Creating High-Resolution Multiscale Maps of Human Tissue Using Multi-beam SEM

PLoS Comput Biol. 2016 Nov 21;12(11):e1005217. doi: 10.1371/journal.pcbi.1005217. eCollection 2016 Nov.

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.

MeSH terms

  • Computer Graphics*
  • Femur Neck / ultrastructure*
  • Humans
  • Image Enhancement / methods*
  • Image Interpretation, Computer-Assisted / methods*
  • Microscopy, Electron, Scanning / methods*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Software
  • User-Computer Interface*

Grants and funding

Funding to these studies were supported through the Alexander von Humboldt Foundation and the Paul Trainor Foundation and awarded to Melissa Knothe Tate. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.