# Advances in multiscale myelin imaging: from classical histology to functional insights

**Authors:** Kentaro Okuyama, Yuji Komaki, Motonari Ishihara, Yuma Kurosaki, Saki Tsuchiya, Manabu Hayatsu, Junpei Nakayama, Keiko Uchiyama, Kosuke Itoh, Toshihiro Nagai, Tomoko Shindo, Nobuko Moritoki, Hiroyuki Kawashima, Shinsuke Shibata

PMC · DOI: 10.3389/fncel.2026.1771168 · Frontiers in Cellular Neuroscience · 2026-02-18

## TL;DR

This paper reviews advances in imaging technologies that help understand myelin's role in the nervous system, from large-scale scans to detailed nano-scale observations.

## Contribution

The paper provides a comprehensive, multi-scale overview of imaging techniques for myelin biology and emphasizes the need for integrating these methods.

## Key findings

- Non-invasive imaging techniques like MRI and PET reveal in vivo myelin architecture and molecular changes.
- Advanced light microscopy enables visualization of cellular dynamics and molecular interactions at the micro-scale.
- Nano-scale electron microscopy techniques resolve ultrastructural details of myelin biology.

## Abstract

Scientific understanding of myelin, the lipid-rich sheath of axons essential for vertebrate rapid neuronal communication, has evolved considerably. Enabled by major advances in imaging technology, research has shifted from viewing myelin as a static insulator to investigating the dynamic roles of myelinating glia in nervous system development, function, and pathophysiology. This review aimed to provide a comprehensive, multi-scale overview of the imaging toolkit for myelin biology, from foundational histology to cutting-edge advances. At the macro- and meso-scales, non-invasive modalities like magnetic resonance imaging and positron emission tomography reveal in vivo myelin architecture and molecular changes, offering critical insights into large-scale pathology. At the micro-scale, advanced light microscopy now visualizes cellular dynamics and molecular interactions with remarkable clarity. Finally, at the nano-scale, sophisticated electron microscopy techniques—including volume electron microscopy and correlative approaches—resolve the ultrastructural basis of biological phenomena with unparalleled detail. As no single modality can capture the full biological context, a holistic understanding of glial biology requires the strategic integration of these multi-scale techniques with advanced computational analysis. This integrated approach is essential for revealing the full spectrum of myelin biology and uncovering novel targets for therapeutic intervention.

