Bias in HD-ISS staging introduced by the FreeSurfer cross-sectional stream: Insights from the Huntington's Disease Young Adult Study (HD-YAS)

J Huntingtons Dis. 2025 Nov;14(4):396-402. doi: 10.1177/18796397251366900. Epub 2025 Aug 13.

Abstract

Huntington's Disease Integrated Staging System (HD-ISS) stages are likely inclusion criteria in future clinical trials. Stage 1 volumetric cut-offs were derived using the FreeSurfer longitudinal stream (LG). However, trials will require cross-sectional stream (CS) application with one MRI. Volumetric outputs are not robust to software type or version. T1-weighted images from 88 participants with MRIs from baseline and follow-up HD-YAS visits were segmented using both streams. CS calculated smaller caudate and putamen volumes adjusted for total intracranial volume, with greater reduction for larger volumes, shifting towards HD-ISS stage 1. CS-specific cut-offs need to be established before application to clinical trials.

Keywords: FreeSurfer; HD-ISS; MRI; caudate; huntington's disease; putamen; segmentation.

MeSH terms

  • Adult
  • Bias
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / pathology
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Humans
  • Huntington Disease* / diagnostic imaging
  • Huntington Disease* / pathology
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Putamen* / diagnostic imaging
  • Putamen* / pathology
  • Severity of Illness Index*
  • Young Adult