Diffusion MRI of cortical organoids reveals protocol-associated spatial reproducibility and increasing diffusivity with diffusion time
Abstract
Early human cortical development involves rapid changes in cytoarchitecture that remain difficult to interrogate non-invasively. Biophysical diffusion MRI models provide a potential window onto this microstructure, including water exchange across cell membranes, but their assumptions are difficult to validate directly in developing human tissue. Human cortical organoids provide a tractable biological model in which diffusion measurements can be related to tissue architecture within the same specimen. We scanned six fixed cortical organoids at 9.4~T, three grown under a directed and three under an undirected differentiation protocol, at three diffusion times and b-values up to 7000~s/mm2. Center-to-periphery profiles of DKI-derived diffusion metrics were reproducible across the directed organoids but more variable across the undirected organoids, while nuclear staining revealed greater variability in the internal architecture of the undirected organoids. Unexpectedly, mean diffusivity increased with diffusion time in more than 80% of tissue voxels in both batches, opposite to previous organoid measurements. Across 12,348 simulated two-compartment substrates, this increase was reproduced only with permeable membranes and an extracellular diffusivity substantially exceeding the apparent intracellular diffusivity, a regime that challenges assumptions commonly used in current gray-matter exchange models. These results support cortical organoids as biologically realistic platforms for probing early cortical microstructure and testing diffusion models under controlled conditions, while remaining amenable to post-MRI histological validation.
Related
- Test-Retest Reproducibility of Single- and Cross-Population White Matter Atlases in Diffusion MRI Tractography
- Enhanced Synaptic-Related Transcriptional Programs in Human Forebrain Organoids for Modeling Synaptopathy-Associated Neurodevelopmental Disorders
- Identification of alcohol use disorder-associated and ethanol-responsive proteins and candidate biomarkers using human cortical organoids
- Cellular and spatial context of genetic convergence between insomnia liability and DTI ALPS perivascular diffusivity
- Drying Kinetics, Apparent Moisture Diffusivity, and Energy Performance of Black Soldier Fly Larvae in a Rotating-Tray Hot-Air Dryer
BibTeX
@misc{flo2026diffusion,
title = {{Diffusion MRI of cortical organoids reveals protocol-associated spatial reproducibility and increasing diffusivity with diffusion time}},
author = {A. le Boeuf Flo and E. Taskin and O. Lavielle and A. Grigoriou and K. Pierzchala and T. P. Le and I. Jelescu and Z. Krsnik and T. Ribierre and J.-P. Thiran and J. Rafael Patino and E. J. Canales Rodriguez and E. Fischi Gomez},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755111},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755111v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Diffusion MRI of cortical organoids reveals protocol-associated spatial reproducibility and increasing diffusivity with diffusion time
AU - A. le Boeuf Flo
AU - E. Taskin
AU - O. Lavielle
AU - A. Grigoriou
AU - K. Pierzchala
AU - T. P. Le
AU - I. Jelescu
AU - Z. Krsnik
AU - T. Ribierre
AU - J.-P. Thiran
AU - J. Rafael Patino
AU - E. J. Canales Rodriguez
AU - E. Fischi Gomez
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755111
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755111v1
AB - Early human cortical development involves rapid changes in cytoarchitecture that remain difficult to interrogate non-invasively. Biophysical diffusion MRI models provide a potential window onto this microstructure, including water exchange across cell membranes, but their assumptions are difficult to validate directly in developing human tissue. Human cortical organoids provide a tractable biological model in which diffusion measurements can be related to tissue architecture within the same specimen. We scanned six fixed cortical organoids at 9.4~T, three grown under a directed and three under an undirected differentiation protocol, at three diffusion times and b-values up to 7000~s/mm^2. Center-to-periphery profiles of DKI-derived diffusion metrics were reproducible across the directed organoids but more variable across the undirected organoids, while nuclear staining revealed greater variability in the internal architecture of the undirected organoids. Unexpectedly, mean diffusivity increased with diffusion time in more than 80% of tissue voxels in both batches, opposite to previous organoid measurements. Across 12,348 simulated two-compartment substrates, this increase was reproduced only with permeable membranes and an extracellular diffusivity substantially exceeding the apparent intracellular diffusivity, a regime that challenges assumptions commonly used in current gray-matter exchange models. These results support cortical organoids as biologically realistic platforms for probing early cortical microstructure and testing diffusion models under controlled conditions, while remaining amenable to post-MRI histological validation.
ER -