title: ScaleS: an optical clearing palette for biological imaging.
abstract: Optical clearing methods facilitate deep biological imaging by mitigating light scattering in situ. Multi-scale high-resolution imaging requires preservation of tissue integrity for accurate signal reconstruction. However, existing clearing reagents contain chemical components that could compromise tissue structure, preventing reproducible anatomical and fluorescence signal stability. We developed ScaleS, a sorbitol-based optical clearing method that provides stable tissue preservation for immunochemical labeling and three-dimensional (3D) signal rendering. ScaleS permitted optical reconstructions of aged and diseased brain in Alzheimer's disease models, including mapping of 3D networks of amyloid plaques, neurons and microglia, and multi-scale tracking of single plaques by successive fluorescence and electron microscopy. Human clinical samples from Alzheimer's disease patients analyzed via reversible optical re-sectioning illuminated plaque pathogenesis in the z axis. Comparative benchmarking of contemporary clearing agents showed superior signal and structure preservation by ScaleS. These findings suggest that ScaleS is a simple and reproducible method for accurate visualization of biological tissue.
authors.affiliation: Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hama
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hioki
authors.affiliation: Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Namiki
authors.affiliation: Biotechnological Optics Research Team, Center for Advanced Photonics, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Hoshida
authors.affiliation: Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurokawa
authors.affiliation: Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Ishidate
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Support Unit for Animal Resources Development, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Akagi
authors.affiliation: Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Saido
authors.affiliation: Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Wako-city, Saitama, Japan.|Biotechnological Optics Research Team, Center for Advanced Photonics, RIKEN, Wako-city, Saitama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D058225:Plaque, Amyloid / Q000473:pathology; D016707:Tissue Fixation / Q000379:methods*