Recommendations to Optimize the Use of Volumetric MRI in Huntington's Disease Clinical Trials

Kirsi M. Kinnunen, Ariana P. Mullin, Dorian Pustina, Emily C. Turner, Jackson Burton, Mark F. Gordon, Rachael I. Scahill, Emily C. Gantman, Simon Noble, Klaus Romero, Nellie Georgiou-Karistianis, Adam J. Schwarz, on behalf of the Huntington’s Disease Regulatory Science Consortium (HD-RSC)

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Volumetric magnetic resonance imaging (vMRI) has been widely studied in Huntington's disease (HD) and is commonly used to assess treatment effects on brain atrophy in interventional trials. Global and regional trajectories of brain atrophy in HD, with early involvement of striatal regions, are becoming increasingly understood. However, there remains heterogeneity in the methods used and a lack of widely-accessible multisite, longitudinal, normative datasets in HD. Consensus for standardized practices for data acquisition, analysis, sharing, and reporting will strengthen the interpretation of vMRI results and facilitate their adoption as part of a pathobiological disease staging system. The Huntington's Disease Regulatory Science Consortium (HD-RSC) currently comprises 37 member organizations and is dedicated to building a regulatory science strategy to expedite the approval of HD therapeutics. Here, we propose four recommendations to address vMRI standardization in HD research: (1) a checklist of standardized practices for the use of vMRI in clinical research and for reporting results; (2) targeted research projects to evaluate advanced vMRI methodologies in HD; (3) the definition of standard MRI-based anatomical boundaries for key brain structures in HD, plus the creation of a standard reference dataset to benchmark vMRI data analysis methods; and (4) broad access to raw images and derived data from both observational studies and interventional trials, coded to protect participant identity. In concert, these recommendations will enable a better understanding of disease progression and increase confidence in the use of vMRI for drug development.

Original languageEnglish
Article number712565
Number of pages10
JournalFrontiers in Neurology
Publication statusPublished - 22 Oct 2021


  • biomarkers
  • C-Path
  • clinical trials
  • Huntington's disease
  • neurodegenerative
  • volumetric MRI

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