Low-Cost, Handheld Light Sheet Microscope for Guiding Anal Cancer Diagnosis

用于指导肛门癌诊断的低成本手持式光片显微镜

• 批准号: 10382361
• 负责人: Dongkyun Kang
• 金额: $ 17.51万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382361
• 关键词: Address; Adoption; Algorithmic Analysis; Anus; Architecture; Benign; Biological Markers; Biopsy; Cellular Morphology; Cervical; Cervical Cancer Screening; Clinical; Clinical Research; Complication; Confocal Microscopy; Core Biopsy; Cytology; Cytoplasm; Detection; Devices; Diagnosis; Diagnostic; Early Diagnosis; Epithelial; Goals; Gold; HIV Seropositivity; Histology; Homosexuals; Image; Incidence; Lamina Propria; Lateral; Lesion; Light; Lighting; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Microscope; Microscopy; Morbidity - disease rate; Mucous Membrane; Needles; Nuclear; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Oral; Pain; Pap smear; Performance; Procedures; Program Appropriateness; Resolution; Scanning; Screening procedure; Sensitivity and Specificity; Severities; Signal Transduction; Skin; Skin Cancer; Source; Specificity; Standardization; Surgical margins; Technology; Thick; Time; Tissues; Visualization; accurate diagnosis; automated image analysis; base; cancer diagnosis; cancer prevention; cellular imaging; clinical application; cost; design; diagnostic accuracy; diagnostic criteria; feasibility testing; fluorescence imaging; histological image; human imaging; imaging capabilities; imaging probe; improved; in vivo; men; microscopic imaging; mortality; prototype; quality assurance; screening program; tool; tumor

Project Summary/Abstract Anal cancer incidence has been increasing, by four times over the last three decades. The incidence rate is unacceptably high among HIV-positive homosexual men, 131 per 100,000. The main challenge in anal cancer diagnosis and prevention is the lack of a standardized screening program. In vivo optical microscopy technologies such as confocal microscopy and optical coherence tomography have the potential to visualize cellular morphologic changes associated with the anal malignancy, but their clinical adaptation has been challenging. In this Trailblazer R21 project, we propose to develop a low-cost, scattering-based light sheet microscopy (sLSM) device that can aid accurate diagnosis of anal cancer, with the goal of ultimately reducing the anal cancer-associated morbidity and mortality. Our sLSM device will uniquely address the unmet needs in existing in vivo microscopy technologies (e.g., CM, OCT), simultaneously achieving i) high lateral resolution (1- 2 µm) for examining cellular nuclear features in the epithelium, ii) large FOV (~2.5 mm), iii) visualization of the entire epithelial thickness in a single image, and iv) low device cost (~$2,000). We expect that the sLSM device will reveal the key diagnostic cellular features in vivo, which will facilitate detection of early-stage anal malignancy and timely initiation of adequate treatment. The sLSM device will also guide the biopsy to malignant lesions with high sensitivity and specificity to increase the biopsy yield and reduce the morbidity and complication caused by the unnecessary biopsy of benign lesions. As the first step towards this goal, we will develop the prototype handheld sLSM device and evaluate the accuracy of diagnosing anal malignancy in the following aims: In Aim 1, we will develop a handheld sLSM probe for imaging anal mucosa. The sLSM device will provide cellular resolution in the epithelium and reveal architectural details in deeper regions in a single image. We will optimally design the illumination and detection optics to achieve the 1.4 µm lateral resolution over a 2.5-mm FOV, 6.5 ± 0.9 µm axial resolution for the epithelium, and 18 ± 8 µm axial resolution for the superficial lamina propria. In Aim 2, we will conduct a clinical study of imaging human anal tissues with the handheld sLSM device. One hundred anal biopsies concerning for anal cancer will be first imaged with the sLSM device. sLSM images will be compared with the corresponding histologic images to identify cellular and architectural features visualized in sLSM images and to develop the sLSM diagnostic criteria. The sensitivity and specificity of the sLSM for diagnosing anal malignancy will be evaluated. Automated image analysis algorithms will be developed to quantitatively evaluate the cellular and architectural features. In addition to providing a low-cost microscopy tool that aids accurate diagnosis of anal malignancy, the sLSM technology can be used for in vivo diagnosis of other cancers (e.g., cervical, oral, skin cancers), intra-operative assessment of the surgical margin, and quality assurance during the core needle biopsy.

项目摘要/摘要 在过去的三十年中，肛门癌的事件一直在增加四倍。事件率是 在艾滋病毒阳性同性恋男性中，高度高，每100,000人131。肛门癌的主要挑战 诊断和预防是缺乏标准化的筛选程序。体内光学显微镜 共聚焦显微镜和光学相干断层扫描等技术具有可视化的潜力 与肛门恶性肿瘤相关的细胞形态变化，但它们的临床适应性一直是 挑战。在此开拓者R21项目中，我们建议开发低成本的基于散射的光片 可以帮助准确诊断肛门癌的显微镜（SLSM）设备，目的是最终降低 肛门癌相关的发病率和死亡率。我们的SLSM设备将唯一满足未满足的需求 现有的体内显微镜技术（例如，CM，OCT），易于实现i）高横向分辨率（1- 2 µm）用于检查上皮中的细胞核特征，ii）大型FOV（〜2.5 mm），iii）可视化 单个图像中的整个上皮厚度，iv）低设备成本（约$ 2,000）。我们希望SLSM设备 将在体内揭示关键的诊断细胞特征，这将有助于检测早期肛门 恶性和及时开始适当治疗。 SLSM设备还将引导活检 具有高灵敏度和特异性的恶性病变，以增加活检产量并降低发病率和 并发症是由不必要的良性病变活检引起的。作为朝着这个目标的第一步，我们将 开发原型手持式SLSM设备并评估诊断肛门恶性肿瘤的准确性 以下目的：在AIM 1中，我们将开发用于成像肛门粘膜的手持式SLSM探针。 SLSM设备 将在上皮提供细胞分辨率，并在一个更深层次的区域中揭示了建筑细节 图像。我们将最佳设计照明和检测光学元件以实现1.4 µm的横向分辨率 在2.5毫米的FOV上，上皮的6.5±0.9 µm轴向分辨率和18±8 µm轴向分辨率 浅层层。在AIM 2中，我们将对成像人类肛门组织进行成像的临床研究 手持式SLSM设备。有关肛门癌的一百个肛门单曲将首先成像 SLSM设备。 SLSM图像将与相应的组织学图像进行比较，以识别细胞和 在SLSM图像中可视化并制定SLSM诊断标准。灵敏度 将评估SLSM的SLSM特异性。自动图像分析 将开发算法以定量评估细胞和结构特征。此外 提供一个低成本显微镜工具，可帮助准确的肛门恶性肿瘤诊断，SLSM技术 可用于其他癌症的体内诊断（例如宫颈，口服，皮肤癌），术中术 评估手术边缘和核心针活检期间的质量保证。