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Volumetric Analysis of the Hypothalamus in Huntington Disease Using 3T MRI: The IMAGE-HD Study

Gabery S1, Georgiou-Karistianis N2, Lundh SH1, Cheong RY1, Churchyard A3, Chua P4, Stout JC2, Egan GF5, Kirik D6 and Petersén Å1.

1Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
2School of Psychological Sciences, Monash University, Clayton, Victoria, 3180, Australia.
3School of Psychological Sciences, Monash University, Clayton, Victoria, 3180, Australia; Huntington's Disease Unit, Bethlehem Hospital, Kooyong Rd, Caulfield, Victoria, 3162, Australia.
4Huntington's Disease Unit, Bethlehem Hospital, Kooyong Rd, Caulfield, Victoria, 3162, Australia; Department of Psychiatry, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, 3168, Australia.
5School of Psychological Sciences, Monash University, Clayton, Victoria, 3180, Australia; Monash Biomedical Imaging (MBI), Monash University, Clayton, Victoria, 3180, Australia; Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative (VLSCI), Melbourne, Victoria, Australia.
6Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S) Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden; Lund University Bioimaging Center, Lund, Sweden.

PLoS One 10(2) (2015)

Abstract

Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Non-motor symptoms and signs such as psychiatric disturbances, sleep problems and metabolic dysfunction are part of the disease manifestation. These aspects may relate to changes in the hypothalamus, an area of the brain involved in the regulation of emotion, sleep and metabolism. Neuropathological and imaging studies using both voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) as well as positron emission tomography (PET) have demonstrated pathological changes in the hypothalamic region during early stages in symptomatic HD. In this investigation, we aimed to establish a robust method for measurements of the hypothalamic volume in MRI in order to determine whether the hypothalamic dysfunction in HD is associated with the volume of this region. Using T1-weighted imaging, we describe a reproducible delineation procedure to estimate the hypothalamic volume which was based on the same landmarks used in histologically processed postmortem hypothalamic tissue. Participants included 36 prodromal HD (pre-HD), 33 symptomatic HD (symp-HD) and 33 control participants who underwent MRI scanning at baseline and 18 months follow-up as part of the IMAGE-HD study. We found no evidence of cross-sectional or longitudinal changes between groups in hypothalamic volume. Our results suggest that hypothalamic pathology in HD is not associated with volume changes.