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Functional 7T MRI analyses reveal altered cerebellar activity and connectivity in multiple sclerosis

Poster No:

181 

Submission Type:

Abstract Submission 

Authors:

Myrte Strik1,2,3, Emma Brouwer1,2, Nikos Priovoulos1,2,4, Renan Mukerjee1, Mark Wessels5, Eva Strijbis5, Frederik Barkhof6,7, Menno Schoonheim3, Wietske van der Zwaag1,2

Institutions:

1Spinoza Centre for Neuroimaging, Amsterdam, Netherlands, 2Computational Cognitive Neuroscience and Neuroimaging, Netherlands Institute for Neuroscience, Royal Netherlands Academy for Arts and Sciences (KNAW), Amsterdam, Netherlands, 3Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, 4Department of Biomedical Engineering and Physics, Amsterdam UMC, Amsterdam, Netherlands, 5Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, 6Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, 7UCL Institutes of Neurology and Healthcare Engineering, London, United Kingdom

First Author:

Myrte Strik  
Spinoza Centre for Neuroimaging|Computational Cognitive Neuroscience and Neuroimaging, Netherlands Institute for Neuroscience, Royal Netherlands Academy for Arts and Sciences (KNAW)|Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam
Amsterdam, Netherlands|Amsterdam, Netherlands|Amsterdam, Netherlands

Co-Author(s):

Emma Brouwer  
Spinoza Centre for Neuroimaging|Computational Cognitive Neuroscience and Neuroimaging, Netherlands Institute for Neuroscience, Royal Netherlands Academy for Arts and Sciences (KNAW)
Amsterdam, Netherlands|Amsterdam, Netherlands
Nikos Priovoulos  
Spinoza Centre for Neuroimaging|Computational Cognitive Neuroscience and Neuroimaging, Netherlands Institute for Neuroscience, Royal Netherlands Academy for Arts and Sciences (KNAW)|Department of Biomedical Engineering and Physics, Amsterdam UMC
Amsterdam, Netherlands|Amsterdam, Netherlands|Amsterdam, Netherlands
Renan Mukerjee  
Spinoza Centre for Neuroimaging
Amsterdam, Netherlands
Mark Wessels  
Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam
Amsterdam, Netherlands
Eva Strijbis  
Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam
Amsterdam, Netherlands
Frederik Barkhof, MD, Ph. D  
Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam|UCL Institutes of Neurology and Healthcare Engineering
Amsterdam, Netherlands|London, United Kingdom
Menno Schoonheim  
Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam
Amsterdam, Netherlands
Wietske van der Zwaag  
Spinoza Centre for Neuroimaging|Computational Cognitive Neuroscience and Neuroimaging, Netherlands Institute for Neuroscience, Royal Netherlands Academy for Arts and Sciences (KNAW)
Amsterdam, Netherlands|Amsterdam, Netherlands
E-Poster

Introduction:

The cerebellum is a small but finely organized region, highly connected and integrated in major brain networks involved in cognition and motor control.(1) In multiple sclerosis (MS), these functions are often affected, and the cerebellum is a prevalent injury site.(2) Despite the clinical importance and interest, the cerebellum is often overlooked due to technical challenges in imaging its thin and highly folded cortex. As such, the functional involvement of the cerebellum in MS is currently understudied and likely underestimated.

Previous functional MRI studies shown altered network connectivity(3,4) and task-based activation(5) in MS, but primarily focused on the cerebrum, and cerebellar results often lack specificity. To image the cerebellum in greater detail, 7T MRI can be valuable due to the higher signal-to-noise ratio and increased spatial and temporal resolutions compared to clinical field strengths. Using 7T, a somatotopic organization has been mapped in anterior and posterior cerebellar lobules,(6) yet it's unclear whether this is altered in MS. In this preliminary study, we investigated cerebellar motor task responses and resting-state connectivity disturbances in people with MS and controls using 7T fMRI and submillimetre resolution anatomical images.

Methods:

Six people with MS with signs of cerebellar damage (2 females, age=54±9 years) and 3 healthy controls (HC) (1 female, age=57±14 years) were scanned using a 7T-Phillips MRI-scanner (8Tx/32Rx whole-head coil). For the flexing motor task (10s-ON, 10s-OFF, 5min) and resting-state scan (fixation on cross, 7min), a 3D-EPI slab covering the cerebellum was used (1mm-isotropic, TR/TE=3288ms/21ms, SENSE=2.6/3.27-AP/RL, FOV=192x60x192mm3, α=20°). Anatomical imaging included: whole-brain 1mm-isotropic MP2RAGE (TR/TE=2.3ms/6.2ms, TI1/TI2=800/2700, TRvolume=5500ms, α=7°/5°, FOV=230x230x185)(7) and a submillimeter whole-cerebellar image (0.4mm isotropic) with prospective motion correction (5.65/1.88; TI1/TI2, 1000ms/2900ms; TI1/TI2, α =7°/5, FOV=210×120×60mm3, sensitivity encoding y/z, 1.5/1) (more details (8)). Motion correction involved real-time FOV updates by realignment of reconstructed fat navigators (3D EPI; 2mm; fat-selective binomial excitation pulse; 5.65/1.88; Tvol=550ms; α=1°; sensitivity encoding y/z, 4/2; Tacq=0.55s, FOV=240×240×120mm3). Functional data was motion/distortion-corrected and 0.4mm cerebellar anatomical images were denoised using a spatially adapted filter.(9) For the motor task, a first level GLM (FSL, flex>rest, Z>3.1, p<0.05) was used. A cerebellar motor function mask(10) was warped into each participant's anatomical space and manually divided to identify four relevant regions of interest (ROIs) (Fig1-A). To investigate cerebellar connectivity, a spherical seed mask (radius=4px) was generated from the highest motor task Z-score voxel (Fig-2-A), from which mean time-courses were extracted and used as first level GLM input (motor-seed>rest, Z>3.1, p<0.05).

