ESRFEBS SCIENCE THAT SERVES I 11
Unlocking the complexity of the brain – an intricate
organ with over 80 billion neurons – is one of
humanity’s greatest scientific quests, with the
potential to transform how we understand and
treat neurodegenerative diseases. Yet mapping the
brain’s vast neuronal network – the ‘connectome’
– at subcellular resolution remains an immense
technical challenge. An innovative, ESRF-EBS-
enabled technique, X-ray nano-holotomography
(XNH), brings us closer than ever to seeing the
brain’s hidden architecture.
Developed at nanoprobe beamline ID16A, XNH
exploits ESRF-EBS’s highly coherent, intense X-ray
beams to achieve ~30 nm isotropic resolution across
large tissue volumes, imaging neuronal circuits
hundreds of times faster than traditional methods.
XNH is already changing the game: insect neural
circuits controlling movement have been elucidated
in the ERC-funded BRILLIANCE project; mouse
olfactory bulb circuits have been linked to function
across millimetre-scale tissue; and XNH imaging
of a pygmy squid has generated the first high-
resolution dataset of a whole cephalopod body
XNH has also produced the first multiple whole
brain datasets in zebrafish enabling discovery
of structural alterations in the context of Autism
Spectrum Disorder These advancements have
attracted international investment including from
the Francis Crick Institute and Harvard Medical
School A dedicated nanobioimaging facility at
beamline ID18 will scale up connectomics research
to larger more complex organisms and ultimately
towards a full mammalian brain connectome
TRANSFORMING
CONNECTOMICS RESEARCH
EBS SCIENCE
Connectomic reconstruction of a female
Drosophila ventral nerve cord A Azevedo
et al Nature 631 360368 2024
Mapping the nervous system of the Idiosepius
hallami pygmy squid insights from whole
animal Xray nanotomography imaging A
Correia et al bioRxiv 2025
StructureFunction Mapping of Olfactory Bulb
Circuits with Synchrotron Xray Nanotomography
Y Zhang et al bioRxiv 2025
False-coloured 3D rendering of X-ray nano-holotomography
scans at ESRF beamline ID16A of a small portion of pygmy
squid arms, showing suckers and the underlying neural
tracts. Image courtesy of ref. 3.
100 μm