Our new paper ”Multi-modal imaging of a single mouse brain over five orders of magnitude of resolution” has been published in NeuroImage.
In this work, we demonstrate an imaging pipeline for a whole mouse brain using
- Whole-brain synchrotron x-ray microCT
- Serial electron microscopy (EM)
With EM, we get nano-scale reconstructions of individual synapses, giving us information we can bridge to the MRI scale using microCT as a sort of intermediate scaffolding. This pipeline will allow unprecedented insight into the microstructural drivers of the MRI signal, as well as help place EM volumetric reconstructions in their anatomical context.
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.
My primary contribution to this work was to demonstrate 3D alignment between the three modalities:
(a) and (b) show a region of the cerebellum in the low-resolution MRI data
(c) shows the region from (b) located within the microCT data
(d) shows the green inset from (c) with highlighted microvasculature and cell bodies
(e) shows the region from (d) located within the EM data with the same annotations
(f) shows the cyan inset from (e) with a highlighted synapse between two cells