title: Automated quantification of three-dimensional organization of fiber-like structures in biological tissues.
abstract: Fiber-like structures are prevalent in biological tissues, yet quantitative approaches to assess their three-dimensional (3D) organization are lacking. We develop 3D directional variance, as a quantitative biomarker of truly 3D fibrillar organization by extending the directional statistics formalism developed for describing circular data distributions (i.e. when 0° and 360° are equivalent) to axial ones (i.e. when 0° and 180° are equivalent). Significant advantages of this analysis include its time efficiency, sensitivity and ability to provide quantitative readouts of organization over different size scales of a given data set. We establish a broad range of applications for this method by characterizing collagen fibers, neuronal axons and fibroblasts in the context of cancer diagnostics, traumatic brain injury and cell-matrix interactions in developing engineered tissues. This method opens possibilities for unraveling in a sensitive, and quantitative manner the organization of essential fiber-like structures in tissues and ultimately its impact on tissue function.
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Pouli
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
authors.forename: Disha
authors.initials: D
authors.lastname: Sood
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
authors.forename: Aswin
authors.initials: A
authors.lastname: Sundarakrishnan
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, 02111, USA.
authors.forename: Carrie K
authors.initials: CK
authors.lastname: Hui Mingalone
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, 02111, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Arendt
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Alonzo
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA; Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, 72701, USA.
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Quinn
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, 02111, USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kuperwasser
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, 02111, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Lahey Hospital & Medical Center, Burlington, MA, 01805, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schnelldorfer
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA. Electronic address: Irene.Georgakoudi@tufts.edu.
authors.forename: Irene
authors.initials: I
authors.lastname: Georgakoudi
mesh_terms: D000465:Algorithms; D001369:Axons / Q000648:ultrastructure*; D004547:Elastic Tissue / Q000648:ultrastructure*; D024022:Fibrillar Collagens / Q000648:ultrastructure*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D000069550:Machine Learning; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D024022:Fibrillar Collagens
keywords: Cancer; Collagen fiber; Multi-photon microscopy; Neuronal axon; Three-dimensional organization; Traumatic brain injury