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 发病率是IS是。 HIV阳性同性恋者中的高度高，每100,000个主要挑战。 诊断和预防是缺乏标准化的筛选程序。 明天的共聚焦显微镜和光学连贯性等技术有可能可视化 与肛门恶性肿瘤相关的细胞形态学变化，但它们的临床适应性一直是 在此开拓者R21项目中具有挑战性 可以帮助准确诊断肛门癌的显微镜（SLSM）设备，目的是最终还原 肛门癌相关的病态和死亡率。 现有的体内显微镜技术（例如，CM，OCT），同时实现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）低成本（〜$ 2,000）。 将在体内揭示关键的诊断细胞特征，该特征将促进早期肛门的检测 SLSM设备的恶性和及时开始。 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病态性和 并发症是由不必要的良性病变活检引起的。 开发原型手持式SLSM设备并评估诊断诊断诊断的准确性 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 将在上皮中提供细胞分辨率，并揭示单个较深区域的建筑细节 图像。我们将最佳设计照明和检测光学元件 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的轴向分辨率。 在AIM 2中，浅层层次是对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活检。 SLSM设备将与相应的组织学图像进行比较 在SLSM中可视化的建筑特征并开发SLSM诊断标准 SLSM的特异性将评估自动化图像分析 还将开发算法来定量评估细胞和结构特征 提供低成本显微镜工具工具工具有助于准确诊断肛门恶性肿瘤，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 对手术边缘的评估和核心针活检期间的质量分配。