Objective: To compare the sensitivity of ¹¹C‑UCB‑J PET, ¹⁸F-FDG PET and volumetric MRI for detection of longitudinal brain changes in early Huntington’s Disease (HD).

Background: Development of disease-modifying treatments for HD could be aided by the use of imaging biomarkers of disease progression. Volumetric MRI and ¹⁸F-FDG PET previously showed longitudinal brain changes in early HD. Cross-sectional PET with ¹¹C‑UCB‑J, a radioligand for the brain-wide presynaptic terminal marker SV2A, revealed widespread presynaptic terminal damage in early HD, but longitudinal ¹¹C‑UCB‑J PET data in HD have not been reported.

Method: Seventeen HD mutation carriers (6 premanifest and 11 early manifest) and 13 healthy controls underwent clinical assessments, ¹¹C‑UCB‑J PET, ¹⁸F‑FDG PET and volumetric MRI at baseline (BL) and after 21.4 ± 2.7 months (Y2). Volumes of interest were delineated based on individual 3D T1 MRI. ¹¹C-UCB-J SUVR‑1 and ¹⁸F-FDG relative metabolism parametric images were calculated with centrum semiovale and pons respectively. PET data were corrected for partial volume effects. Within-group and between-group longitudinal clinical and imaging changes were assessed. Correlations between longitudinal clinical changes and imaging data were calculated.

Results: The HD group showed significant 2-year worsening of UHDRS motor scores. There was significant longitudinal volume loss within the HD group in caudate (-4.5 ± 3.8 %), putamen (-3.6 ± 3.5 %), pallidum (-3.0 ± 2.7 %), and frontal cortex (-2.0 ± 2.1 %) (all p < 0.001). Within the HD group there was longitudinal loss of putaminal SV2A binding (-6.4 ± 8.8 %, p = 0.01) and putaminal glucose metabolism (-2.8 ± 4.4 %, p = 0.008), but these changes were not significant after correction for multiple comparisons. The premanifest subgroup at BL only had significantly lower SV2A binding than controls in basal ganglia structures, but at Y2 additionally had significant SV2A loss in frontal and parietal cortex, indicating spread of SV2A loss from subcortical to cortical regions. In the total HD group longitudinal motor change correlated with BL putaminal volume and glucose metabolism.

Conclusion: Volumetric MRI is more sensitive than ¹¹C‑UCB‑J PET and ¹⁸F‑FDG PET for detection of 2-year brain changes in early HD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-imaging-of-regional-volumes-presynaptic-terminals-and-glucose-metabolism-in-brains-of-people-with-early-huntingtons-disease/