Diagnosis of Ovarian Cancer by Confocal Microendoscopy

描述（由申请人提供）： 本研究的目的是开发一种用于卵巢癌早期检测的筛查工具，该工具能够使用微创手术入路诊断卵巢中的微观癌症或异常区域。卵巢癌在所有妇科疾病中死亡率最高，因为它通常在晚期被诊断出来，导致生存的总体预后不良。荧光共聚焦显微内窥镜是一种新型的用于在细胞水平上可视化组织的仪器，在进行光学活检方面显示出很大的前景。初步工作表明，该仪器在卵巢成像和识别病理方面具有重要潜力。共聚焦显微镜具有增强医生诊断能力的能力，并最终提供用于病理学的实时体内诊断的自动化图像分析工具。本论文的具体工作目标如下：1）建立一种能够在临床上常规使用的、可靠的第三代共焦显微内窥镜。该系统将是紧凑的，移动的，并纳入高灵敏度灰度和多光谱成像能力。2)建立一种可靠的外源性荧光造影剂局部给药机制。理想情况下，这将是一种非（或最小）接触技术，允许良好控制组织暴露于外源性试剂。3)将自动实时模式识别能力纳入系统。这种能力将有助于手术医生在卵巢表面连续成像期间识别病理。4)评价特定荧光化合物用作腹膜腔造影剂的安全性和有效性，该造影剂将局部递送至卵巢表面。这项工作将在啮齿动物模型中完成。5)验证该仪器用于人体卵巢活体成像的可行性。这将证明基本的系统概念是有效的，并指出需要解决的实际问题。6)目的：评价该仪器在卵巢病理检查中的临床应用价值。这将是一项更广泛的研究，以评估该技术在一系列组织学诊断（包括正常卵巢、良性肿瘤和癌症）中的灵敏度和特异性。临床评价将在计划接受卵巢切除术的女性队列中进行。

DESCRIPTION (provided by applicant): The objective of this research is to develop a screening tool for the early detection of ovarian cancer with the capability of diagnosing microscopic cancers or areas of abnormality in the ovary using minimally invasive surgical access. Ovarian cancer has the highest mortality of any of the gynecologic conditions because it is usually diagnosed in late stages leading to poor overall prognosis for survival. The fluorescence confocal microendoscope is a new type of instrument for visualizing tissue at the cellular level that has shown great promise for performing optical biopsy. Preliminary work suggests significant potential for this instrument in imaging and identifying pathology in the ovary. Confocal microscopy has the capability to enhance a physicians' diagnostic ability and ultimately provide an automated image analytic tool for real-time in vivo diagnosis of pathology. The specific aims of the work are as follows: 1) To build a third-generation confocal microendoscope instrument that can be used routinely and reliably in the clinic. The system will be compact, mobile, and incorporate high sensitivity grayscale and multi-spectral imaging capabilities. 2) To develop a reliable mechanism for localized delivery of exogenous fluorescence contrast agent. Ideally this will be a non- (or minimum) contact technique that will allow well-controlled exposure of tissue to the exogenous agents. 3) To incorporate automated real-time pattern recognition capability into the system. This capability will assist the operating physician in identifying pathology during continuous imaging of the surface of the ovary. 4) To evaluate the safety and efficacy of specific fluorescent compound(s) for use as contrast agents in the peritoneal cavity that will be delivered topically to the surface of the ovary. This work will be done in a rodent model. 5) To demonstrate the feasibility of using the instrument for in vivo imaging of human ovary. This will prove that the basic system concept works and to point out practical issues that need to be addressed. 6) To assess the efficacy of the clinical instrument for detection of pathology of the ovary. This will be a more extensive study to evaluate the sensitivity and specificity of this technique across a range of histologic diagnoses including normal ovary, benign neoplasms, and cancers. The clinical evaluations will be done in a cohort of women who are scheduled to undergo oophrectomy procedures.