Results:

Flexing of the hand resulted in significant (Z>3.1, p<0.05) bilateral cerebellar activation in both anterior and posterior ROIs for all HCs, contrary to less than 50% of MS patients (Fig-1B/C). Maximum Z-scores were lower in MS (Right Anterior: MED=4.28±2.07, Posterior: MED=4.22±1.08) compared to HC (Right Anterior: MED=7.85±0.5, Posterior: MED=5.37±0.62). All participants had significant (Z>3.1, p<0.05) RS connectivity within cerebellar parts of the motor network (Fig2-B/C). Compared to HC, MS patients had lower average RS connectivity Z-scores (Fig-2B).
Supporting Image: Figure1.png
Supporting Image: Figure2.png
 

Conclusions:

We studied the communication and mapped regional activation during movements and preliminary results indicate lower and inconsistent cerebellar task-based activation, as well as lower resting-state connectivity in MS. Future investigations will involve a larger cohort and a more in-depth to confirm findings and identify subject specific differences in cerebellar motor network activity and connectivity.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1

Modeling and Analysis Methods:

Activation (eg. BOLD task-fMRI) 2
Connectivity (eg. functional, effective, structural)
Task-Independent and Resting-State Analysis

Keywords:

Acquisition
Cerebellum
Degenerative Disease
DISORDERS
FUNCTIONAL MRI
HIGH FIELD MR
Motor
MRI
Neurological
STRUCTURAL MRI

1|2Indicates the priority used for review

Provide references using author date format

1. Buckner RL, Krienen FM, Castellanos A, Diaz JC, Thomas Yeo BT. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol [Internet]. 2011 Nov [cited 2023 Jul 20];106(5):2322. Available from: /pmc/articles/PMC3214121/
2. Weissert R, Ayache SS, Bauer J, Wilkins A. Cerebellar Dysfunction in Multiple Sclerosis. Cerebellar Dysfunction in Multiple Sclerosis Front Neurol [Internet]. 2017 [cited 2023 Oct 31];8:312. Available from: www.frontiersin.org
3. Meijer KA, Eijlers AJC, Douw L, Uitdehaag BMJ, Barkhof F, Geurts JJG, et al. Increased connectivity of hub networks and cognitive impairment in multiple sclerosis. Neurology. 2017;
4. Strik M, Eijlers AJC, Dekker I, Broeders TAA, Douw L, Killestein J, et al. Sensorimotor network dynamics predict decline in upper and lower limb function in people with multiple sclerosis. Multiple Sclerosis Journal [Internet]. 2023 Jan 1 [cited 2023 Nov 29];29(1):81–91. Available from: https://journals.sagepub.com/doi/full/10.1177/13524585221125372
5. Rocca MA, Colombo B, Falini A, Ghezzi A, Martinelli V, Scotti G, et al. Cortical adaptation in patients with MS: A cross-sectional functional MRI study of disease phenotypes. Lancet Neurology. 2005;4(10):618–26.
6. Boillat Y, Bazin PL, Van Der Zwaag W. Whole-body somatotopic maps in the cerebellum revealed with 7T fMRI. 2020 [cited 2023 Nov 27]; Available from: https://doi.org/10.1016/j.neuroimage.2020.116624
7. Marques JP, Kober T, Krueger G, van der Zwaag W, Van de Moortele PF, Gruetter R. MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field. Neuroimage. 2010 Jan 15;49(2):1271–81.
8. Priovoulos N, Andersen M, Dumoulin SO, Boer VO, van der Zwaag W. High-Resolution Motion-corrected 7.0-T MRI to Derive Morphologic Measures from the Human Cerebellum in Vivo. Radiology. 2023 Apr 1;307(2).
9. Tustison NJ, Avants BB, Cook PA, Zheng Y, Egan A, Yushkevich PA, et al. N4ITK: Improved N3 Bias Correction. IEEE Trans Med Imaging [Internet]. 2010 Jun [cited 2023 Nov 27];29(6):1310. Available from: /pmc/articles/PMC3071855/
10. King M, Hernandez-Castillo CR, Poldrack RA, Ivry RB, Diedrichsen J. Functional boundaries in the human cerebellum revealed by a multi-domain task battery. Nature Neuroscience 2019 22:8 [Internet]. 2019 Jul 8 [cited 2023 Oct 26];22(8):1371–8. Available from: https://www.nature.com/articles/s41593-019-0436-x