Novel Coherence Imaging to Evaluate the Health of the Cervical Epithelium

用于评估宫颈上皮健康状况的新型相干成像

• 批准号: 9212788
• 负责人: Adam Wax
• 金额: $ 59.56万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9212788
• 关键词: Adopted; Advocate; Area; Barrett Esophagus; Biomedical Engineering; Biophotonics; Biopsy; Cancer Etiology; Cervical; Cervical Intraepithelial Neoplasia; Cervical dysplasia; Cervix Uteri; Cessation of life; Characteristics; Clinic; Clinical; Clinical Research; Colposcopy; Complex; Cytology; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Dysplasia; Epithelial; Epithelium; Evaluation; Exocervix; Fiber; Fostering; Gel; Goals; Health; Histology; Histopathology; Human; Human Papillomavirus; Image; Interferometry; Lesion; Lighting; Localized Lesion; Malignant neoplasm of cervix uteri; Manuals; Maps; Measurement; Measures; Metaplastic; Methods; Modality; Morbidity - disease rate; Morphology; Nuclear; Optics; Pap smear; Participant; Patients; Performance; Pilot Projects; Premalignant; Public Health; Research; Research Project Grants; Resolution; Risk; Scanning; Sensitivity and Specificity; Site; Specificity; Techniques; Technology; Tissues; Vagina; Validation; Woman; Work; anti-HIV microbicide; base; cohort; digital; field study; imaging approach; imaging platform; improved; in vivo; instrument; novel; operation; optical imaging; prototype; public health relevance; screening; standard of care; tool

DESCRIPTION (provided by applicant): Cervical cancer is a significant cause of morbidity in the U.S. with approximately 12,200 new cases and 4,200 deaths from this disease each year. As a screening tool, cervical cytology (the Papanicolaou smear) can reduce morbidity by detecting precancerous lesions; but it cannot locate dysplastic regions of the cervix, a necessity for biopsy guidance and therapy. Currently, regions suspected to be dysplastic are found by colposcopy with aceto-whitening, but this is a subjective diagnostic with limited accuracy and wide variability. The goal of this research project is to develop a novel coherence imaging platform for practical detection of cervical dysplasia. Reaching this goal will improve diagnosis and understanding of disease development. Many optical techniques have been proposed for detecting pre-cancerous lesions in the cervix, but none has yet been widely adopted, due primarily to limited performance. While high resolution methods show good sensitivity, the need to manually scan a probe across the ectocervix limits utility. In comparison, wide area imaging approaches examine more tissue area, but show limited specificity. Here we propose to create an imaging platform based on a multi-modality approach, combining wide field imaging, using multiplexed low coherence interferometry (mLCI) for comprehensive cervical mapping, with high resolution, depth-resolved nuclear morphology measurements, using angle-resolved LCI(a/LCI) for highly sensitive detection of dysplasia. The long term objective of this research is to create multi-modal instrument to enable diagnosis of cervical dysplasia. The following Specific Aims are proposed. 1) Develop multiplexed LCI for mapping the epithelial types of the cervix. The mLCI probe will conduct wide area scans of the ectocervix to map the squamous-to- columnar transition zone (T-zone). A proof of principle study at Duke will validate the mLCI probe, followed by a broader study at UCSF. Data will be compared to colpophotography, the current standard for assessing the T-zone. 2) Adapt angle-resolved LCI for detection of cervical dysplasia. a/LCI can detect dysplastic lesions via depth resolved nuclear morphology measurements. An initial in vivo pilot study will be conducted using an existing prototype and an optimized instrument will be developed to scan the ectocervix without needing to reposition the probe. The instrument will be used for proof of principle studies at Duke and then validated in a broader study at UCSF. To assess accuracy, a/LCI nuclear morphology measurements will be compared to histopathological evaluation of co-registered physical biopsies. 3) Integration of mLCI and a/LCI into a single imaging platform. The integrated platform will enable wide area mLCI scans, to map the T-zone of the cervix and serve as a guide for a/LCI nuclear morphology measurements to identify dysplasia at selected points. The instrument will be used in a pilot study at Duke and then applied in a clinical field test at UCSF. The optical imaging measurements will be compared to digital colpophotography to validate the T-zone mapping and to co-registered physical biopsies to confirm alignment of nuclear morphology with histopathological tissue state.

描述（由申请人提供）：宫颈癌是美国发病率的重要原因，每年约有1200例新病例和4,200例死亡。作为筛查工具，宫颈细胞学（Papanicolaou涂片）可以通过检测癌前病变来降低发病率。但是它无法找到子宫颈的发育不良区域，这是进行活检指导和治疗的必要性。目前，通过阴道镜检查与乙酰旋转的区域可以发现涉嫌发育不良的区域，但这是一种主观诊断，精度有限且可变性。该研究项目的目的是开发一个新颖的连贯成像平台，用于实际检测宫颈发育不良。达到这一目标将改善对疾病发展的诊断和理解。已经提出了许多用于检测子宫颈癌前病变的光学技术，但主要是由于性能有限，但尚未广泛采用。虽然高分辨率方法表现出良好的灵敏度，但需要手动扫描探针跨eCtiCervix限制效用。相比之下，广泛的成像方法检查了更多的组织区域，但表现出有限的特异性。在这里，我们建议使用多重模态方法创建一个成像平台，结合宽场成像，使用多路复用的低相干干涉仪（MLCI）进行全面的宫颈映射，并使用高分辨率，深度分辨的核形态测量，并使用高分辨率分辨的核形态测量。 （A/LCI）用于高度敏感的发育异常。这项研究的长期目标是创建多模式仪器，以诊断宫颈发育不良。提出了以下特定目标。 1）开发多重LCI用于映射子宫颈的上皮类型。 MLCI探针将进行外坐骨的大面积扫描，以绘制鳞状到柱状过渡区（T-Zone）。杜克大学的主要研究证明将验证MLCI探测器，然后在UCSF进行更广泛的研究。将数据与管道造影术进行比较，该术是评估T区的当前标准。 2）适应角度分辨的LCI检测宫颈发育不良。 A/LCI可以通过深度解决核形态测量的深度检测发育不良病变。最初的体内试验研究将使用现有原型进行，并将开发优化的仪器来扫描eTecovix，而无需重新定位探针。该仪器将用于杜克大学的原则研究证明，然后在UCSF进行更广泛的研究中进行验证。为了评估准确性，将将A/LCI核形态测量与共同注册的身体活检的组织病理学评估进行比较。 3）将MLCI和A/LCI集成到单个成像平台中。集成平台将使大型MLCI扫描能够映射子宫颈的T区，并作为A/LCI核形态测量的指南，以鉴定选定点的发育异常。该仪器将用于杜克大学的试点研究中，然后在UCSF的临床现场测试中应用。将将光学成像测量与数字人际摄影进行比较，以验证T区映射并共同注册的物理活检，以确认核形态与组织病理组织状态的比对。