Rogalla Stephan, Contag Christopher H
From the *Division of Neonatology, Department of Pediatrics, Stanford University, Stanford, CA; and †Molecular Imaging Program at Stanford (MIPS), Stanford University, Departments of Pediatrics, Radiology, and Microbiology & Immunology, Stanford University, Clark Center E150, 318 Campus Drive, Stanford, CA.
Cancer J. 2015 May-Jun;21(3):179-87. doi: 10.1097/PPO.0000000000000122.
Malignant neoplastic lesions derived from epithelial tissue, carcinomas, account for 80% to 100% of all human cancers including some of the most deadly diseases such as cervical and non-small cell lung cancer. Many of these carcinomas present at readily accessible epithelial surfaces offering unique detection opportunities. Effective clinical management of carcinomas is enabled by early detection, at a time when full surgical resection is possible and before invasion of adjacent tissue or significant intravasation into blood vessels leading to metastasis. Good prognosis with long-term disease-free survival is more likely after early detection when progression is limited. At present, detection of carcinomas at epithelial surfaces largely relies on routine inspection with the naked eye (e.g., skin and oropharynx) or simple white light tools (e.g., cervix and colon). Emerging optical tools based on differential refraction, absorption, reflection, scattering, or fluorescence of carcinomas relative to normal tissues enable label-free visualization of neoplasia. However, the differences in intrinsic optical properties of normal and malignant tissues can be subtle, and relying on these may lead to high miss rates. Enhanced optical contrast offered by molecularly targeted agents can be used to improve early detection; and given that optical imaging and sensing tools can be readily combined, integrated systems that image over a range of scales, or detect multiple parameters, can be developed to aid in early detection. Diagnosis is, at present, made by histologic examination of tissue biopsies after identification of suspicious lesions. Miniature and handheld microscopic imaging tools have recently been developed, and integration of these tools with wide-field optical surveillance devices offers both rapid detection and confirmatory histologic examination at the point-of-care, that can provide guidance for biopsy and/or resection. A wide variety of targeted probe strategies have been described with demonstrated benefit in preclinical models and in a limited number of human studies. Here, we present examples of integrated multimodality optical imaging and sensing tools that use combinations of intrinsic and extrinsic optical contrast for early detection or margin delineation for carcinomas at epithelial surfaces. We will discuss several new technologies that have use in detecting the most common carcinomas that derive from the epithelium of the skin, gastrointestinal and urogenital tracts, and bronchoalveoli.
源自上皮组织的恶性肿瘤性病变，即癌，占所有人类癌症的80%至100%，包括一些最致命的疾病，如宫颈癌和非小细胞肺癌。这些癌中的许多出现在易于触及的上皮表面，提供了独特的检测机会。癌的有效临床管理可通过早期检测实现，此时有可能进行完整的手术切除，且在邻近组织受侵或大量血管内播散导致转移之前。早期检测且进展有限时，更有可能实现长期无病生存的良好预后。目前，上皮表面癌的检测很大程度上依赖于肉眼常规检查（如皮肤和口咽）或简单的白光工具（如宫颈和结肠）。基于癌与正常组织的微分折射、吸收、反射、散射或荧光的新兴光学工具能够实现肿瘤的无标记可视化。然而，正常组织和恶性组织的固有光学特性差异可能很细微，仅依赖这些特性可能导致高漏诊率。分子靶向剂提供的增强光学对比度可用于改善早期检测；鉴于光学成像和传感工具可轻松组合，可开发在一系列尺度上成像或检测多个参数的集成系统，以辅助早期检测。目前，在识别可疑病变后，通过组织活检的组织学检查进行诊断。最近已开发出微型和手持式显微成像工具，将这些工具与宽视野光学监测设备集成，可在护理点实现快速检测和确诊组织学检查，为活检和/或切除提供指导。已经描述了多种靶向探针策略，在临床前模型和有限数量的人体研究中显示出益处。在此，我们展示了集成多模态光学成像和传感工具的实例，这些工具利用固有和外在光学对比度的组合，用于上皮表面癌的早期检测或边缘勾勒。我们将讨论几种可用于检测源自皮肤、胃肠道、泌尿生殖道和支气管肺泡上皮的最常见癌的新技术。
