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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

A standardized pipeline is presented for examining cerebellum grey matter morphometry. The pipeline combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation and voxel-based registration of the cerebellum for volumetric quantification.

Abstract

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond its historical association with motor control. Structural and functional neuroimaging studies have further refined understanding of the functional neuroanatomy of the cerebellum beyond its anatomical divisions, highlighting the need for the examination of individual cerebellar subunits in healthy variability and neurological diseases. This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification.

The pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs. The pipeline is freely available, with substantial accompanying documentation, and can be run on Mac, Windows, and Linux operating systems. The pipeline is applied in a cohort of individuals with Friedreich ataxia (FRDA), and representative results, as well as recommendations on group-level inferential statistical analyses, are provided. This pipeline could facilitate reliability and reproducibility across the field, ultimately providing a powerful methodological approach for characterizing and tracking cerebellar structural changes in neurological diseases.

Introduction

The cerebellum is a part of the brain historically associated with motor control1,2,3 and is thought to be integrally involved in only a small set of rare diseases, such as inherited ataxias4. However, converging lines of research from anatomical tracing studies in nonhuman primates, as well as human lesion and neuroimaging studies, provide compelling evidence for a role of the cerebellum in a wide array of cognitive5,6,7, affective8

Protocol

NOTE: The data used in this study were part of a project approved by the Monash University Human Research Ethics Committee (project 7810). Participants provided written informed consent. While the pipeline can be run on Mac, Windows, or Linux operating systems, ACAPULCO, SUIT, and the QC pipelines have explicitly been tested on Linux (Ubuntu) and Mac (Catalina, Big Sur v11.0.1) operating systems.

1. Module 1: ACAPULCO (anatomical parcellation)

  1. Data collection
      .......

Representative Results

Cerebellum parcellation (ACAPULCO)

Quality control of cerebellum parcellated masks:
The following examples demonstrate the ACAPULCO parcellated outputs and guide decision-making about a) the quality of the parcellated mask at the individual level and b) subsequent inclusion or exclusion of a particular lobule(s) from the statistical analyses. Ultimately, the decision to include or exclude a subject is subjective; examples of 'good parcellations,'.......

Discussion

The cerebellum is critical to a wide range of human motor3, cognitive58, affective10, and language7,59 functions and is implicated in many neurological and psychiatric diseases. The availability of a standardized and easily implementable approach for the quantification of regional cerebellar volumes will contribute to increasingly detailed 'whole-brain' structure-function mapping.......

Acknowledgements

The work presented in this manuscript was funded by an Australian National Health and Medical Research Council (NHMRC) Ideas Grant: APP1184403.

....

Materials

NameCompanyCatalog NumberComments
ACAPULCO pipeline files 0.2.1http://enigma.ini.usc.edu/protocols/imaging-protocols/Please make sure to use acapulco version 0.2.1
Docker for Machttps://docs.docker.com/desktop/mac/install/macOS must be version 10.14 or newer
Docker requires sudo priviledges
Docker imposes a memory (RAM) constraint on Mac OS. To increase the RAM, open Docker Desktop, go to Preferences and click on resources. Increase the Memory to the maximum
Docker for Windowshttps://docs.docker.com/docker-for-windows/install/
ENIGMA SUIT scriptshttp://enigma.ini.usc.edu/protocols/imaging-protocols/
FreeSurfer7https://surfer.nmr.mgh.harvard.edu/fswiki/DownloadAndInstallFollowing variables need to be set everytime you work with Freesurfer:
export FREESURFER_HOME=figure-materials-1177freesurfer _installation_directoryfigure-materials-1274
source $FREESURFER_HOME/SetUpFreeSurfer.sh
export SUBJECTS_DIR=figure-materials-1477pathfigure-materials-1544/enigma/Freesurfer
FSL (for FSLeyes). Optional6https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FslInstallation
ICV pipeline fileshttp://enigma.ini.usc.edu/protocols/imaging-protocols/ICV pipeline can be run in two ways: 1) with docker/singularity. You will not require additionl software; 2) without docker/singularity- this involves running the ICV script (calculate_icv.py) manually. You will require the following additional software:
Python version figure-materials-2193=3.5
Python module pandas
Python module fire
Python module tabulate
Python module Colorama
https://github.com/Characterisation-Virtual-Laboratory/calculate_icv
MATLAB*2019 or newerhttps://au.mathworks.com/An academic license is required
Singularity3.7 or newerhttps://www.sylabs.io/docs/Prefered for high performance computing (HPC) clusters
SPM12http://www.fil.ion.ucl.ac.uk/spm/software/spm12/Make sure spm12 and all subfolders are in your MATLAB path
SUIT Toolbox3.4http://www.diedrichsenlab.org/imaging/suit_download.htmMake sure you place SUIT toolbox in spm12/toolbox directory
Troubleshooting manual and segmentation output exampleshttp://enigma.ini.usc.edu/protocols/imaging-protocols/
Tutorial manual and videohttp://enigma.ini.usc.edu/protocols/imaging-protocols/Manual and accompanying live demonstration provide detailed step-by-step instructions on how to run the pipeline from start to finish.
*Not freely available; an academic license is required

References

  1. Holmes, G. The cerebellum of man (Hughlings Jackson memorial lecture). Brain. 62, 1-30 (1939).
  2. Ito, M. The modifiable neuronal network of the cerebellum. The Japanese Journal of Physiology. 34 (5),....

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Cerebellar Grey Matter MorphometryStructural Magnetic Resonance ImagingAnatomical ParcellationVoxel based MorphometryQuality ControlStandardized PipelineDockerSingularityMATLABSPM12AcapulcoRCIFQC ScriptsOutlier Detection

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