Ex vivo mapping of the cyto- and myeloarchitecture of the human cerebral cortex using UHF MRI

Poster No:

1770 

Submission Type:

Abstract Submission 

Authors:

Raïssa Yebga Hot1,2, Alexandros Popov1,2, Justine Beaujoin1, Gaël Perez1,3, Fabrice Poupon1,2, Igor Lima Maldonado4, Jean-François Mangin1,2, Christophe Destrieux4, Cyril Poupon1,2

Institutions:

1CEA - NeuroSpin, Gif-sur-Yvette, France, 2Université Paris-Saclay, Orsay, France, 3CentraleSupélec, Gif-sur-Yvette, France, 4Université de Tours, INSERM, Imaging and Brain laboratory (iBrain), UMR 1253, Tours, France

First Author:

Raïssa Yebga Hot, PhD Student  
CEA - NeuroSpin|Université Paris-Saclay
Gif-sur-Yvette, France|Orsay, France

Co-Author(s):

Alexandros Popov  
CEA - NeuroSpin|Université Paris-Saclay
Gif-sur-Yvette, France|Orsay, France
Justine Beaujoin  
CEA - NeuroSpin
Gif-sur-Yvette, France
Gaël Perez  
CEA - NeuroSpin|CentraleSupélec
Gif-sur-Yvette, France|Gif-sur-Yvette, France
Fabrice Poupon  
CEA - NeuroSpin|Université Paris-Saclay
Gif-sur-Yvette, France|Orsay, France
Igor Lima Maldonado  
Université de Tours, INSERM, Imaging and Brain laboratory (iBrain), UMR 1253
Tours, France
Jean-François Mangin  
CEA - NeuroSpin|Université Paris-Saclay
Gif-sur-Yvette, France|Orsay, France
Christophe Destrieux  
Université de Tours, INSERM, Imaging and Brain laboratory (iBrain), UMR 1253
Tours, France
Cyril Poupon  
CEA - NeuroSpin|Université Paris-Saclay
Gif-sur-Yvette, France|Orsay, France

Introduction:

Imaging the cortical thickness has become a well-established approach to investigate neuropathologies1. Segmentation of its laminar structure at a mesoscopic scale would allow to better identify slight cortical damage in pathological cases. Since it offers improved spatial resolution and new contrast sources, ultra-high field (UHF) MRI (≥7T) is a suitable candidate to probe the cortex laminar structure2. Quantitative T1-weighted MRI related to myelination and diffusion MRI related to cytoarchitecture provide complementary insights about cortical lamination. We propose here to investigate quantitative (T1, T2, T2* and myelin water fraction (MWF)) and diffusion UHF MRI contrasts to characterize the laminar structure of the occipital cortex at the mesoscopic scale.

Methods:

Two ex vivo occipital human brain samples of both hemispheres from the same donor were scanned using two preclinical Bruker 11.7T/7T MRI systems, and 1H 60mm volume coils.
The 11.7T MRI protocol included diffusion (dMRI) and anatomical MRI datasets: a 3D T2-weighted MSME sequence (isotropic resolution 100μm; TE/TR=20/500ms), a 2D T2-weighted SE sequence (isotropic resolution 150μm; TE/TR=16/6647ms) and 3D segmented EPI PGSE sequences (isotropic resolution 200μm; TE/TR=24.3/250ms; 30 segments; δ/∆=5/12.3ms; b=1500/4500/8000s/mm²; 25/60/90 directions).
The 7T MRI protocol at 200μm isotropic resolution included a quantitative (qMRI) MRI dataset: 3D variable flip angle (VFA) FLASH sequences3 (flip angles=3-45°; 65 angles; TE/TR=4.99/15ms), a 3D T2-weighted MSME sequence (TE/TR=5.56-166.8/1000ms; 30 echoes), a 3D T2*-weighted GRE EPI sequence (TE/TR=3-69.04/9000ms; 8 echoes) and a dual flip-angle EPI B1 mapping sequence4,5(TE/TR=13.41/1500ms; flip angles=30/60°).
All data were denoised using a non-local means filter6. Quantitative T1 (qT1), T2 (qT2) and T2* (qT2*) maps were computed using a fit of the T1w and T2w signal equations. The MWF map was computed from the 7T qMRI dataset using the approach proposed in 7. Neurite density and orientation dispersion quantitative maps were computed from the 11.7T dMRI dataset using the NODDI model8. Cortices' masks were obtained from qT1 and proton density maps.
Quantitative maps were then combined using a multidimensional Gaussian mixture model to obtain clusters and their associated probability maps optimized using a Bayesian Information Criterion. Outliers were finally discarded using a Potts model.

