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Fourier-based three-dimensional multistage transformer for aberration correction in multicellular specimens.
Thayer Alshaabi1,2, Daniel E Milkie3, Gaoxiang Liu4
1Howard Hughes Medical Institute, Ashburn, VA, USA. alshaabit@hhmi.org.
Nature Methods
|October 1, 2025
Summary
We developed AOVIFT, a machine learning framework that corrects optical aberrations in microscopy. This AI-powered solution enhances image resolution and contrast without complex hardware, making high-resolution imaging more accessible.
Area of Science:
- Microscopy and Imaging Science
- Artificial Intelligence in Biology
- Optical Physics
Background:
- High-resolution tissue imaging is limited by optical aberrations, reducing image quality.
- Conventional adaptive optics (AO) solutions are complex, costly, and slow for large-scale imaging.
Purpose of the Study:
- To introduce AOVIFT, a novel machine learning framework for aberration sensing and correction in microscopy.
- To reduce the computational cost and hardware requirements for high-resolution imaging.
Main Methods:
- Developed AOVIFT, a machine learning framework using a 3D multistage vision transformer operating on Fourier domain embeddings.
- Inferred optical aberrations and restored diffraction-limited performance in puncta-labeled specimens.
- Validated on live gene-edited zebrafish embryos, correcting aberrations with a deformable mirror or post-acquisition deconvolution.
Main Results:
- AOVIFT achieved aberration correction with reduced computational cost, training time, and memory footprint compared to existing methods.
- Successfully demonstrated correction of spatially varying aberrations in live biological samples.
- Enabled high-resolution volumetric microscopy with a simplified experimental workflow.
Conclusions:
- AOVIFT effectively corrects optical aberrations, enhancing resolution and contrast in microscopy.
- The AI-driven approach eliminates the need for wavefront sensing hardware, lowering technical barriers.
- AOVIFT facilitates broader access to high-resolution volumetric imaging across various biological applications.

