Rapid 3D Whole-Slide Digitization of Thick Cytopathology Slides with a Gigapixel Microscope

使用十亿像素显微镜对厚细胞病理学载玻片进行快速 3D 全载玻片数字化

• 批准号: 10010727
• 负责人: Mark Harfouche
• 金额: $ 40万
• 依托单位: RAMONA OPTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10010727
• 关键词: 3-Dimensional; Academic Medical Centers; Archives; Area; Biological Sciences; Biopsy; Bone Marrow Aspiration; Clinical; Collaborations; Computer software; Consumption; Custom; Cytology; Cytopathology; Data; Data Set; Development; Devices; Diagnosis; Diagnostic; Effectiveness; Evaluation; Feedback; Fine needle aspiration biopsy; Fluorescence; Gastrointestinal tract structure; Gold; Hospitals; Image; Image-Guided Surgery; Imagery; Lateral; Light Microscope; Lighting; Location; Lung; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of thyroid; Measurement; Measures; Microscope; Modality; Molecular; Needles; Optics; Pathologist; Pathology; Patient Care; Performance; Persons; Phase; Procedures; Process; Repeat Surgery; Resolution; Robotics; Sales; Sampling; Scanning; Site; Slide; Specimen; Speed; Surgical Pathology; System; Technology; Testing; Thick; Three-Dimensional Image; Thyroid Gland; Time; Universities; Visual; Work; base; cancer diagnosis; clinical application; clinically relevant; computerized data processing; design; diagnostic accuracy; digital; digital imaging; digital pathology; experimental study; gigabyte; improved; lens; performance tests; processing speed; screening; tool; whole slide imaging; 3-Dimensional; Academic Medical Centers; Archives; Area; Biological Sciences; Biopsy; Bone Marrow Aspiration; Clinical; Collaborations; Computer software; Consumption; Custom; Cytology; Cytopathology; Data; Data Set; Development; Devices; Diagnosis; Diagnostic; Effectiveness; Evaluation; Feedback; Fine needle aspiration biopsy; Fluorescence; Gastrointestinal tract structure; Gold; Hospitals; Image; Image-Guided Surgery; Imagery; Lateral; Light Microscope; Lighting; Location; Lung; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of thyroid; Measurement; Measures; Microscope; Modality; Molecular; Needles; Optics; Pathologist; Pathology; Patient Care; Performance; Persons; Phase; Procedures; Process; Repeat Surgery; Resolution; Robotics; Sales; Sampling; Scanning; Site; Slide; Specimen; Speed; Surgical Pathology; System; Technology; Testing; Thick; Three-Dimensional Image; Thyroid Gland; Time; Universities; Visual; Work; base; cancer diagnosis; clinical application; clinically relevant; computerized data processing; design; diagnostic accuracy; digital; digital imaging; digital pathology; experimental study; gigabyte; improved; lens; performance tests; processing speed; screening; tool; whole slide imaging

