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 na?ve 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.

Public Health Relevance

Evaluation of safety and efficacy of microbicides requires an assessment of potential injury caused by micobicides 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 imagedbased 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 na?ve 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 microbicideinduced 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
4R33AI076062-03
Application #
7934186
Study Section
Special Emphasis Panel (ZAI1-RB-A (M1))
Program Officer
Turpin, Jim A
Project Start
2007-09-30
Project End
2012-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
3
Fiscal Year
2009
Total Cost
$458,348
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Engineering (All Types)
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Vargas, Gracie; Vincent, Kathleen Listiak; Wei, Jingna et al. (2016) Topical injury evaluation of the murine colorectal mucosa using confocal endomicrosopy: a valuable method for assessing mucosal injuries associated with risk of pathogen transmission. J Microsc 264:227-237
Vargas, Gracie; Vincent, Kathleen Listiak; Zhu, Yong et al. (2016) In Vivo Rectal Mucosal Barrier Function Imaging in a Large-Animal Model by Using Confocal Endomicroscopy: Implications for Injury Assessment and Use in HIV Prevention Studies. Antimicrob Agents Chemother 60:4600-9
Bell, Brent A; Vincent, Kathleen L; Bourne, Nigel et al. (2013) Optical coherence tomography for assessment of microbicide safety in a small animal model. J Biomed Opt 18:046010
Vincent, Kathleen Listiak; Vargas, Gracie; Bourne, Nigel et al. (2013) Image-based noninvasive evaluation of colorectal mucosal injury in sheep after topical application of microbicides. Sex Transm Dis 40:854-9
Vincent, Kathleen L; Vargas, Gracie; Wei, Jingna et al. (2013) Monitoring vaginal epithelial thickness changes noninvasively in sheep using optical coherence tomography. Am J Obstet Gynecol 208:282.e1-7
Chitchian, Shahab; Vincent, Kathleen L; Vargas, Gracie et al. (2012) Automated segmentation algorithm for detection of changes in vaginal epithelial morphology using optical coherence tomography. J Biomed Opt 17:116004
Vargas, Gracie; Patrikeev, Igor; Wei, Jingna et al. (2012) Quantitative assessment of microbicide-induced injury in the ovine vaginal epithelium using confocal microendoscopy. BMC Infect Dis 12:48