Diffusion tensor imaging of whole human brains during long-term formaldehyde fixation: Temporal evolution of diffusion parameters, post-mortem conditions, and dependence on tissue structure
- 1Department of Neuroradiology, University of Luebeck
Abstract
Purpose: Post-mortem Diffusion Magnetic Resonance Imaging (dMRI) findings on fixation-related changes in diffusion tensor imaging (DTI) parameters remain inconsistent, partly due to lower diffusion weighting and sparse early-fixation sampling. This study investigated how post-mortem tissue condition, fixation progression, and diffusion weighting shape DTI parameters in whole human brains, including whether an ex-vivo-adjusted protocol also suits in-situ and early fixation measurements. Methods: Six neurologically healthy whole human brains (post-mortem interval (PMI) 12 - 24 h) were scanned across tissue conditions, including an in-vivo reference cohort. Five brains were scanned longitudinally through immersion fixation (0 - 150 days), yielding 175 datasets with dense early sampling. Diffusion measurements at b-values 1000 - 4000 s/mm2 assessed the influence of diffusion weighting on DTI parameters. Analyses covered multiple white- and gray-matter regions and within white matter stratification by fiber orientation dispersion ({kappa}). Results: The largest mean diffusivity (MD) shift occurred between in-vivo and in-situ, whereas fractional anisotropy (FA) changed most strongly during early fixation. During immersion fixation, MD showed reproducible monoexponential saturation, while FA was heterogeneous across brains. PMI, {kappa}, and regional anatomy explained substantial FA heterogeneity across specimens. Qualitatively, the fixationrelated changes matched across diffusion weightings, but precision across specimens was highest at b-value 4000 s/mm2. Conclusion: During fixation, MD is a robust temporal marker, whereas FA requires microstructureaware interpretation. Diffusion weighting modulates how clearly fixation effects can be resolved, but the same qualitative fixation dynamics remained detectable at in-vivo-like weighting with reduced precision.
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BibTeX
@misc{luethi2026diffusion,
title = {{Diffusion tensor imaging of whole human brains during long-term formaldehyde fixation: Temporal evolution of diffusion parameters, post-mortem conditions, and dependence on tissue structure}},
author = {N. Luethi and F. Fritz and B. Fricke and J. M. Oeschger and T. Streubel and H. Mushumba and K. Pueschel and S. Mohammadi},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748254},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748254v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Diffusion tensor imaging of whole human brains during long-term formaldehyde fixation: Temporal evolution of diffusion parameters, post-mortem conditions, and dependence on tissue structure
AU - N. Luethi
AU - F. Fritz
AU - B. Fricke
AU - J. M. Oeschger
AU - T. Streubel
AU - H. Mushumba
AU - K. Pueschel
AU - S. Mohammadi
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748254
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748254v1
AB - Purpose: Post-mortem Diffusion Magnetic Resonance Imaging (dMRI) findings on fixation-related changes in diffusion tensor imaging (DTI) parameters remain inconsistent, partly due to lower diffusion weighting and sparse early-fixation sampling. This study investigated how post-mortem tissue condition, fixation progression, and diffusion weighting shape DTI parameters in whole human brains, including whether an ex-vivo-adjusted protocol also suits in-situ and early fixation measurements. Methods: Six neurologically healthy whole human brains (post-mortem interval (PMI) 12 - 24 h) were scanned across tissue conditions, including an in-vivo reference cohort. Five brains were scanned longitudinally through immersion fixation (0 - 150 days), yielding 175 datasets with dense early sampling. Diffusion measurements at b-values 1000 - 4000 s/mm2 assessed the influence of diffusion weighting on DTI parameters. Analyses covered multiple white- and gray-matter regions and within white matter stratification by fiber orientation dispersion ({kappa}). Results: The largest mean diffusivity (MD) shift occurred between in-vivo and in-situ, whereas fractional anisotropy (FA) changed most strongly during early fixation. During immersion fixation, MD showed reproducible monoexponential saturation, while FA was heterogeneous across brains. PMI, {kappa}, and regional anatomy explained substantial FA heterogeneity across specimens. Qualitatively, the fixationrelated changes matched across diffusion weightings, but precision across specimens was highest at b-value 4000 s/mm2. Conclusion: During fixation, MD is a robust temporal marker, whereas FA requires microstructureaware interpretation. Diffusion weighting modulates how clearly fixation effects can be resolved, but the same qualitative fixation dynamics remained detectable at in-vivo-like weighting with reduced precision.
ER -