Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections.

Mlodzianoski, Michael J; Cheng-Hathaway, Paul J; Bemiller, Shane M; McCray, Tyler J; Liu, Sheng; Miller, David A; Lamb, Bruce T; Landreth, Gary E et al. · Nat Methods · 2018

basic_science · Level V

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Abstract

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.

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