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: 7338388
• 负责人: Massoud Motamedi
• 金额: $ 18.91万
• 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 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7338388
• 关键词: AIDS/HIV problem; Address; Advanced Development; Animal Model; Animals; Architecture; Attention; Biological; Cervical; Characteristics; Classification; Clinical; Clinical Research; Colonoscopy; Colposcopy; Community Developments; Confocal Microscopy; Depth; Development; Diagnostic; Disruption; Effectiveness; Emerging Technologies; End Point; 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; Purpose; Range; Rectum; Reproducibility; Resolution; Safety; Science; Sexually Transmitted Diseases; Surface; System; Techniques; Technology; Testing; Time; Tissues; Topical application; Toxic effect; Vagina; base; caN protocol; genital infection; human subject; in vivo; instrument; instrumentation; microbicide; mouse model; novel; optical imaging; photonics; rectal; research and development; response; tomography

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(由申请人提供)：评估杀微生物剂的安全性和有效性需要评估杀菌剂对宫颈阴道和直肠上皮造成的潜在损害。局部应用杀菌剂后，可用于内窥镜下、快速和定量评估组织损伤的成像技术和方案的发展可能对杀菌剂在动物模型和临床研究中的开发和测试产生重大影响。不幸的是，目前的成像技术，如白光阴道镜或结肠镜，不能提供高分辨率的上皮损伤图像，也不能探测表面以下可能明显的上皮损伤和炎症。然而，近年来，新的成像技术已经发展起来，现在可以在体内进行具有显微分辨率的上皮组织的高分辨率成像。我们的总体目标是开发一种基于内窥镜成像的方法，可用于1)评估杀菌剂可能造成的伤害程度，以及2)将成像研究结果与小鼠对HSV-2引起的生殖器感染的易感性相关联。我们将采用新兴的高分辨率成像方法，包括共聚焦荧光显微镜和光学相干断层扫描(OCT)，以表征未处理的性初生小鼠以及使用已知刺激性杀菌剂处理的小鼠的宫颈、阴道和直肠上皮结构中发生的变化。这些结果将与使用具有良好特征的HSV-2感染小鼠模型的感染易感性相关。这将使我们能够评估基于杀菌剂诱导的上皮变化的共聚焦荧光和OCT成像对观察到的HSV-2易感性的预测价值，并关注结果的重复性/一致性。在这个项目的第一阶段，我们将展示高分辨率光学成像的能力，以定量评估宫颈阴道和直肠组织对已知杀菌剂的反应，并测试预测杀菌剂诱导的宫颈阴道敏感性变化的生物终点的能力。在第二阶段，建议的基于图像的直肠反应评估将被扩展，以建立基于图像的标记物与应用杀菌剂后的直肠敏感性之间的相关性。此外，将优化仪器和成像参数，使成像方案适用于大型动物模型和人类的宫颈阴道和直肠上皮反应成像。随着新产品的开发，我们还计划使用开发的成像方案来评估新型杀菌剂在小动物模型中的性能。