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）：宫颈癌是美国发病的一个重要原因，每年约有 12,200 例新病例和 4,200 人死于该疾病。作为一种筛查工具，宫颈细胞学检查（巴氏涂片）可以通过检测癌前病变来降低发病率；但它无法定位宫颈发育不良区域，而这是活检指导和治疗所必需的。目前，怀疑发育不良的区域是通过阴道镜检查和醋酸美白来发现的，但这是一种主观诊断，准确性有限且变异性很大。该研究项目的目标是开发一种新型相干成像平台，用于实际检测宫颈发育不良。实现这一目标将改善对疾病发展的诊断和理解。已经提出了许多光学技术来检测子宫颈癌前病变，但由于性能有限，尚未得到广泛采用。虽然高分辨率方法显示出良好的灵敏度，但需要手动扫描子宫颈阴道部的探针限制了实用性。相比之下，广域成像方法检查更多的组织区域，但特异性有限。在这里，我们建议创建一个基于多模态方法的成像平台，结合宽视场成像，使用多路复用低相干干涉测量（mLCI）进行全面的宫颈测绘，与高分辨率、深度分辨核形态测量，使用角度分辨LCI (a/LCI) 用于高度灵敏地检测不典型增生。这项研究的长期目标是创建多模式仪器来诊断宫颈发育不良。提出以下具体目标。 1) 开发多重 LCI 来绘制宫颈上皮类型。 mLCI 探头将对子宫颈阴道部进行大面积扫描，以绘制鳞状到柱状过渡区（T 区）的图。杜克大学的原理证明研究将验证 mLCI 探针，随后加州大学旧金山分校将进行更广泛的研究。数据将与阴道摄影术（目前评估 T 区的标准）进行比较。 2) 采用角度分辨 LCI 来检测宫颈发育不良。 a/LCI 可以通过深度分辨核形态测量来检测发育异常病变。将使用现有原型进行初步体内试点研究，并将开发优化的仪器来扫描宫颈外口，而无需重新定位探头。该仪器将用于杜克大学的原理证明研究，然后在加州大学旧金山分校的更广泛研究中进行验证。为了评估准确性，a/LCI 核形态测量将与共同注册的物理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。该集成平台将实现大面积 mLCI 扫描，绘制宫颈 T 区图，并作为 a/LCI 核形态测量的指南，以识别选定点的发育不良。该仪器将用于杜克大学的试点研究，然后应用于加州大学旧金山分校的临床现场测试。光学成像测量结果将与数字阴道照相术进行比较，以验证 T 区映射，并与共同配准的物理活检进行比较，以确认核形态与组织病理学组织状态的一致性。