title: Creating High-Resolution Multiscale Maps of Human Tissue Using Multi-beam SEM.
abstract: Multi-beam scanning electron microscopy (mSEM) enables high-throughput, nano-resolution imaging of macroscopic tissue samples, providing an unprecedented means for structure-function characterization of biological tissues and their cellular inhabitants, seamlessly across multiple length scales. Here we describe computational methods to reconstruct and navigate a multitude of high-resolution mSEM images of the human hip. We calculated cross-correlation shift vectors between overlapping images and used a mass-spring-damper model for optimal global registration. We utilized the Google Maps API to create an interactive map and provide open access to our reconstructed mSEM datasets to both the public and scientific communities via our website www.mechbio.org. The nano- to macro-scale map reveals the tissue's biological and material constituents. Living inhabitants of the hip bone (e.g. osteocytes) are visible in their local extracellular matrix milieu (comprising collagen and mineral) and embedded in bone's structural tissue architecture, i.e. the osteonal structures in which layers of mineralized tissue are organized in lamellae around a central blood vessel. Multi-beam SEM and our presented methodology enable an unprecedented, comprehensive understanding of health and disease from the molecular to organ length scale.
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.
authors.forename: André F
authors.identifier: http://orcid.org/0000-0001-7066-1769
authors.initials: AF
authors.lastname: Pereira
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hageman
authors.affiliation: Carl Zeiss Microscopy GmbH, Oberkochen, Germany.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Garbowski
authors.affiliation: Carl Zeiss Microscopy GmbH, Oberkochen, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Riedesel
authors.affiliation: Orthopaedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.|TissuTex Pty. Ltd., Wentworth Falls, New South Wales, Australia.
authors.forename: Ulf
authors.initials: U
authors.lastname: Knothe
authors.affiliation: Carl Zeiss Microscopy GmbH, Oberkochen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Zeidler
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Knothe Tate
mesh_terms: D003196:Computer Graphics; D005272:Femur Neck / Q000648:ultrastructure*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008855:Microscopy, Electron, Scanning / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software; D014584:User-Computer Interface