A unified imaging-histology framework for superficial white matter architecture studies in the human brain

Hwang, Y.; Rodriguez-Cruces, R.; DeKraker, J.; Cabalo, D. G.; Leppert, I. R.; Thevakumaran, R.; Tardif, C. L.; Rudko, D. A.; Paquola, C.; Bazin, P.-L.; Bernasconi, A.; Bernasconi, N.; Concha, L.; Evans, A. C.; Bernhardt, B.

doi:10.1101/2025.05.09.653169

bioRxiv · 10.1101/2025.05.09.653169

A unified imaging-histology framework for superficial white matter architecture studies in the human brain

Hwang, Y.·Rodriguez-Cruces, R.·DeKraker, J.·Cabalo, D. G.·Leppert, I. R.·Thevakumaran, R.·Tardif, C. L.·Rudko, D. A.·Paquola, C.·Bazin, P.-L.·Bernasconi, A.·Bernasconi, N.·Concha, L.·Evans, A. C.·Bernhardt, B.

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Abstract

The superficial white matter (SWM), immediately beneath the cortical mantle, is thought to play a major role in cortico-cortical connectivity as well as large-scale brain function. Yet, this compartment remains rarely studied due to its complex organization. Our objectives were to develop and disseminate a robust computational framework to study SWM organization based on 3D histology and high-field 7T MRI. Using data from the BigBrain and Ahead 3D histology initiatives, we first interrogated variations in cell staining intensities across different cortical regions and different SWM depths. These findings were then translated to in-vivo 7T quantitative myelin-sensitive MRI, including T1 relaxometry (T1 map) and magnetization transfer saturation (MTsat). As indicated by the statistical moments of the SWM intensity profiles, the first 2 mm below the cortico-subcortical boundary were characterized by high structural complexity. We quantified SWM microstructural variation using a non-linear dimensionality reduction method and examined the relationship of the resulting microstructural gradients with indices of cortical geometry, as well as structural and functional connectivity. Our results showed correlations between SWM microstructural gradients, as well as curvature and cortico-cortical functional connectivity. Our study provides novel insights into the organization of SWM in the human brain and underscores the potential of SWM mapping to advance fundamental and applied neuroscience research. HighlightsO_LIDeveloped an anatomy-based open science framework to study SWM organization based on 3D post-mortem histology and/or in-vivo high-field MRI C_LIO_LIThe first 2 mm into the white matter are characterized by high structural complexity C_LIO_LIInter-regional trends in SWM microstructural variation, which related to cortical geometry, as well as cortico-cortical connectivity C_LI

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Hwang, Y., Rodriguez-Cruces, R., DeKraker, J., Cabalo, D. G., Leppert, I. R., Thevakumaran, R., Tardif, C. L., Rudko, D. A., Paquola, C., Bazin, P.-L., Bernasconi, A., Bernasconi, N., Concha, L., Evans, A. C., Bernhardt, B.. 2025-05-10. A unified imaging-histology framework for superficial white matter architecture studies in the human brain. https://doi.org/10.1101/2025.05.09.653169

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