Superficial White Matter Architecture in Histology and High-field MRI

Poster No:

1730 

Submission Type:

Abstract Submission 

Authors:

Youngeun Hwang1,2, Raúl Rodríguez-Cruces1,2, Jordan DeKraker1,2, Donna Gift Cabalo1,2, Ilana Leppert2, Risavarshni Thevakumaran2, Christine Tardif2, David Rudko2, Alan Evans2, Boris Bernhardt1,2

Institutions:

1Multimodal Imaging and Connectome Analysis Lab, McGill University, Montreal, Canada, 2McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, Canada

First Author:

Youngeun Hwang  
Multimodal Imaging and Connectome Analysis Lab, McGill University|McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada|Montreal, Canada

Co-Author(s):

Raúl Rodríguez-Cruces  
Multimodal Imaging and Connectome Analysis Lab, McGill University|McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada|Montreal, Canada
Jordan DeKraker, PhD  
Multimodal Imaging and Connectome Analysis Lab, McGill University|McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada|Montreal, Canada
Donna Gift Cabalo  
Multimodal Imaging and Connectome Analysis Lab, McGill University|McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada|Montreal, Canada
Ilana Leppert  
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada
Risavarshni Thevakumaran  
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada
Christine Tardif, PhD  
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada
David Rudko  
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada
Alan Evans  
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada
Boris Bernhardt  
Multimodal Imaging and Connectome Analysis Lab, McGill University|McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Montreal, Canada|Montreal, Canada

Introduction:

The superficial white matter (SWM) is a layer of white matter (WM) located immediately underneath the cortex. This SWM contains subcortical U-fibers interconnecting adjacent brain gyri, which remain incompletely myelinated until later in life. [1] Due to the key role of U-fibers in brain plasticity and aging, alterations in their density are observed in various disorders. [2,3,4] Despite its importance, the SWM has been understudied, primarily due to technical difficulties and limitations. [5] Recent advances in ultra-high field 7 Tesla (T) magnetic resonance imaging (MRI) technology have enabled precise imaging and mapping of brain microstructure, leading to reliable research on the SWM. Specifically, quantitative MRI (qMRI) could unravel complex microstructural properties by measuring diffusion MRI parameters and by quantifying changes in myelin-sensitive contrasts. In this study, we introduce an open repository [6] for sampling the SWM surfaces and demonstrate the reliability of SWM mapping using qMRI.

Methods:

Histological dataset and processing: Two post-mortem human brains were utilized in this study: (i) The 200μm BigBrain dataset, an ultra-high-resolution Merker-stained 3D histological reconstruction of a post-mortem human brain, and (ii) The 400μm AHEAD dataset, which includes multiple stainings from a post-mortem human brain. We utilized Silver (Bielschowsky) and Parvalbumin stainings from this dataset.
Multimodal MRI dataset and preprocessing: This study utilized data acquired at the Montreal Neurological Institute using a 7T Siemens Terra system. The dataset included ten healthy participants (5 females) with a mean age of 26.8±4.61 years. The following scans were acquired: (i) T1-weighted images and T1 relaxation time maps (T1 maps), (ii) Myelin-sensitive magnetization transfer (MT) ratio maps computed from gradient echo data with and without MT, and MT saturation (MTsat) maps generated using qMRLab [7] based on MT and T1-weighted images. We preprocessed all MRI data using micapipe [8].
To examine the SWM, we solved the Laplacian equation over the WM domain. This was achieved by initially computing a Laplace field across the WM and subsequently shifting an existing WM surface along that gradient. Stopping conditions were set by the geodesic distance traveled.
For the ex-vivo dataset, SWM surfaces were sampled at fifty depths, each spaced 0.06 mm apart beneath the gray-white matter interface. (Fig. 1A) In contrast, for the in-vivo dataset, SWM surfaces were sampled at fifteen depths, each separated by 0.2 mm. (Fig. 1C)
Supporting Image: Figure1.png
 

Results:

