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Review
. 2021 Oct 22:12:712565.
doi: 10.3389/fneur.2021.712565. eCollection 2021.

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

Kirsi M Kinnunen  1 , Ariana P Mullin  2   3 , Dorian Pustina  4 , Emily C Turner  2 , Jackson Burton  2 , Mark F Gordon  5 , Rachael I Scahill  6 , Emily C Gantman  4 , Simon Noble  4 , Klaus Romero  2 , Nellie Georgiou-Karistianis  7 , Adam J Schwarz  8
Affiliations
Review

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

Kirsi M Kinnunen et al. Front Neurol. .

Abstract

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.

Keywords: C-Path; Huntington's disease; biomarkers; clinical trials; neurodegenerative; volumetric MRI.

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Conflict of interest statement

KMK is a full-time employee of IXICO. APM is a full-time employee of Wave Life Sciences, Ltd. DP, ECG, and SN are employed by CHDI Management to provide advisory services to CHDI Foundation. MFG is a full-time employee of Teva Pharmaceuticals. RIS provides consultancy for IXICO. AJS is a full-time employee and shareholder of Takeda Pharmaceuticals, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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