assessment of microbicide toxicity

Summary

Principal Investigator: Massoud Motamedi
Abstract: Evaluation of safety and efficacy of microbicides requires an assessment of potential injury caused by microbicides in the epithelium of cervicovaginal tract and rectum. The development of imaging technology and protocols that can be used for endoscopic, rapid, and quantitative assessment of tissue injury following topical application of microbicides could have significant impact on the development and testing of microbicides in animal models and clinical studies. Unfortunately, current imaging technology such as white light colposcopy or colonoscopy cannot provide high resolution images of epithelial injury and cannot probe below the surface where epithelial injury and inflammation may be evident. However, in recent years, new imaging technology has been developed where it is now possible to perform high resolution imaging of epithelial tissue with microscopic resolution in vivo. Our overall goal is to develop an endoscopic imaged based approach that can be used to 1) assess the degree of injury that may be induced by microbicides and 2) correlate the results of imaging studies to susceptibility to genital infection in mice cervicovaginal tract and rectum caused by HSV-2. We will deploy emerging high resolution imaging modalities including confocal fluorescence microscopy and optical coherence tomography (OCT) to characterize the changes that occur in the architecture of cervical, vaginal, and rectal epithelium of untreated sexually nave mice as well as mice treated with known irritative microbicides. These results will be correlated to susceptibility to infection using a well characterized mouse model of HSV-2 infection. This will allow us to assess the predictive value of confocal fluorescence and OCT imaging for observed HSV-2 susceptibility based on microbicide-induced epithelial changes with attention to reproducibility/consistency of findings. In phase I of this project we will demonstrate the capabilities of high resolution optical imaging to quantitatively assess the response of cervicovaginal and rectal tissue to known microbicides and test the ability to predict the biological end point of microbicide-induced changes in susceptibility in cervicovaginal tract. In phase II, the proposed imaged based assessment of rectal response will be extended to establish correlation between image-based markers and rectal susceptibility following application of microbicides. Furthermore, instrumentation and imaging parameters will be optimized to make the imaging protocol suitable for imaging of cervicovaginal and rectal epithelial response in large animal models and humans. We also plan to use the developed imaging protocol to assess the performance of novel microbicides in small animal models as new products are developed.
Funding Period: 2007-09-30 - 2010-08-31
more information: NIH RePORT

Top Publications

  1. pmc Estradiol improves genital herpes vaccine efficacy in mice
    Jeffry W Pennock
    Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Vaccine 27:5830-6. 2009
  2. pmc Quantitative assessment of microbicide-induced injury in the ovine vaginal epithelium using confocal microendoscopy
    Gracie Vargas
    Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, TX, USA
    BMC Infect Dis 12:48. 2012
  3. ncbi Influence of methamphetamine on genital herpes simplex virus type 2 infection in a mouse model
    Frances Valencia
    Department of Experimental Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Sex Transm Dis 39:720-5. 2012
  4. pmc Optical coherence tomography for assessment of microbicide safety in a small animal model
    Brent A Bell
    University of Texas Medical Branch, Center for Biomedical Engineering, 301 University Boulevard, Galveston, Texas 77555 1156, USA
    J Biomed Opt 18:046010. 2013

Detail Information

Publications4

  1. pmc Estradiol improves genital herpes vaccine efficacy in mice
    Jeffry W Pennock
    Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Vaccine 27:5830-6. 2009
    ....
  2. pmc Quantitative assessment of microbicide-induced injury in the ovine vaginal epithelium using confocal microendoscopy
    Gracie Vargas
    Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, TX, USA
    BMC Infect Dis 12:48. 2012
    ..High resolution imaging to assess epithelial integrity in a noninvasive manner could be a valuable tool for preclinical testing of candidate topical agents...
  3. ncbi Influence of methamphetamine on genital herpes simplex virus type 2 infection in a mouse model
    Frances Valencia
    Department of Experimental Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Sex Transm Dis 39:720-5. 2012
    ..METH is known to have immune modulatory properties. However, the impact of METH on normal immune responses and disease pathogenesis with STIs has not been fully examined...
  4. pmc Optical coherence tomography for assessment of microbicide safety in a small animal model
    Brent A Bell
    University of Texas Medical Branch, Center for Biomedical Engineering, 301 University Boulevard, Galveston, Texas 77555 1156, USA
    J Biomed Opt 18:046010. 2013
    ..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...