title: Population-scale three-dimensional reconstruction and quantitative profiling of microglia arbors.
abstract: BACKGROUND
  The arbor morphologies of brain microglia are important indicators of cell activation. This article fills the need for accurate, robust, adaptive and scalable methods for reconstructing 3-D microglial arbors and quantitatively mapping microglia activation states over extended brain tissue regions.
  
  
  RESULTS
  Thick rat brain sections (100-300 µm) were multiplex immunolabeled for IBA1 and Hoechst, and imaged by step-and-image confocal microscopy with automated 3-D image mosaicing, producing seamless images of extended brain regions (e.g. 5903 × 9874 × 229 voxels). An over-complete dictionary-based model was learned for the image-specific local structure of microglial processes. The microglial arbors were reconstructed seamlessly using an automated and scalable algorithm that exploits microglia-specific constraints. This method detected 80.1 and 92.8% more centered arbor points, and 53.5 and 55.5% fewer spurious points than existing vesselness and LoG-based methods, respectively, and the traces were 13.1 and 15.5% more accurate based on the DIADEM metric. The arbor morphologies were quantified using Scorcioni's L-measure. Coifman's harmonic co-clustering revealed four morphologically distinct classes that concord with known microglia activation patterns. This enabled us to map spatial distributions of microglial activation and cell abundances.
  
  
  METHODS
  Experimental protocols, sample datasets, scalable open-source multi-threaded software implementation (C++, MATLAB) in the electronic supplement, and website (www.farsight-toolkit.org). http://www.farsight-toolkit.org/wiki/Population-scale_Three-dimensional_Reconstruction_and_Quanti-tative_Profiling_of_Microglia_Arbors
  
  
  BACKGROUND
  broysam@central.uh.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Murad
authors.initials: M
authors.lastname: Megjhani
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rey-Villamizar
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Amine
authors.initials: A
authors.lastname: Merouane
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Trett
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Chong
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Harris
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: William
authors.initials: W
authors.lastname: Shain
authors.affiliation: Department of Electrical and Computer Engineering, University of Houston, Houston, TX, USA, Center for Integrative Brain Research, Seattle Children's Hospital, Seattle, WA 98101, USA and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Badrinath
authors.initials: B
authors.lastname: Roysam
mesh_terms: D000465:Algorithms; D000818:Animals; D001921:Brain / Q000166:cytology*; D001931:Brain Mapping / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D017628:Microglia / Q000166:cytology*; D010363:Pattern Recognition, Automated; D051381:Rats; D012984:Software