Isotropic, aberration-corrected light sheet microscopy for rapid high-resolution imaging of cleared tissue Article Swipe
Mostafa Aakhte
,
Geoffrey A. Mueller
,
Joe Li
,
Kurt R. Weiss
,
Lennart Roos
,
Aleyna M. Diniz
,
Jan Wenzel
,
Markus Schwaninger
,
Tobias Moser
,
Jan Huisken
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.02.21.639411
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.02.21.639411
Light sheet microscopy is the ideal technique for multiscale imaging of large and cleared tissues, and it is desirable to achieve the highest possible isotropic resolution across the entire sample. However, isotropic resolution for a centimeter-sized sample has only been achieved with slow and often aberrated, axially scanned light sheets, resulting in a low resolution of several micrometers. Here, we introduce a compact, high-speed light sheet fluorescence microscope with isotropic sub-micron resolution optimized for cleared tissue. We introduce three major opto-mechanical innovations using off-the-shelf optics to achieve an isotropic resolution of 850 nm across samples up to 1 cm 3 and refractive indices ranging from 1.33 to 1.56, using mechanical tiling with a field of view of 800 µm × 800 µm. We show that combining an air objective and a meniscus lens achieves an axially swept light sheet with sub-micron diffraction-limited resolution and aberration correction. The effective field of view is increased 2-fold by correcting the field curvature of the light sheet with a concave mirror in the remote focusing unit. Furthermore, the imaging speed is enhanced 10-fold by adapting the light sheet’s motion with a closed-loop feedback, reaching 100 frames per second while maintaining isotropic resolution across the large field of view. Finally, we showcase the performance of our light sheet system for imaging from subcellular up to centimeter scale in cleared zebrafish, mouse cochlea, and mouse brain using various clearing methods.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.02.21.639411
- OA Status
- gold
- Cited By
- 1
- References
- 40
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4407838829
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4407838829Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.02.21.639411Digital Object Identifier
- Title
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Isotropic, aberration-corrected light sheet microscopy for rapid high-resolution imaging of cleared tissueWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-02-21Full publication date if available
- Authors
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Mostafa Aakhte, Geoffrey A. Mueller, Joe Li, Kurt R. Weiss, Lennart Roos, Aleyna M. Diniz, Jan Wenzel, Markus Schwaninger, Tobias Moser, Jan HuiskenList of authors in order
- Landing page
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https://doi.org/10.1101/2025.02.21.639411Publisher landing page
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://resolver.sub.uni-goettingen.de/purl?gro-2/151211Direct OA link when available
- Concepts
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Clearance, Light sheet fluorescence microscopy, Microscopy, Isotropy, Resolution (logic), Optics, High resolution, Materials science, Biophysics, Biomedical engineering, Physics, Scanning confocal electron microscopy, Medicine, Biology, Computer science, Geology, Artificial intelligence, Remote sensing, UrologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
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40Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2030224529, https://openalex.org/W2031312855, https://openalex.org/W2094643072, https://openalex.org/W2023701980, https://openalex.org/W1969649188, https://openalex.org/W2087451538, https://openalex.org/W2010114799, https://openalex.org/W2424791915, https://openalex.org/W2900192141, https://openalex.org/W3158298584, https://openalex.org/W2598427385, https://openalex.org/W1487216741, https://openalex.org/W2982421002, https://openalex.org/W2973461991, https://openalex.org/W4393233092, https://openalex.org/W2905344744, https://openalex.org/W2010956007, https://openalex.org/W2068391384, https://openalex.org/W4304123577, https://openalex.org/W4402006415, https://openalex.org/W4399578563, https://openalex.org/W2972005632, https://openalex.org/W4280562732, https://openalex.org/W4399319681, https://openalex.org/W2944964735, https://openalex.org/W4396517572, https://openalex.org/W2891127204, https://openalex.org/W2887693294, https://openalex.org/W2886288118, https://openalex.org/W2763985063, https://openalex.org/W2394641095, https://openalex.org/W2110021835, https://openalex.org/W4406810813, https://openalex.org/W3161255713, https://openalex.org/W2755888480, https://openalex.org/W2999406023, https://openalex.org/W2167279371, https://openalex.org/W2966422204, https://openalex.org/W2408110716, https://openalex.org/W3006529112 |
| referenced_works_count | 40 |
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| abstract_inverted_index.3 | 100 |
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