Population-scale Three-dimensional Reconstruction and Quantitative Profiling of Microglia Arbors

Megjhani, M., Rey-Villamizar, N., Merouane, A., Lu, Y., Mukherjee, A., Trett, K., Chong, P., Harris, C., Shain, W., Roysam, B. (July 2015) Population-scale Three-dimensional Reconstruction and Quantitative Profiling of Microglia Arbors. Bioinformatics, 31 (13). pp. 2190-2198. ISSN 1367-4803

URL: http://www.ncbi.nlm.nih.gov/pubmed/25701570
DOI: 10.1093/bioinformatics/btv109


MOTIVATION: The arbor morphologies of brain microglia are important indicators of cell activation. This paper fills the need for accurate, robust, adaptive, and scalable methods for reconstructing 3-D microglial arbors & quantitatively mapping microglia activation states over extended brain tissue regions. RESULTS: Thick rat brain sections (100-300mum) were multiplex immunolabeled for IBA1 and Hoechst, and imaged by step-and-repeat confocal microscopy with automated 3-D image mosaicing, producing seamless images of extended brain regions (e.g., 5,903x9,874x229 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. Availability: Experimental protocols, sample datasets, scalable open-source multi-threaded software implementation (C++, MATLAB) in the electronic supplement, and website (www.farsight-toolkit.org). CORRESPONDENCE: B. Roysam (broysam@central.uh.edu).

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > organs types and functions > brain
Investigative techniques and equipment > Whole Brain Circuit Mapping
CSHL Authors:
Communities: CSHL labs > Mitra lab
Depositing User: Matt Covey
Date: 1 July 2015
Date Deposited: 27 Feb 2015 16:45
Last Modified: 15 Jul 2021 20:15
PMCID: PMC4481841
Related URLs:
URI: https://repository.cshl.edu/id/eprint/31249

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