Towards In Situ Optical Pathology of Nonmelanoma Skin Cancers

描述（由申请人提供）：非黑色素瘤皮肤癌是人类癌症中最常见的形式。因此，迫切需要高分辨率检测和显微镜控制下切除这些肿瘤。目前，病理学家使用低功率显微镜观察肿瘤边缘，并在高功率下检查细胞特征，以诊断和管理非黑色素瘤皮肤癌。我们建议开发一种多模式设备，使宽视场和高分辨率成像在体内和真实的时间。该设备将结合联合收割机的能力，CCD宏观成像，使快速检查的表面组织层在大的表面，共聚焦显微镜，允许成像混浊介质的分辨率与组织学。仪器将在这些模式之间缩放，允许更宽的视图引导高分辨率视图。两种模式都将采集反射、荧光和荧光偏振图像。为了增强所获取图像的对比度，我们将使用FDA批准的低浓度无毒的常规组织学染色剂，即亚甲基蓝，来模拟H&E组织病理学的染色模式。该技术的可行性将通过体外和体内试点试验与切除的人类非黑色素瘤皮肤癌标本和小动物，分别探讨。在技术开发阶段，将进行三项试点试验。第一个试验与切除的非黑色素瘤皮肤癌标本的目的是确定诊断功能的光学图像相比，组织学。在第二次试验的过程中，第一阶段定义的诊断标准将用于临床试验，届时该系统将用于对人类非黑色素瘤皮肤癌进行莫氏显微切除术期间的开放手术野进行成像。最后，将在小动物中测试所开发技术的诊断能力，方法是对疑似鳞状细胞癌的病变进行成像，并根据组织病理学分析将结果与诊断结果进行比较。在该项目过程中开发的非侵入性设备和方法将能够原位识别肿瘤边缘和小肿瘤巢，从而改善癌症治疗的结果。该技术的诊断应用有可能取代活检，从而减少与侵入性手术相关的发病率和时间。

DESCRIPTION (provided by applicant): Nonmelanoma skin cancer is the most common form of human cancer. Therefore, there is a strong need for high-resolution detection and microscopically controlled removal of these neoplasms. Currently pathologists use microscopes at low power to view tumor margins and at high power to inspect cell features for diagnosis and management of nonmelanoma skin cancers. We propose to develop a multimodal device that will enable both wide-field and high-resolution imaging in vivo and in real time. The device will combine the capabilities of the CCD macro-imaging that enables rapid inspection of a superficial tissue layer over large surfaces, and confocal microscopy that allows imaging within turbid media with resolution comparable to that of histology. The instrument will zoom between these modes, allowing the wider view to direct the high resolution view. Both modes will acquire images in reflectance, fluorescence, and fluorescence polarization. To enhance the contrast of the acquired images, we will use an FDA-approved conventional histological stain, non-toxic at low concentrations, i.e. Methylene Blue, to mimic the staining pattern of H&E histopathology. The feasibility of the technology will be explored by in vitro and in vivo pilot trials with excised human nonmelanoma skin cancer specimens and in small animals, respectively. During the technology development stage three pilot trials will be conducted. The first trial with excised nonmelanoma skin cancer specimens is designed for determining diagnostic features in optical images by comparison to histology. In the course of the second trial, the diagnostic criteria defined by the first stage will be used in a clinical trial, when the system will be employed for imaging open surgical fields during Mohs micrographic removal of nonmelanoma skin cancers in humans. Finally, the diagnostic capability of the developed technology will be tested in small animals by imaging lesions suspicious for squamous cell carcinoma and comparing the results to the diagnosis, based on the analysis of histopathology. The noninvasive device and methods developed in the course of this project will enable identification of tumor margins and small tumor nests in situ, leading to improved outcomes of cancer treatments. The diagnostic application of this technology holds the potential to replace biopsy, thus reducing morbidity and time associated with that invasive procedure.