The microstructure intensity profiles within the SWM, representing the intensity values of histological and qMRI features, are shown in Fig. 1B and Fig. 1D, respectively. We then further analyzed the intensity profiles from the GM to the WM for both histology and qMRI and performed statistical analysis.(Fig. 1E) Overall, the mean intensity changes occur mainly within the first 1 mm, although the statistical measures indicate notable variation extending up to 2 mm. This suggests that beyond 2 mm, the structural complexity stabilizes, likely reflecting the presence of long fiber bundles.
To evaluate how brain geometry influences SWM intensity, we analyzed the correlation between qMRI intensity values and curvature at various SWM depths (Fig 2A). The results demonstrated a moderate correlation, leading us to generate curvature-corrected qMRI intensity maps (Fig. 2B)
Supporting Image: Figure2.png
 

Conclusions:

In this study, we investigated the microstructural intensity profiles of the SWM using histology and 7T qMRI, supported by our open repository. Our findings reveal that the deep WM interface begins approximately 2 mm below the gray-white matter boundary. By accounting for the brain geometry effect, these insights highlight the potential of SWM mapping as a valuable biomarker for advancing future research and clinical applications.

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Anatomy and Brain Mapping 1
Cortical Cyto- and Myeloarchitecture
White Matter Anatomy, Fiber Pathways and Connectivity 2

Neuroinformatics and Data Sharing:

Workflows

Novel Imaging Acquisition Methods:

Multi-Modal Imaging

Keywords:

MRI
Open-Source Code
White Matter
Other - Superficial white matter; Quantitative MRI; Multiparametric mapping

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

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Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Structural MRI
Postmortem anatomy

For human MRI, what field strength scanner do you use?

7T

Which processing packages did you use for your study?

Free Surfer
Other, Please list  -   Micapipe, Brainspace

Provide references using APA citation style.

[1] Parazzini, C., Baldoli, C., Scotti, G., & Triulzi, F. (2002). Terminal zones of myelination: MR evaluation of children aged 20-40 months. AJNR. American journal of neuroradiology, 23(10), 1669–1673.
[2] Zikopoulos, B., & Barbas, H. (2010). Changes in prefrontal axons may disrupt the network in autism. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30(44), 14595–14609. https://doi.org/10.1523/JNEUROSCI.2257-10.2010
[3] Liu, M., Bernhardt, B. C., Hong, S. J., Caldairou, B., Bernasconi, A., & Bernasconi, N. (2016). The superficial white matter in temporal lobe epilepsy: a key link between structural and functional network disruptions. Brain : a journal of neurology, 139(Pt 9), 2431–2440. https://doi.org/10.1093/brain/aww167
[4] Carmeli, C., Fornari, E., Jalili, M., Meuli, R., & Knyazeva, M. G. (2014). Structural covariance of superficial white matter in mild Alzheimer's disease compared to normal aging. Brain and behavior, 4(5), 721–737. https://doi.org/10.1002/brb3.252
[5] Kirilina, E., Helbling, S., Morawski, M., Pine, K., Reimann, K., Jankuhn, S., Dinse, J., Deistung, A., Reichenbach, J. R., Trampel, R., Geyer, S., Müller, L., Jakubowski, N., Arendt, T., Bazin, P. L., & Weiskopf, N. (2020). Superficial white matter imaging: Contrast mechanisms and whole-brain in vivo mapping. Science advances, 6(41), eaaz9281. https://doi.org/10.1126/sciadv.aaz9281
[6] DeKraker, J., Cruces, R., & Hwang, Y. (2024). Superficial White Matter. Zenodo. https://doi.org/10.5281/zenodo.11510179
[7] Karakuzu A., Boudreau M., Duval T.,Boshkovski T., Leppert I.R., Cabana J.F., Gagnon I., Beliveau P., Pike G.B., Cohen-Adad J., Stikov N. (2020), qMRLab: Quantitative MRI analysis, under one umbrella doi: 10.21105/joss.02343
[8] Cruces, R. R., Royer, J., Herholz, P., Larivière, S., Vos de Wael, R., Paquola, C., Benkarim, O., Park, B. Y., Degré-Pelletier, J., Nelson, M. C., DeKraker, J., Leppert, I. R., Tardif, C., Poline, J. B., Concha, L., & Bernhardt, B. C. (2022). Micapipe: A pipeline for multimodal neuroimaging and connectome analysis. NeuroImage, 263, 119612. https://doi.org/10.1016/j.neuroimage.2022.119612

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