E021 Bias in HD-ISS staging introduced by use of the freesurfer cross-sectional stream: insights from the Hntington’s disease young adult study (HD-YAS)
Year: 2024
Type: conference-abstract
Abstract: Background The Huntington’s Disease Integrated Staging System (HD-ISS) re-classified far-from-onset HD gene expansion carriers (GECs) as Stage 0 (without detectable pathophysiological biomarkers) and 1 (caudate and/or putamen atrophy <5th percentile in controls). These stages are likely inclusion criteria in future secondary prevention trials. The HD-ISS used the FreeSurfer (FS) longitudinal (LG) stream to define Stage 1 cut-offs, reducing within-subject variability. However, trials require application with just one MRI, necessitating cross-sectional (CS) processing. Volumetric outputs are not robust to software version and the impact of stream on volumes and Staging remains unknown. Aims To explore the effects of the CS and LG on volumes in the HD-YAS cohort. Methods T1-weighted images from 88 participants (54 GECs and 34 controls) with MRIs from visits 1 (V1) and 2 (V2) were segmented using both streams. Results Compared to the LG, the CS stream calculated: i) smaller raw caudate (-5.5% V1, -5.1% V2, both p<0.00005) and putamen (-3.2% V1, -5.0% V2, both p<0.00005), with a bias towards greater reduction for larger volumes; and ii) similar ICV (-0.2% V1, +0.3% V2, both p>0.05). This resulted in smaller adjusted caudate (-5.3% V1, -5.6% V2, both p<0.00005, without proportional bias) and putamen (-3.0% V1, -5.5% V2, both p<0.00005, with greater reduction for larger volumes). GECs shifted towards Stage 1, moving from 9 to 15/54 at V1 and 19 to 25/54 at V2 (table 1). Conclusions FreeSurfer processing stream influences HD-ISS Staging. CS stream cut-offs need to be established before applications to clinical trials.
Authors: Harry Knights, Annabelle Coleman, Nicola Hobbs, Michael Murphy, Mena Farag, Michela Leocadi, Kate Fayer, Olivia Thackeray, Douglas Langbehn, Rachael Scahill, Sarah Tabrizi, the HD-YAS Investigators
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402374656