Mechanical de-skewing enables high-resolution imaging of thin tissue slices with a mesoSPIM light-sheet microscope

Optical clearing combined with light-sheet microscopy enables high-resolution imaging of extended tissue at scale. However, standard mesoSPIM systems are optimised for intact organs and are not suited to thin tissue slices. We present an oblique compensation scanning method using obliquely mounted samples held between refractive-index-matched slides in a 3D-printed frame. This enables mechanical de-skewing during acquisition, minimising post-processing requirements. We demonstrate feasibility in fluorescent bead phantoms and rabbit heart tissue, achieving a 4.8 × reduction in processing time and a 1.5 × improvement in axial resolution ((13.15±1.36) μm to (8.72±1.80) μm) compared to conventional <i>z</i> scan. The oblique compensation acquisition method extends mesoSPIM's utility to fragile, laterally extended tissue sections.

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Publication Details

Journal
Biomedical Optics Express
Published
2025-12-23
DOI
https://doi.org/10.1364/boe.583082
Primary Topic
Advanced Fluorescence Microscopy Techniques
Type
article
Field-Weighted Citation Impact
0.00

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article

Mechanical de-skewing enables high-resolution imaging of thin tissue slices with a mesoSPIM light-sheet microscope

L. A. Williamson, Eline Huethorst, Camilla Olianti, Leonardo Sacconi et al.
Biomedical Optics Express
Advanced Fluorescence Microscopy Techniques
article

Mechanical de-skewing enables high-resolution imaging of thin tissue slices with a mesoSPIM light-sheet microscope

L. A. Williamson, Eline Huethorst, Camilla Olianti, Leonardo Sacconi, Erin Boland, Godfrey L. Smith, Sharika Mohanan, Steven Milan Moreno, Marie-Caroline Muellenbroich, Ahmed Elnageh
article en

Abstract

Optical clearing combined with light-sheet microscopy enables high-resolution imaging of extended tissue at scale. However, standard mesoSPIM systems are optimised for intact organs and are not suited to thin tissue slices. We present an oblique compensation scanning method using obliquely mounted samples held between refractive-index-matched slides in a 3D-printed frame. This enables mechanical de-skewing during acquisition, minimising post-processing requirements. We demonstrate feasibility in fluorescent bead phantoms and rabbit heart tissue, achieving a 4.8 × reduction in processing time and a 1.5 × improvement in axial resolution ((13.15±1.36) μm to (8.72±1.80) μm) compared to conventional <i>z</i> scan. The oblique compensation acquisition method extends mesoSPIM's utility to fragile, laterally extended tissue sections.

Biomedical Optics ExpressVol. 17(2)
Qinetiq (United Kingdom) (GB), Istituto di Fisiologia Clinica (IT), Alleghany County Schools (US), European Theoretical Spectroscopy Facility (BE), Czech Academy of Sciences, Institute of Physiology (CZ), University of Glasgow (GB)
British Heart Foundation, Medical Research Scotland, Engineering and Physical Sciences Research Council
Openalex Percentile: Top 21%
Advanced Fluorescence Microscopy Techniques
DOIOpen Access PDFOpenAlex
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Mechanical de-skewing enables high-resolution imaging of thin tissue slices with a mesoSPIM light-sheet microscope — L. A. Williamson, Eline Huethorst, et al. · Biomedical Optics Express (2025) | TGRS Research Map | TGRS