Efficient, gigapixel-scale, aberration-free whole slide scanner using angular ptychographic imaging with closed-form solution

Whole slide imaging provides a wide field-of-view (FOV) across cross-sections of biopsy or surgery samples, significantly facilitating pathological analysis and clinical diagnosis. Such high-quality images that enable detailed visualization of cellular and tissue structures are essential for effective patient care and treatment planning. To obtain such high-quality images for pathology applications, there is a need for scanners with high spatial bandwidth products, free from aberrations, and without the requirement for z-scanning. Here we report a whole slide imaging system based on angular ptychographic imaging with a closed-form solution (WSI-APIC), which offers efficient, tens-of-gigapixels, large-FOV, aberration-free imaging. WSI-APIC utilizes oblique incoherent illumination for initial high-level segmentation, thereby bypassing unnecessary scanning of the background regions and enhancing image acquisition efficiency. A GPU-accelerated APIC algorithm analytically reconstructs phase images with effective digital aberration corrections and improved optical resolutions. Moreover, an auto-stitching technique based on scale-invariant feature transform ensures the seamless concatenation of whole slide phase images. In our experiment, WSI-APIC achieved an optical resolution of 772 nm using a 10x/0.25 NA objective lens and captures 80-gigapixel aberration-free phase images for a standard 76.2 mm x 25.4 mm microscopic slide.

High-resolution, large field-of-view label-free imaging via aberration-corrected, closed-form complex field reconstruction

Computational imaging methods empower modern microscopy with the ability of producing high-resolution, large field-of-view, aberration-free images. One of the dominant computational label-free imaging methods, Fourier ptychographic microscopy (FPM), effectively increases the spatial-bandwidth product of conventional microscopy by using multiple tilted illuminations to achieve high-throughput imaging. However, its iterative reconstruction method is prone to parameter selection, can be computationally expensive and tends to fail under excessive aberrations. Recently, spatial Kramers-Kronig methods show it is possible to analytically reconstruct complex field but lacks the ability of correcting aberrations or providing extended resolution enhancement. Here, we present a closed-form method, termed APIC, which weds the strengths of both methods. A new analytical phase retrieval framework is established in APIC, which demonstrates, for the first time, the feasibility of analytically reconstructing the complex field associated with darkfield measurements. In addition, APIC can analytically retrieve complex aberrations of an imaging system with no additional hardware. By avoiding iterative algorithms, APIC requires no human designed convergence metric and always obtains a closed-form complex field solution. The faithfulness and correctness of APIC's reconstruction are guaranteed due to its analytical nature. We experimentally demonstrate that APIC gives correct reconstruction result while FPM fails to do so when constrained to the same number of measurements. Meanwhile, APIC achieves 2.8 times faster computation using image tile size of 256 (length-wise). We also demonstrate APIC is unprecedentedly robust against aberrations compared to FPM - APIC is capable of addressing aberration whose maximal phase difference exceeds 3.8${\pi}$ when using a NA 0.25 objective in experiment.