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)

<h3>Background</h3> 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 &lt;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. <h3>Aims</h3> To explore the effects of the CS and LG on volumes in the HD-YAS cohort. <h3>Methods</h3> 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. <h3>Results</h3> Compared to the LG, the CS stream calculated: i) smaller raw caudate (-5.5% V1, -5.1% V2, both p&lt;0.00005) and putamen (-3.2% V1, -5.0% V2, both p&lt;0.00005), with a bias towards greater reduction for larger volumes; and ii) similar ICV (-0.2% V1, +0.3% V2, both p&gt;0.05). This resulted in smaller adjusted caudate (-5.3% V1, -5.6% V2, both p&lt;0.00005, without proportional bias) and putamen (-3.0% V1, -5.5% V2, both p&lt;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). <h3>Conclusions</h3> FreeSurfer processing stream influences HD-ISS Staging. CS stream cut-offs need to be established before applications to clinical trials.