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

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 cytologistandapos;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-3Dandapos;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.Currently, there is no way to efficiently digitize entire cytopathology specimens in 3D, which limits the accuracy and efficiency of cancer diagnosis in the hospital. In this project, Ramona Optics and the Duke University Medical Center propose to develop and test a new micro-camera array microscope (MCAM) that can efficiently image full cytopathology slides in 3D, which will improve patient care and speed-up workflows in the pathology lab. Our new MCAM-3D will be able to capture 1 µm3 resolution 3D images over a 12 cm2 x 50 µm thick volume for cytopathologists to view and focus through at alternative times and locations to aid with a variety of diagnostic tasks.