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High-resolution optical imaging assessment of microbicide toxicity

杀菌剂毒性的高分辨率光学成像评估

基本信息

批准号：
8072320
负责人：
Massoud Motamedi
金额：
$ 27.25万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8072320
关键词：
AIDS/HIV problem Address Advanced Development Animal Model Animals Architecture Attention Biological Cervical Characteristics Classification Clinical Clinical Research Colonoscopy Colposcopy Communities Confocal Microscopy Development Diagnostic Effectiveness Emerging Technologies Epithelial Epithelium Evaluation Fluorescence Fluorescence Microscopy Foundations Goals Growth Histology Human Human Herpesvirus 2 Image Imagery Imaging technology Infection Inflammation Inflammatory Response Injury Light Link Local Microbicides Methods Microscopic Microscopy Modality Modeling Morphology Mucous Membrane Mus Optical Coherence Tomography Optics Performance Phase Predictive Value Predisposition Prevention Protocols documentation Public Health Rectum Reproducibility Resolution Safety Science Sexually Transmitted Diseases Surface System Techniques Technology Testing Time Tissues Topical application Toxic effect Vagina base genital infection human subject imaging modality in vivo instrument instrumentation microbicide mouse model novel optical imaging photonics rectal research and development response

项目摘要

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 microbicide-induced changes in susceptibility in cervicovaginal tract. In phase II, the proposed imagedbased 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.

评价杀微生物剂的安全性和有效性需要评估潜在的伤害