Multi-modal imaging of a single mouse brain over five orders of magnitude of resolution

Neuroimage. 2021 Sep;238:118250. doi: 10.1016/j.neuroimage.2021.118250. Epub 2021 Jun 9.


Mammalian neurons operate at length scales spanning six orders of magnitude; they project millimeters to centimeters across brain regions, are composed of micrometer-scale-diameter myelinated axons, and ultimately form nanometer scale synapses. Capturing these anatomical features across that breadth of scale has required imaging samples with multiple independent imaging modalities. Translating between the different modalities, however, requires imaging the same brain with each. Here, we imaged the same postmortem mouse brain over five orders of spatial resolution using MRI, whole brain micrometer-scale synchrotron x-ray tomography (μCT), and large volume automated serial electron microscopy. Using this pipeline, we can track individual myelinated axons previously relegated to axon bundles in diffusion tensor MRI or arbitrarily trace neurons and their processes brain-wide and identify individual synapses on them. This pipeline provides both an unprecedented look across a single brain's multi-scaled organization as well as a vehicle for studying the brain's multi-scale pathologies.

Keywords: Connectomics; Echo planar spectroscopic imaging; Electron microscopy; MRI; Multi-scale imaging; Synchrotron source x-ray tomography; Whole mouse brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Connectome
  • Magnetic Resonance Imaging
  • Mice
  • Microscopy, Electron
  • Multimodal Imaging / methods*
  • Tomography, X-Ray Computed