Results:

A high SNR was obtained for both 7T and 11.7T MRI datasets presented in Figure 1. The Gennari line (layer 4b of V1 in myeloarchitectonics) is clearly visible on anatomical scans and on the qT2 map (green arrow). Subcortical white matter bundles (blue arrows) and cortical lamination are also noticeable on this map. Figure 2 depicts the segmentation of the cortex laminar structure stemming from the cyto- and myelo- Gaussian mixture models and the parameters of their distributions. 8 cyto-cluster classes and 6 myelo-cluster classes were found.
The two samples present similar contrasts and quantitative values, both being coherent with literature9,10. Differences in myelination appear within the calcarine sulcus where subclusters are found for the left hemisphere. The cyto-clustering reveals the left hemisphere displays one more layer than the right one. The latter also has an inhomogeneous spatial distribution of its cyto-clusters. As for subcortical white matter, it exhibits two contrasts on the qT2 map as presented in Figure 2, inferring a varying spatial organization for the subcortical fibers.
Supporting Image: Fig1.png
   ·Figure1. Photos of the human brain samples, images of the UHF MRI datasets and the resulting quantitative relaxometric and diffusion maps
Supporting Image: Fig2.png
   ·Figure2. The Gaussian distributions' parameters and the resulting cyto-clustering and myelo-clustering maps in the occipal cortices
 

Conclusions:

In this study, we showed that UHF qMRI and dMRI can reveal the laminar structure of two human occipital cortices by investigating their cyto- and myeloarchitectures. These results are promising and pave the way to a complete structural and quantitative mapping of the human cerebral cortex unveiling laminar features at the mesoscopic scale.

Modeling and Analysis Methods:

Segmentation and Parcellation

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Anatomy and Brain Mapping 2
Cortical Cyto- and Myeloarchitecture 1

Novel Imaging Acquisition Methods:

Multi-Modal Imaging

Keywords:

Atlasing
Cellular
Cortex
Cortical Layers
HIGH FIELD MR
MRI
Myelin
STRUCTURAL MRI

1|2Indicates the priority used for review

My abstract is being submitted as a Software Demonstration.

No

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

Other

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

Healthy subjects

Was 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.

Yes

Was 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
Diffusion MRI
Postmortem anatomy

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

7T
If Other, please list  -   11.7T

Which processing packages did you use for your study?

Other, Please list  -   Gkg Toolkit

Provide references using author date format

1. Thompson, P. M. & Toga, A. W. Cerebral Cortex Diseases and Cortical Localization. in eLS (American Cancer Society, 2003). doi:10.1038/npg.els.0002195.
2. Roebroeck, A., Miller, K. L. & Aggarwal, M. Ex vivo diffusion MRI of the human brain: Technical challenges and recent advances. NMR Biomed. 0, e3941 (2018).
3. Trzasko, J. D., Mostardi, P. M., Riederer, S. J. & Manduca, A. Estimating T1 from Multichannel Variable Flip Angle SPGR Sequences. Magn. Reson. Med. Off. J. Soc. Magn. Reson. Med. Soc. Magn. Reson. Med. 69, (2013).
4. Cunningham, C. H., Pauly, J. M. & Nayak, K. S. Saturated double-angle method for rapid B1+ mapping. Magn. Reson. Med. 55, 1326–1333 (2006).
5. Boudreau, M. et al. B1 mapping for bias-correction in quantitative T1 imaging of the brain at 3T using standard pulse sequences. J. Magn. Reson. Imaging 46, 1673–1682 (2017).
6. Buades, A., Coll, B. & Morel, J.-M. Non-Local Means Denoising. Image Process. Line 1, 208–212 (2011).
7. Kulikova, S., Hertz-Pannier, L., Dehaene-Lambertz, G., Poupon, C. & Dubois, J. A New Strategy for Fast MRI-Based Quantification of the Myelin Water Fraction: Application to Brain Imaging in Infants. PLOS ONE 11, e0163143 (2016).
8. Zhang, H., Schneider, T., Wheeler-Kingshott, C. A. & Alexander, D. C. NODDI: Practical in vivo neurite orientation dispersion and density imaging of the human brain. NeuroImage 61, 1000–1016 (2012).
9. Birkl, C. et al. Effects of formalin fixation and temperature on MR relaxation times in the human brain. NMR Biomed. 29, 458–465 (2016).
10. Sengupta, S. et al. High resolution anatomical and quantitative MRI of the entire human occipital lobe ex vivo at 9.4T. NeuroImage 168, 162–171 (2018).