Structured chromatic light sheet microscopy

摘要 该项目的长期目标是开发一种紧凑、无标签、低成本的上皮成像光学设备 组织在癌症检测和诊断中的作用。80%-90%的癌症发生在上皮组织中。五花八门 已经开发了用于早期检测和诊断的高分辨率光学成像技术和设备 上皮性疾病，但大多数是复杂和昂贵的，不适合在护理点应用 低资源配置环境。 我们建议开发一种结构色光薄片显微镜。关键的创新是使用了白色的 µLED阵列产生结构色光薄片，不需要外部笨重的光源和 扫描仪或空间光调制器，以获得3D组织图像。另一项关键的创新是色度法 基于线性可变滤光片的狭缝共焦检测 对比度和分辨率。通过拍摄和处理，图像的分辨率和对比度将进一步提高 用相移结构光调制的三幅图像。还预计图像分辨率和 通过聚焦和成像更深层次的长波长光片，可以改善更深层次的对比度 纸巾。此外，还可以通过顺序投影结构光片来获得体积图像 通过焦平面与2D微米LED阵列。 在这个项目中，我们将首先开发一台结构色光薄片显微镜(目标1)，然后评估 原型机结构彩色光片显微镜在上皮组织成像中的性能(目标2)。 利用在目标1和目标2中获得的知识，我们还将开发和评估手持结构化彩色图像 用于上皮组织成像的光片显微镜(目标3)。 彩色光片和彩色狭缝共焦探测的概念将对光产生深远的影响 散射成像及其在上皮性癌检测和诊断中的潜在应用。这个项目将 为早期发现皮肤癌和口腔癌提供了一种有效的临床工具，这将大大减少 减少疾病进展和死亡率，提高生活质量。此外，这个负担得起的工具将非常实用 用于低资源环境，以减轻低收入和中等收入国家的皮肤癌和口腔癌负担 (LMIC)。此外，拟议的显微镜可以改进活检点的定位和描绘 手术切缘减少，这将减少重复和随机活检的需要。

Abstract The long-term goal of this project is to develop a compact, label-free, low-cost optical device for imaging epithelial tissues in cancer detection and diagnosis. 80-90% cancers arise as carcinomas in epithelial tissues. Various high resolution optical imaging techniques and devices have been developed for early detection and diagnosis of epithelial diseases, but most of them are complicated and expensive, not suitable for point-of-care applications and low resource setting environment. We propose to develop a structured chromatic light sheet microscope. The key innovation is the use of a white µLED array to generate structured chromatic light sheet, eliminating the need of external bulky light source and scanner or spatial light modulator to obtain 3D tissue image. Another key innovation is the method of chromatic slit confocal detection using a linear variable filter to block the out-of-the-light-sheet light to improve image contrast and resolution. The image resolution and contrast will be further improved by taking and processing three images modulated with phase-shifted structured light. It is also expected that the image resolution and contrast in deeper layers can be improved by focusing and imaging a long wavelength light sheet deeper into the tissue. In addition, volumetric image can be obtained by projecting structured light sheets sequentially through the focal plane with 2D µLED array. In this project, we will first develop a structured chromatic light sheet microscope (Aim 1), and then evaluate the performance of the prototyped structured chromatic light sheet microscope in imaging epithelial tissue (Aim 2). With the knowledge gained in Aims 1 and 2, we will also develop and evaluate a handheld structured chromatic light sheet microscope for epithelial tissue imaging (Aim 3). The concepts of chromatic light sheet and chromatic slit confocal detection will have profound impact on light scattering imaging and potential applications in detection and diagnosis of epithelial cancers. This project will result in an effective clinical tool for early detection of skin and oral cancers, which will significantly reduce disease progression and mortality and improve quality of life. Further, this affordable tool will be very practical for low-resource settings to reduce the burden of skin and oral cancers in low- and middle- income countries (LMICs). In addition, the proposed microscope could enable improved localization of biopsy sites and delineation of surgical margins, which will reduce the need for repeat and random biopsies.