Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections.
Michael J MlodzianoskiPaul J Cheng-HathawayShane M BemillerTyler J McCraySheng LiuDavid A MillerBruce T LambGary E LandrethFang HuangPublished in: Nature methods (2018)
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.
Keyphrases
- single molecule
- atomic force microscopy
- mouse model
- resting state
- living cells
- white matter
- high resolution
- functional connectivity
- high glucose
- gene expression
- diabetic rats
- cerebral ischemia
- oxidative stress
- multiple sclerosis
- drug induced
- machine learning
- endothelial cells
- blood brain barrier
- stress induced
- optical coherence tomography
- solid state
- brain injury