Self-Supervised Missing Wedge Correction in Soft X-Ray Tomography: Towards Accurate Cellular Morphology and Volume Quantification

Chueh, S.; Lopez-Perez, M.; de Ceuninck van Capelle, C.; Ishikawa, T.; Zannotti, A.; Castro, V.; Calvo, G.; Gastaminza, P.; Mcintyre, C.; Rogers, D.; Oconnor, S.; Donnellan, M.; Simpson, J. C.; Kapishnikov, S.

doi:10.64898/2025.12.23.696166

bioRxiv · 10.64898/2025.12.23.696166

Self-Supervised Missing Wedge Correction in Soft X-Ray Tomography: Towards Accurate Cellular Morphology and Volume Quantification

Chueh, S.·Lopez-Perez, M.·de Ceuninck van Capelle, C.·Ishikawa, T.·Zannotti, A.·Castro, V.·Calvo, G.·Gastaminza, P.·Mcintyre, C.·Rogers, D.·Oconnor, S.·Donnellan, M.·Simpson, J. C.·Kapishnikov, S.

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Abstract

Soft X-Ray tomography (SXT) is a non-invasive bio-imaging technique that enables 3D imaging of cellular structures in large volume, with a unique resolution range that bridges the gap between fluorescence and transmission electron microscopy. However, a fundamental limitation, the missing wedge artefact caused by incomplete tilt-series acquisition, introduces systematic structural elongation in the reconstructed tomograms. This artifact compromises accurate quantitative biological analysis by overestimating cellular and organelle volumes. To overcome this persistent issue, we introduce a novel, self-supervised missing wedge correction model that learns key sine-wave patterns from existing SXT sinograms of the tilt series stacks. This model can be applied to recover the missing-angle region of the sinogram, reducing distortions and elongations in the reconstructed tomograms. We demonstrate a significant quantitative improvement in artifact removal, achieving faithful recovery of the spherical morphology of lipid droplets. We further applied this method to Plasmodium falciparum hemozoin crystals, a biomarker in antimalarial drug efficacy studies. Our model successfully reduced volume overestimation, achieving up to a 16% decrease in distorted volume. This level of precision is paramount for correctly interpreting the mode of action of antimalarial drugs.

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Chueh, S., Lopez-Perez, M., de Ceuninck van Capelle, C., Ishikawa, T., Zannotti, A., Castro, V., Calvo, G., Gastaminza, P., Mcintyre, C., Rogers, D., Oconnor, S., Donnellan, M., Simpson, J. C., Kapishnikov, S.. 2025-12-25. Self-Supervised Missing Wedge Correction in Soft X-Ray Tomography: Towards Accurate Cellular Morphology and Volume Quantification. https://doi.org/10.64898/2025.12.23.696166

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