title: High-throughput 3D whole-brain quantitative histopathology in rodents.
abstract: Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer's disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques.
authors.affiliation: Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
authors.forename: Michel E
authors.initials: ME
authors.lastname: Vandenberghe
authors.affiliation: Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Hérard
authors.affiliation: Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Souedet
authors.affiliation: Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
authors.forename: Elmahdi
authors.initials: E
authors.lastname: Sadouni
authors.affiliation: Brain and Spine Institute (ICM), 75013 Paris, France.
authors.forename: Mathieu D
authors.initials: MD
authors.lastname: Santin
authors.affiliation: Sanofi, Therapeutic Strategy Unit Aging, 91380 Chilly-Mazarin, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Briet
authors.affiliation: IPSEN Innovation, 91140 Les Ulis, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Carré
authors.affiliation: IPSEN Innovation, 91140 Les Ulis, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Schulz
authors.affiliation: Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.affiliation: IPSEN Innovation, 91140 Les Ulis, France.
authors.forename: Pierre-Etienne
authors.initials: PE
authors.lastname: Chabrier
authors.affiliation: Sanofi, Therapeutic Strategy Unit Aging, 91380 Chilly-Mazarin, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rooney
authors.affiliation: Sanofi, Therapeutic Strategy Unit Aging, 91380 Chilly-Mazarin, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Debeir
authors.affiliation: Sanofi, Therapeutic Strategy Unit Aging, 91380 Chilly-Mazarin, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanchard
authors.affiliation: Sanofi, Therapeutic Strategy Unit Aging, 91380 Chilly-Mazarin, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
authors.affiliation: Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Dhenain
authors.affiliation: Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Delzescaux
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology / Q000648:ultrastructure; D001931:Brain Mapping; D004195:Disease Models, Animal; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D051379:Mice; D012984:Software