Significance: Digital microscopes are becoming an indispensable tool within the pathology lab. Whole-slide microscope scanners are now routinely used to record gigapixel-sized images of surgical pathology specimens for archival, sharing, annotation and automated processing. Unfortunately, whole-slide scanners still cannot efficiently digitize thick specimens, such as fine-needle aspirates (FNAs) and other cytology samples that are commonly used as the first-line modality for diagnosing cancer of the lung, thyroid, pancreas and other sites. Standard microscope lenses can only capture data from a 1 mm2 area per snapshot. Given this limitation, it is currently not technically feasible to fully scan out an entire slide in 3D, which leads to a number of critical bottlenecks within the cytologist's workflow for cancer diagnosis. Proposal: Ramona Optics is developing a new micro-camera array microscope (MCAM) that can overcome these limitations to digitize thick specimens (up to 50 µm deep) at 1 µm3 volumetric resolution across an entire slide. The resulting multi-gigabyte recording can then be examined by cytopathologists via a custom-developed 3D software interface to aid with various diagnostic tasks. In Phase I of this Fast-Track proposal, Ramona will finalize the hardware and software for its new MCAM-3D device. In Phase II, Ramona will collaborate with the Duke University Medical Center and several other cytopathologists to test and measure MCAM-3D performance on several relevant clinical tasks, including remote telecytology-based assessment of FNA sample adequacy, as well as suitability for secondary diagnosis. Apart from improving workflow and patient care in the hospital, Ramona Optics also expects the MCAM- 3D to enable a number of critical high-throughput imaging experiments in the life sciences that are currently not possible due to the limited throughput of current standard microscope designs. SA1 (Phase I): Integrate hardware and software for whole-slide MCAM-3D capture: Ramona will complete development of an MCAM-3D device that digitizes whole slides (12 cm2 area, 50 µm thick) at 0.8 and 2.6 µm/pixel lateral and axial resolution within 1.5 minutes. 3D viewing software will enable real-time interaction with the multi-gigabyte recorded data volume, offering ~50X more measurements than current 2D whole-slide scanners. SA2 (Phase II): Evaluate MCAM-3D for telecytology and improve system specifications: In collaboration with 3 cytopathologists at the Duke University Medical Center, Ramona will test the MCAM-3D for remote rapid on-site evaluation (ROSE) of sample adequacy. ROSE is well-known to improve patient care by reducing repeat procedures. The objective of this aim is to show that the MCAM-3D can make ROSE easier, quicker and potentially more accurate. At the same time, Ramona will incorporate study findings to improve lateral/axial imaging resolution to 0.5 µm/1 µm and scanning speed to 30 sec. SA3 (Phase II): 3D whole-slide digitization and remote viewing for clinical applications: Ramona will improve the MCAM-3D's processing speeds to enable real-time remote viewing of 3D samples within the Duke University Medical Center. It will then work with cytopathologists to carefully assess its performance at telecytology-based diagnoses and archiving specimen material as it works towards a finalized product for sale 6 months after the conclusion of this project.

意义：数字显微镜已成为病理实验室中必不可少的工具。全滑动显微镜 现在，扫描仪通常用于记录用于档案，共享，共享的手术病理标本的千兆像素大小的图像 注释和自动处理。不幸的是，全滑动扫描仪仍无法有效地数字化厚标本，例如 作为精细的抽吸物（FNA）和其他通常用作诊断第一线形态的细胞学样本 肺癌，甲状腺，胰腺和其他部位。标准显微镜镜头只能捕获每个1 mm2面积的数据 快照。鉴于此限制，目前在技术上不可行，可以在3D中进行全面扫描，这导致了一个 细胞学家工作流程中的关键瓶颈数量用于癌症诊断。提案：Ramona Optics正在开发 可以克服这些限制以数字化厚标本的新微型摄像机阵列显微镜（MCAM）（高达50 µm） 深）在整个载玻片上以1 µm3的体积分辨率。然后可以通过 细胞病理学家通过自定义开发的3D软件接口，以帮助完成各种诊断任务。在此快速轨道的第一阶段 提案，Ramona将为其新的MCAM-3D设备最终确定硬件和软件。在第二阶段，拉莫纳将合作 与杜克大学医学中心和其他几位细胞病理学家一起测试和测量MCAM-3D的性能 几项相关的临床任务，包括基于远程电信的FNA样本是否适当评估，以及适合于 次要诊断。除了改善医院的工作流程和患者护理外，Ramona Optics还期望MCAM- 3D可以在生命科学中进行许多关键的高通量成像实验 对于当前标准显微镜设计的有限吞吐量。 SA1（I阶段）：整合硬件和软件，用于全扫描MCAM-3D捕获：Ramona将完成 在0.8和2.6 µm/像素的横向和 轴向分辨率在1.5分钟内。 3D查看软件将启用与多gabyte记录的数据实时互动 体积，提供约50倍的测量值，比当前的2D全滑动扫描仪多。 SA2（II阶段）：评估MCAM-3D电信和改进系统规格：与3合作 Ramona杜克大学医学中心的细胞病理学家将测试MCAM-3D的远程快速现场评估 （玫瑰）的样本充足性。玫瑰是众所周知的，可以通过减少重复程序来改善患者护理。这个目的 目的是证明MCAM-3D可以使玫瑰更轻松，更快且可能更准确。同时，拉莫纳 将结合研究结果，以将横向/轴向成像分辨率提高到0.5 µm/1 µm，并扫描速度至30秒。 SA3（II阶段）：3D全面数字化和临床应用的远程查看：Ramona将有所改善 MCAM-3D的处理速度可实时远程查看杜克大学医疗中的3D样品 中心。然后，它将与细胞病理学家一起仔细评估其在基于电信的诊断和存档中的表现 该项目结束后6个月，标本材料用于最终产品出售的最终产品。