Table 1.
Demographic, cognitive and neuropsychiatric data of the Image-HD study participants at baseline.
Table 2.
Demographic, cognitive and neuropsychiatric data of the Image-HD participants at 18 months follow-up.
Fig 1.
Delineation of the hypothalamic region in 3T MR images based on postmortem hypothalamic material.
Overview of the boundaries to delineate the hypothalamus in postmortem human tissue applied to T1-weighted MRI acquired at 3T [13]. A-I represents the hypothalamic region in a coronal plane, from rostral to caudal direction. The red dashed lines illustrate how the hypothalamic region was delineated. Landmarks such as the hypothalamic sulcus (represented by a blue star) and the lateral or medial edge of the optical tract (represented by yellow star) were identified for the delineation and a straight line between these two points was drawn to set the superior/lateral border of the area. The optical tract was excluded in all slides. Abbreviations: optical tract, OT; fornix, F; mammillary body, MB.
Fig 2.
Discrepancy between raters when applying delineation boundaries from postmortem material to MRI.
The application of the landmarks from postmortem material to MRI resulted in discrepancy between the results obtained from the two independent raters. The difference of the mean for the hypothalamic volume in the assessed control groups was 15 ± 11% (mean ± SD) between the two raters and the intraclass correlation coefficient (ICC) between the two raters was 0.562. Upon inspection of the delineation made by the two raters, the major discrepancy was found to be when the decision was made to shift the superior/lateral border from being lateral to medial of the optical tract (A-H). Abbreviations: fornix, F; mammillary body, MB.
Fig 3.
Reproducible delineation of the hypothalamic region in 3T MR images.
Overview of the modified boundaries to delineate the hypothalamus in T1-weighted MRI acquired at 3T that yielded high reproducibility between raters (difference of the mean for the hypothalamic volume between the two raters: 2 ± 6%, ICC between the two raters = 0.937). From a rostral to caudal direction, A1-E1 column is a representative 3T MR image in a coronal plane, where the white box indicates the region of interest. Column A2-E2 represents a close up of the hypothalamic region. A schematic overview of the corresponding level adapted from Mai et al., human brain atlas [50] indicated in column A3-E3. Column A4-E4 illustrates an overlap of the schematic overview on the MR image. The red dashed lines illustrate how the hypothalamic region was delineated. Landmarks such as the hypothalamic sulcus (represented by a blue star) and the lateral edge of the optical tract (represented by yellow star) were identified for the delineation and a straight line between these two points was drawn to set the superior/lateral border of the area. The optical tract was excluded in all slides. Abbreviations: dorsomedial hypothalamic nucleus, d; fornix, F; infundibular stalk, i; lateral hypothalamus, l; mammillary body, MB; medial preoptic nucleus, m; optical tract, OT; paraventricular nucleus, P; suprachiasmatic nucleus, sc; supraoptic nucleus, s; ventromedial hypothalamic nucleus, v; tuberomammillary hypothalamic nucleus, t.
Fig 4.
Estimation of the hypothalamic volume in the IMAGE-HD cohort.
Boxplots illustrating the estimated hypothalamic volumes in control, pre-HD and symp-HD groups at baseline (A) and the 18 months follow- up time point (B). No statistical changes were observed between the groups at baseline (one-way ANOVA: group (F(2,99) = 0.484, p = 0.618) or at the 18 months follow-up time point (one-way ANOVA: group (F(2,79) = 0.067, p = 0.936).
Fig 5.
No changes in hypothalamic volume over 18 months.
Boxplots illustrating hypothalamic volume differences between the two time points for the three groups. A paired sample t-test revealed no significant changes for the hypothalamic volume between the two time points across the groups; control baseline (mean = 783 mm3, SD = 71) and control 18 months (mean = 769 mm3, SD = 65), n.s (t(24) = 0.698, p = 0.492), pre-HD baseline (mean = 763 mm3, SD = 71) and pre-HD 18 months (mean = 774 mm3, SD = 74), n.s (t(29) = −0.541, p = 0.593) and symp-HD baseline (mean = 790 mm3, SD = 85) and symp-HD 18 months (mean = 776 mm3, SD = 80), n.s (t(26) = 0.574, p = 0.571).
Fig 6.
Hypothalamic volumes corrected for ICV.
Boxplots illustrate hypothalamic volumes when corrected for ICV for the control, pre-HD and symp-HD groups at baseline. A four-way ANOVA revealed only a significant effect of ICV (ICV: F(1,96) = 16.826, p = 0.001) but not for the other parameters (group: n.s (F(2,96) = 0.597, p = 0.553), sex: F(1,96) = n.s (F = 3.804, p = 0.054), age: n.s. (F(1,96) = 0.165, p = 0.685)). Once adjusted for ICV, a three-way ANOVA was performed to assess the effect of HD gene status, sex and age on the hypothalamic volume estimates. No significant effects were found (group: n.s (F(2,92) = 0.838, p = 0.436), sex: F(1,92) = n.s (F = 0.927, p = 0.338), and age: n.s. (F(1,92) = 0.576, p = 0.564)).
Table 3.
Results from non-parametric correlation analyses for ICV-corrected hypothalamic volumes and selected clinical cognitive and neuropsychiatric data collected for all the participants in the IMAGE-HD cohort at baseline.
Table 4.
Overview of reported estimations of the hypothalamic volume in clinical studies.