## Full-text entities

- **Genes:** Egr2 (early growth response 2) [NCBI Gene 13654] {aka Egr-2, Krox-20, Krox20, NGF1-B, Zfp-25, Zfp-6}, MBP (myelin basic protein) [NCBI Gene 4155], Olig2 (oligodendrocyte transcription factor 2) [NCBI Gene 50913] {aka Bhlhb1, Olg-2, Oligo2, RK17, bHLHe19}, Mpz (myelin protein zero) [NCBI Gene 17528] {aka Mpp, P-zero, P0}, MOG (myelin oligodendrocyte glycoprotein) [NCBI Gene 4340] {aka BTN6, BTNL11, MOGIG2, NRCLP7}, Cnp (2',3'-cyclic nucleotide 3' phosphodiesterase) [NCBI Gene 12799] {aka CNPase, Cnp-1, Cnp1}, MPZ (myelin protein zero) [NCBI Gene 4359] {aka CMT1, CMT1B, CMT2I, CMT2J, CMT4E, CMTDI3}, CLDN11 (claudin 11) [NCBI Gene 5010] {aka HLD22, OSP, OTM}, Mbp (myelin basic protein) [NCBI Gene 17196] {aka Hmbpr, golli-mbp, jve, mld, shi}, Ngfr (nerve growth factor receptor (TNFR superfamily, member 16)) [NCBI Gene 18053] {aka LNGFR, Tnfrsf16, p75, p75NGFR, p75NTR}, MAG (myelin associated glycoprotein) [NCBI Gene 4099] {aka GMA, S-MAG, SIGLEC-4A, SIGLEC4, SIGLEC4A, SPG75}, Wnt1 (wingless-type MMTV integration site family, member 1) [NCBI Gene 22408] {aka Int-1, Wnt-1, sw, swaying}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Cspg4 (chondroitin sulfate proteoglycan 4) [NCBI Gene 121021] {aka 4732461B14Rik, AN2, Cspg4a, NG2}, S100b (S100 protein, beta polypeptide, neural) [NCBI Gene 20203] {aka Bpb}, Pmp22 (peripheral myelin protein 22) [NCBI Gene 18858] {aka Gas-3, HNPP, PMP-22, TRE002, Tr, trembler}, Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, CNP (2',3'-cyclic nucleotide 3' phosphodiesterase) [NCBI Gene 1267] {aka CN37, CNP1, HLD20}, Sox10 (SRY (sex determining region Y)-box 10) [NCBI Gene 20665] {aka Dom, Sox21, gt}, Plp1 (proteolipid protein (myelin) 1) [NCBI Gene 18823] {aka DM20, Plp, jimpy, jp, msd, rsh}, Uchl1 (ubiquitin carboxy-terminal hydrolase L1) [NCBI Gene 22223] {aka PGP 9.5, PGP9.5, UCH-L1, UCHL-1, gad}, Galc (galactosylceramidase) [NCBI Gene 14420] {aka 2310068B06Rik, A930008M05Rik, Gacy, twi, twitcher}, Nkx2-2 (NK2 homeobox 2) [NCBI Gene 18088] {aka Nkx-2.2, Nkx2.2, tinman}, Pdgfra (platelet derived growth factor receptor, alpha polypeptide) [NCBI Gene 18595] {aka CD140a, Pdgfr-2}, PLP1 (proteolipid protein 1) [NCBI Gene 5354] {aka GPM6C, HLD1, MMPL, PLP, PLP/DM20, PMD}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Tyms (thymidylate synthase) [NCBI Gene 22171] {aka Ts}
- **Diseases:** peripheral neuropathies (MESH:D010523), amyloid (MESH:C000718787), axonal degeneration (MESH:D009410), Charcot-Marie-Tooth syndrome (MESH:D002607), multiple sclerosis (MESH:D009103), demyelinating diseases (MESH:D003711), LMs (MESH:D020795), EM (MESH:D028361), nerve injury (MESH:D000080902), neurodegenerative (MESH:D019636), amyotrophic lateral sclerosis (MESH:D000690), CNS diseases (MESH:D002493), swelling (MESH:D004487)
- **Chemicals:** lipid (MESH:D008055), Resin (MESH:D012116), thioflavin-T (MESH:C009462), 18F-florbetaben (MESH:C527756), KOH (MESH:C029943), iodine (MESH:D007455), water (MESH:D014867), Luxol Fast Blue (MESH:C018588), Hoechst 33258 (MESH:D006690), osmium (MESH:D009992), cacodylate (MESH:D002101), toluidine blue (MESH:D014048), formaldehyde (MESH:D005557), ethanol (MESH:D000431), ice (MESH:D007053), glutaraldehyde (MESH:D005976), biotin (MESH:D001710), eosin (MESH:D004801), 18F-flutemetamol (MESH:C581552), phosphate (MESH:D010710), Nile red (MESH:C044808), Osmium tetroxide (MESH:D009993), hematoxylin (MESH:D006416), Paraffin (MESH:D010232), Gallyas silver (-), silicon (MESH:D012825), gold (MESH:D006046), 18F-florbetapir (MESH:C545186), cuprizone (MESH:D003471), stilbene (MESH:D013267), Sudan Black B (MESH:C016118)
- **Species:** Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Sus scrofa (pig, species) [taxon 9823], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** p.Thr65Ala

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12956672/full.md

## References

203 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956672/full.md

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Source: https://tomesphere.com/paper/PMC12956672