Active PSF Shaping and Adaptive Optics Enable Volumetric Localization Microscopy through Brain Sections

Application of single-molecule switching nanoscopy (SMSN) beyond the coverslip surface poses substantial challenges due to sample-induced aberrations that distort and blur single-molecule emission patterns. We combined active shaping of point spread functions and efficient adaptive optics to enable robust 3D-SMSN imaging within tissues. This development allowed us to image through 30-μm-thick brain sections to visualize and reconstruct the morphology and the nanoscale details of amyloid-β filaments in a mouse model of Alzheimer’s disease.Active PSF shaping and adaptive optics are combined to enable 3D localization microscopy throughout thick tissues. The method was used to study the nanoscale architecture of amyloid fibrils in a mouse model of Alzheimer’s disease.

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