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学实验室中不可或缺的工具。全载玻片显微镜 扫描仪现在通常用于记录外科病理学样本的千兆像素大小的图像，用于存档，共享， 注释和自动化处理。不幸的是，全载玻片扫描仪仍然不能有效地扫描厚标本，例如 作为细针穿刺（FNA）和其他细胞学样本，通常用作诊断的一线模式 肺癌、甲状腺癌、胰腺癌和其他部位的癌症。标准的显微镜镜头只能从每平方毫米的面积上捕获数据。 snapshot.考虑到这种限制，目前在技术上不可行的是以3D完全扫描出整个载玻片，这导致 细胞学家的癌症诊断工作流程中的许多关键瓶颈。建议：Ramona Optics正在开发一种 新型微型相机阵列显微镜（MCAM）可以克服这些限制，对厚样本（高达50 µm）进行数字化 深度），1 µm3的体积分辨率。由此产生的多千兆字节的记录，然后可以检查， 细胞病理学家通过定制开发的3D软件界面，以帮助各种诊断任务。在此快速通道的第一阶段， 根据该提案，Ramona将最终确定其新MCAM-3D设备的硬件和软件。在第二阶段，雷蒙娜将与 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在 几个相关的临床任务，包括FNA样本充足性的远程评估，以及 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，这些实验目前由于 到当前标准显微镜设计的有限吞吐量。 SA 1（第一阶段）：整合硬件和软件，用于全切片MCAM-3D采集：Ramona将完成 开发MCAM-3D设备，以0.8和2.6 µm/像素横向数字化整个载玻片（12 cm 2面积，50 µm厚）， 轴向分辨率在1.5分钟内。3D观看软件将实现与多千兆字节记录数据的实时交互 体积，提供比当前2D全载玻片扫描仪多约50倍的测量。 SA 2（第二阶段）：评估MCAM-3D用于远细胞学并改进系统规格：与3 Ramona杜克大学医学中心的细胞病理学家将对MCAM-3D进行远程快速现场评估 （ROSE）样本充足性。众所周知，ROSE通过减少重复手术来改善患者护理。的目的 目的是表明MCAM-3D可以使ROSE更容易，更快，并可能更准确。与此同时，Ramona 将结合研究结果，将横向/轴向成像分辨率提高到0.5 µm/1 µm，扫描速度提高到30秒。 SA 3（第二阶段）：用于临床应用的3D全载玻片数字化和远程查看：Ramona将改进 MCAM-3D的处理速度使杜克大学医学院能够实时远程查看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存档方面的表现 样本材料，因为它对最终产品的销售6个月后，这个项目的结论。

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.