High-resolution optical imaging assessment of microbicide toxicity

杀菌剂毒性的高分辨率光学成像评估

• 批准号: 7940900
• 负责人: Massoud Motamedi
• 金额: $ 46.74万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940900
• 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

DESCRIPTION (provided by applicant): 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.

描述（通过应用提供）：评估微生物的安全性和效率需要评估宫颈上皮和直肠上皮中菌心造成的潜在损伤。在局部应用微生物剂时，可用于对组织损伤的内窥镜，快速和定量评估的成像技术和方案的开发可能会对动物模型和临床研究中菌心的发展和测试产生重大影响。不幸的是，当前的成像技术（例如白光阴道镜检查或结肠镜检查）无法提供上皮损伤的高分辨率图像，并且无法在表面以下探测上皮损伤和感染的表面。但是，近年来，已经开发出新的成像技术，现在可以在体内对具有微观分辨率的上皮组织进行高分辨率成像。我们的总体目标是开发一种基于内窥镜成像的方法，该方法可用于1）评估菌心可能诱导的损伤程度，以及2）将成像研究结果与HSV-2引起的小鼠颈椎和直肠的生殖器感染的敏感性相关联。我们将部署新出现的高分辨率成像模态，包括共焦荧光显微镜和光学相干断层扫描（OCT），以表征宫颈，阴道和未经治疗的性na¿ve ve ve ve ve小鼠的宫颈，阴道和直肠上皮的结构中发生的变化，并用已知的刺激性贴贴型刺激性小鼠处理。这些结果将与使用HSV-2感染的小鼠模型相关，与感染的易感性相关。这将使我们能够评估共焦荧光和OCT成像的预测值，以基于菌心诱导的上皮变化，对发现的重现/一致性的观察到的HSV-2敏感性。在该项目的第一阶段中，我们将证明高分辨率光学成像的能力，以定量评估颈胆碱和直肠组织对已知杀菌剂的反应，并测试预测颈昔肽剂易感性变化的能力。在第二阶段，将扩展基于成像的直肠反应的评估，以在应用菌皮剂后建立基于图像的标记与直肠敏感性之间的相关性。此外，将优化仪器和成像参数，以使大型动物模型和人类中宫颈阴道和直肠上皮反应的成像成像。我们还计划使用开发的成像协议来评估小动物模型中新型微生物的性能，因为开发了新产品。