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PreprintCC BYbioRxiv

Diffusion MR Microscopy of the Human Hippocampus at 50 μm Resolution at 14.1 T for 3D Virtual Histology

  1. 1Zhejiang University

Abstract

Bridging the gap between macroscopic neuroimaging and microscopic histology remains a challenge in neuroscience. Here, we present a technical feasibility study of diffusion MR microscopy (dMRM) in the ex vivo human hippocampus using a 14.1 T ultrahigh-field MRI system. Mid-hippocampal blocks from control and Alzheimers disease (AD) patients were acquired at 50 x 50 x 100 {micro}m3, representing, to our knowledge, the highest resolution reported for human brain diffusion MRI. At a spatial scale approaching cellular dimensions, dMRM maps and tractography showed close correspondence with immunohistological markers of axons and dendrites. The acquired data delineated six hippocampal laminae, distinguished the inner and outer molecular layers, and preserved short, lamina-specific trajectories that became attenuated or blurred at 100 {micro}m resolution. Tractography further depicted the major components of the hippocampal tri-synaptic circuit--the perforant path, mossy fibers, and Schaffer collaterals in 3D. In the AD specimen, dMRM revealed reduced laminar contrast, local discontinuities, and altered radial and tangential fibers that were paralleled by pathological staining. With the 3D nondestructive characterization of human brain microstructure and circuitry, ex vivo dMRM showed its potential toward the goal of 3D virtual histology.

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BibTeX
@misc{shen2026diffusion,
  title = {{Diffusion MR Microscopy of the Human Hippocampus at 50 μm Resolution at 14.1 T for 3D Virtual Histology}},
  author = {Y. Shen and Z. Yu and Q. Zhu and Z. Zhao and P. Wang and Y. Yin and P. Jiang and C. Wang and X. Kong and J. Zhang and D. Wu},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.04.749425},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749425v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Diffusion MR Microscopy of the Human Hippocampus at 50 μm Resolution at 14.1 T for 3D Virtual Histology
AU  - Y. Shen
AU  - Z. Yu
AU  - Q. Zhu
AU  - Z. Zhao
AU  - P. Wang
AU  - Y. Yin
AU  - P. Jiang
AU  - C. Wang
AU  - X. Kong
AU  - J. Zhang
AU  - D. Wu
PY  - 2026
DA  - 2026/09/04
PB  - bioRxiv
DO  - 10.64898/2026.09.04.749425
UR  - https://www.biorxiv.org/content/10.64898/2026.09.04.749425v1
AB  - Bridging the gap between macroscopic neuroimaging and microscopic histology remains a challenge in neuroscience. Here, we present a technical feasibility study of diffusion MR microscopy (dMRM) in the ex vivo human hippocampus using a 14.1 T ultrahigh-field MRI system. Mid-hippocampal blocks from control and Alzheimers disease (AD) patients were acquired at 50 x 50 x 100 {micro}m3, representing, to our knowledge, the highest resolution reported for human brain diffusion MRI. At a spatial scale approaching cellular dimensions, dMRM maps and tractography showed close correspondence with immunohistological markers of axons and dendrites. The acquired data delineated six hippocampal laminae, distinguished the inner and outer molecular layers, and preserved short, lamina-specific trajectories that became attenuated or blurred at 100 {micro}m resolution. Tractography further depicted the major components of the hippocampal tri-synaptic circuit--the perforant path, mossy fibers, and Schaffer collaterals in 3D. In the AD specimen, dMRM revealed reduced laminar contrast, local discontinuities, and altered radial and tangential fibers that were paralleled by pathological staining. With the 3D nondestructive characterization of human brain microstructure and circuitry, ex vivo dMRM showed its potential toward the goal of 3D virtual histology.
ER  -