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Neurodegeneration
Research paper
Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS
  1. Rebecca J Broad1,2,
  2. Matt C Gabel1,
  3. Nicholas G Dowell1,
  4. David J Schwartzman3,
  5. Anil K Seth3,
  6. Hui Zhang4,
  7. Daniel C Alexander4,
  8. Mara Cercignani1,5,
  9. P Nigel Leigh1,2
  1. 1 Department of Neuroscience, Trafford Centre for Biomedical Research, Brighton and Sussex Medical School, Brighton, UK
  2. 2 Brighton and Sussex University Hospitals NHS Trust, Princess Royal Hospital, Haywards Heath, UK
  3. 3 Sackler Centre Consciousness Science, University of Sussex, Brighton, UK
  4. 4 Centre for Medical Image Computing and Department of Computer Science, University College London, London, UK
  5. 5 Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy
  1. Correspondence to Dr Rebecca J Broad, Trafford Centre for Medical Research, Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9RY, UK; r.broad{at}bsms.ac.uk

Abstract

Background Corticospinal tract (CST) degeneration and cortical atrophy are consistent features of amyotrophic lateral sclerosis (ALS). We hypothesised that neurite orientation dispersion and density imaging (NODDI), a multicompartment model of diffusion MRI, would reveal microstructural changes associated with ALS within the CST and precentral gyrus (PCG) ‘in vivo’.

Methods 23 participants with sporadic ALS and 23 healthy controls underwent diffusion MRI. Neurite density index (NDI), orientation dispersion index (ODI) and free water fraction (isotropic compartment (ISO)) were derived. Whole brain voxel-wise analysis was performed to assess for group differences. Standard diffusion tensor imaging (DTI) parameters were computed for comparison. Subgroup analysis was performed to investigate for NODDI parameter differences relating to bulbar involvement. Correlation of NODDI parameters with clinical variables were also explored. The results were accepted as significant where p<0.05 after family-wise error correction at the cluster level, clusters formed with p<0.001.

Results In the ALS group NDI was reduced in the extensive regions of the CST, the corpus callosum and the right PCG. ODI was reduced in the right anterior internal capsule and the right PCG. Significant differences in NDI were detected between subgroups stratified according to the presence or absence of bulbar involvement. ODI and ISO correlated with disease duration.

Conclusions NODDI demonstrates that axonal loss within the CST is a core feature of degeneration in ALS. This is the main factor contributing to the altered diffusivity profile detected using DTI. NODDI also identified dendritic alterations within the PCG, suggesting microstructural cortical dendritic changes occur together with CST axonal damage.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jnnp-2018-318830

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    Footnotes

    • Contributors As clinical research fellow, RJB recruited and consented participants, performed all clinical assessments, supervised imaging, and processed and interpreted the data. RJB also constructed the first draft of this article and prepared all of the figures. MCG performed the data preprocessing and advised on statistical analysis. NGD designed the NODDI pipeline for the institution and provided supervision to RJB and MCG in data preprocessing. DJS, AKS, HZ and DCA contributed to the design of the study and contributed to the drafting of the paper. HZ and DCA provided the necessary skills underpinning NODDI, advised on the development of the hypothesis and contributed to writing the funding proposal. They also advised on data interpretation and on all drafts of the paper. MC contributed to the design of the study, and to developing and submitting the funding proposal, and designed and implemented the imaging protocol. MC also provided supervision for the data processing and analysis, and revised the drafts of the paper at all stages. PNL was chief investigator for this study. PNL screened the subjects with ALS recruited through the Sussex ALS clinical service. PNL and MC conceived the hypotheses and submitted the funding proposal, supervised the clinical research fellow (RJB) and oversaw all aspects of the study including ethics and research governance. PNL edited and revised the drafts of the paper at all stages. All authors reviewed and accepted the final manuscript.

    • Funding This study was supported by a grant from the Motor Neurone Disease Association of England and Northern Ireland (Reference: Leigh/Apr14/824/791). EPSRC grants N018702 and M020533 support DCA's work on this topic.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval Favourable ethical opinion was awarded by the National Health Service Research Ethics Committee London (14/LO/0195).

    • Provenance and peer review Not commissioned; externally peer reviewed.