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

意义：数字显微镜正在成为病理实验室中不可或缺的工具。全载玻片显微镜 扫描仪现在被常规地用于记录外科病理标本的千兆像素大小的图像以用于存档、共享、 注释和自动处理。不幸的是，全载玻片扫描仪仍然不能有效地数字化厚标本，如 作为细针抽吸物(FNAs)和其他细胞学样本，通常用作诊断的一线手段 肺癌、甲状腺癌、胰腺癌等部位。标准显微镜镜头只能捕捉1平方毫米范围内的数据。 快照。考虑到这一限制，目前在3D模式下完全扫描整个幻灯片在技术上是不可行的，这导致 细胞学家用于癌症诊断的工作流程中的关键瓶颈数量。建议：Ramona Optics正在开发一种 新的微相机阵列显微镜(MCAM)可以克服这些限制，实现厚样品(高达50微米)的数字化 深度)，整个幻灯片的体积分辨率为1微米。然后，可以通过以下方式检查所产生的多GB记录 细胞病理学家通过定制开发的3D软件界面帮助完成各种诊断任务。在此快速通道的第一阶段 根据提案，Ramona将最终敲定其新的MCAM-3D设备的硬件和软件。在第二阶段，雷蒙娜将合作 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，包括基于远程远程细胞学的FNA样本充分性评估，以及是否适合 二次诊断。除了改善医院的工作流程和患者护理外，Ramona Optics还希望MCAM- 3D使生命科学中的一些关键的高通量成像实验成为可能，因为 到目前标准显微镜设计的有限吞吐量。 SA1(第一阶段)：集成整个幻灯片的硬件和软件-MCAM-3D捕获：Ramona将完成 开发一种MCAM-3D设备，将整个幻灯片(面积12平方厘米，厚50微米)以0.8和2.6微米/像素的横向和横向数字化 1.5分钟内轴向分辨率。3D查看软件将实现与数十亿字节记录数据的实时交互 体积，提供比目前的2D全幻灯片扫描仪多约50倍的测量值。 SA2(第二阶段)：为电视细胞学评估MCAM-3D并改进系统规格：与3 雷蒙纳杜克大学医学中心的细胞病理学家将测试MCAM-3D以进行远程快速现场评估 (玫瑰)样本充分性。众所周知，ROSE通过减少重复手术来改善患者护理。这样做的目的是 目的是展示MCAM-3D可以使ROSE更容易、更快，而且可能更准确。与此同时，雷蒙娜 将结合研究成果，将横向/轴向成像分辨率提高到0.5微米/1微米，扫描速度提高到30秒。 SA3(第二阶段)：临床应用的3D全幻灯片数字化和远程查看：Ramona将得到改善 MCAM-3D的处理速度可实现实时远程查看杜克大学医学院内的3D样本 中心。然后，它将与细胞病理学家合作，仔细评估其在基于远程细胞学的诊断和归档方面的表现 在本项目结束后6个月，样品材料正朝着最终产品的方向发展。

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.