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Computational imaging modalities for multi-focal whole-slide imaging systems

Leon van der Graaff, Geert J. L. H. van Leenders, Fanny Boyaval, and Sjoerd Stallinga

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Abstract

Whole-slide imaging systems can generate full-color image data of tissue slides efficiently, which are needed for digital pathology applications. This paper focuses on a scanner architecture that is based on a multi-line image sensor that is tilted with respect to the optical axis, such that every line of the sensor scans the tissue slide at a different focus level. This scanner platform is designed for imaging with continuous autofocus and inherent color registration at a throughput of the order of 400 MPx/s. Here, single-scan multi-focal whole-slide imaging, enabled by this platform, is explored. In particular, two computational imaging modalities based on multi-focal image data are studied. First, 3D imaging of thick absorption stained slides (${\sim}60\,\,\unicode{x00B5}{\rm m}$) is demonstrated in combination with deconvolution to ameliorate the inherently weak contrast in thick-tissue imaging. Second, quantitative phase tomography is demonstrated on unstained tissue slides and on fluorescently stained slides, revealing morphological features complementary to features made visible with conventional absorption or fluorescence stains. For both computational approaches simplified algorithms are proposed, targeted for straightforward parallel processing implementation at ${\sim}{\rm{GPx/s}}$ throughputs.

© 2020 Optical Society of America

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Supplementary Material (11)

NameDescription
Visualization 1       Side-by-side view of raw and deconvolved multi-layer scan of a 60 µm thick, HE stained normal human rectal mucosa section.
Visualization 2       Side-by-side view of raw and deconvolved multi-layer scan of a 60 µm thick, cleared, and HE stained human prostate section.
Visualization 3       Total estimated optical thickness for a multi-layer phase contrast image of a 5 µm thick human prostate TMA section prepared for ERBB2 detection using FISH across length scales.
Visualization 4       Color-code maximum intensity projection of a multi-layer phase contrast image of a 5 µm thick human prostate TMA section prepared for ERBB2 detection using FISH across length scales.
Visualization 5       Reference fluorescence image of a 5 µm thick human prostate TMA section prepared for ERBB2 detection using FISH, for comparison to computational phase contrast imaging.
Visualization 6       Total estimated optical thickness for a multi-layer phase contrast image of a 4 µm thick human rectum section across length scales.
Visualization 7       Color-code maximum intensity projection of a multi-layer phase contrast image of a 4 µm thick human rectum section across length scales.
Visualization 8       Reference fluorescence image of a multi-layer phase contrast image of a 4 µm thick human rectum section across length scales.
Visualization 9       Total estimated optical thickness of a multi-layer phase contrast image of an unstained, 4 µm thick human prostate section across length scales.
Visualization 10       Color-coded maximum intensity projection of a multi-layer phase contrast image of an unstained, 4 µm thick human prostate section across length scales.
Visualization 11       Reference HE stained image of a section obtained from the same block as used for a multi-layer phase contrast image of an unstained, 4 µm thick human prostate section, across length scales.

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