Confocal line-scanning versus point-scanning for imaging human skin in vivo

描述（由申请人提供）：本项目的目标是比较两个共焦线扫描显微镜的标准共焦点扫描显微镜的人体皮肤在体内的反射成像。一个行扫描器是基于一个分开的物镜透镜瞳孔和其他基于一个完整的瞳孔配置。每种配置都有优点。长期目标是创建一个从根本上更简单的类共焦反射扫描显微镜成像人类皮肤癌的临床和外科皮肤病学。每年，仅在美国，就有120万新的皮肤癌病例被诊断出来。在进行的550万次活检中，80%是正常的，因此是可以避免的，每年花费美国医疗保健16.5亿美元。共焦反射显微镜可以使这些皮肤癌的非侵入性和实时的筛查和诊断，活检的需要最小。假设是具有分光瞳或全光瞳的共焦线扫描仪将是简单的，并且将提供非常高的分辨率和光学切片。这种线扫描显微镜可以与当今最先进的点扫描显微镜竞争，用于人体皮肤活体成像，用于临床诊断和手术指导应用。初步结果与原型共焦分光瞳线扫描仪展示了核和细胞的细节在人体皮肤的表皮在体内成像。原型比点扫描仪简单得多。具体目标是创建一个共焦线扫描仪，结合了分光瞳和全光瞳配置。组合的分割和完整的瞳孔将使其线扩散函数（LSF）和成像性能在相同的光学和皮肤条件下的实验评估。实验比较了分光瞳和全光瞳LSF的共焦点扩散函数（PSF）将在两个条件下：衍射限制（即）。例如，标称仪器）条件以及实际皮肤的散射和畸变条件（即，例如，深入人真皮，穿过全层表皮）。分光瞳和全瞳孔线扫描图像的人的皮肤，无论是在体内和体外，将进行比较，组织学和共聚焦点扫描仪获得的良好表征的图像。将定量比较两种线扫描和点扫描方法的图像背景噪声和对比度。与公共卫生的相关性共焦反射显微镜可以筛查和诊断皮肤癌，如黑色素瘤和基底细胞癌和鳞状细胞癌，或者可以直接和实时地指导对患者进行此类癌症的手术。诊断或手术引导可以是非侵入性的，具有最小的活检需要、最小的疼痛和最小的费用。

DESCRIPTION (provided by applicant): The goal of this project is to compare two confocal line-scanning microscopes to a standard confocal pointscanning microscope for reflectance imaging of human skin in vivo. One line-scanner is based on a divided objective lens pupil and the other based on a full pupil configuration. Each configuration has advantages. The long-term objective is to create a fundamentally simpler class of confocal reflectance scanning microscopes for imaging human skin cancers for clinical and surgical dermatology. Every year, in the USA alone, 1.2 million new cases of skin cancers are diagnosed. Of the 5.5 million biopsies performed, 80% turn out to be normal and thus avoidable, costing US healthcare $1.65 billion annually. Confocal reflectance microscopy may enable screening and diagnosis of these skin cancers noninvasively and in real-time, with minimal need for biopsy. The hypothesis is that a confocal line-scanner with either a divided-pupil or a full pupil will be simple, and will provide very high resolution and optical sectioning. Such line-scanning microscopes may compete with today's state-of-the-art point-scanning microscopes for imaging human skin in vivo, for clinical diagnosis and surgical guidance applications. Preliminary results with a prototype confocal divided-pupil line-scanner demonstrate imaging of nuclear and cellular detail in the epidermis of human skin in vivo. The prototype is considerably less complicated than a point-scanner. The specific aims are to create a confocal line-scanner that combines both divided-pupil and full-pupil configurations. The combined divided-and-full pupil will enable experimental evaluation of their line spread functions (LSFs) and imaging performance under identical optical and skin conditions. Experimental comparisons of divided pupil and full-pupil LSFs to the confocal point spread function (PSF) will be made under two conditions: diffraction-limited (i. e., nominal instrument) conditions as well as scattering and aberrating conditions of actual skin (i. e., deep within human dermis, through full-thickness epidermis). Divided-pupil and full-pupil line-scanned images of human skin, both ex vivo and in vivo, will be compared to histology and to the well characterized images obtained by confocal point-scanners. Background noise and contrast in the images will be quantitatively compared between the two line-scanning and the point-scanning methods. RELEVANCE TO PUBLIC HEALTH Confocal reflectance microscopy may enable screening and diagnosis of skin cancers such as melanomas and basal- and squamous-cell carcinomas, or may guide surgery of such cancers, directly and in real-time on the patient. The diagnosis or surgical guidance may be noninvasive, with minimal need for biopsy, minimal pain and minimal expense.