E013 Investigating layer-specific cortical degeneration in early Huntington’s disease using 7T MRI: mechanistic insights the Huntington’s disease young adult study (HD-YAS)

<h3>Background</h3> Huntington’s Disease (HD) involves neurodegeneration beginning many years before motor disease onset, but early in-vivo insights into cortical degeneration are limited. 7T MRI has the potential to provide the increased special resolution and increased tissue contrast necessary for new insights into the underlying pathobiology of HD. <h3>Aims</h3> This study uses 7T MRI to investigate cortical layer-specific degeneration in premanifest gene expansion carriers (GECs) and explore the potential mechanistic insights these changes provide. It builds on previous work within our group demonstrating early changes versus controls in quantitative multi-parametric mapping (MPM) sequences by layer within the frontal eye fields by examining participants further from disease onset to identify if layer-specific patterns emerge earlier. <h3>Methods</h3> The HD-YAS 2.0 cohort included 126 participants (66 HD GECs, 60 controls). A subset of 20 premanifest HD GECs and 20 age- and gender-matched controls underwent 7T MRI scanning, including MP2RAGE and MPMs. <h3>Results</h3> We will present our imaging analysis pipeline methodology. Analysis of this far-from-onset cohort is ongoing. We will also present the results of our layer-specific analysis, which uses a quantitative MRI analysis to assess for groupwise differences in pre-selected regions. <h3>Conclusions</h3> 7T MRI can reveal detailed cortical layer-specific neurodegeneration in HD GECs, offering valuable mechanistic insights into the early stages of HD. This study outlines the potential of integrating advanced imaging with comprehensive clinical and biomarker data to enhance our understanding of HD pathobiology.