Surface-based morphometry reveals caudate subnuclear structural damage in patients with premotor Huntington disease

Abstract

In patients with premotor Huntington’s disease (pmHD), literature has reported decreases in caudate volume. However, the regional vulnerability of the caudate nucleus to pmHD remains to be clarified. We aimed to determine whether regional structural damage of the caudate nucleus was present in pmHD and was correlated with clinical profile using a surface-based morphometric technique applied to T1-weighted MRI. The study cohort consisted of 14 volunteers with genetically confirmed pmHD (6 males; 41.8 ± 13.2 years) and 11 age- and sex-matched controls (5 males; 46.2 ± 11.9 years, p > 0.3). On 3-T T1-weighted images, bilateral caudate volumes were manually delineated. The resulting labels were converted to a surface, triangulated with 1002 points equally distributed across subjects using SPHARM-PDM. Displacement vectors were then computed between each individual and a template surface representing the whole cohort. Computing point-wise Jacobian determinants (JD) from these vectors quantified local volumes. We found decreases in bilateral global caudate volumes in the pmHD group compared to controls (t = 3.4; p = 0.002). Point-wise analysis of local volumes mapped caudate atrophy in pmHD primarily onto medial surface (t > 2.7; FDR < 0.05), with most pronounced changes in anteromedial subdivision. In a combined group of patients and controls, volume within the area presenting significant group difference was positively correlated with scores of executive function (r = 0.7; p < 0.001) and working memory (r = 0.6; p = 0.002). In patients, the caudate atrophy was associated with increase in disease burden (r = 0.7; p = 0.005). Caudate subnuclear atrophy measured using our surface-based morphometric technique is evident in pmHD, correlates with clinical variables, and may provide a more sensitive biomarker than global volumes.

Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes

“…The mean hippocampal volume did not differ between pmHD patients (M=3295+/−424) and controls (M=3346+/−371 mm^3), p=.8, d=.13. Shape analysis of these structures in the same sample was previously reported and revealed volume reductions from controls in the dorsal and medial portions of the caudate head (Kim et al, 2016). …”

“…To increase the automated segmentation accuracy, which can be compromised by modeling of anatomic variability, each individual image to segment was registered to images in previously described template libraries, in which 50 caudates (Kim et al, 2016) and 368 hippocampi (Kim et al, 2012) were manually labeled on these template images. These images were taken from a database comprising healthy subjects, and patients with various brain disorders and presumably have good coverage of shape variability.…”

Neuroimaging in Dementia

“…329 In a study from our center of 13 patients with pmHD and 13 age and gender-matched controls, smaller caudate volume combined with quantitative phase measurements on 7T MRI GRE sequences improved the prediction of time to disease onset (disease burden score). 331 Surface-based morphometry with 3T MRI in pmHD subjects with executive dysfunction has shown evidence of anteromedial paraventricular caudate atrophy, supporting prior neuropathological studies, 332,333 and indicating that this imaging measurement may be useful as a very early disease biomarker. In manifest (motor) stages of HD, structural MRI typically demonstrates global volume loss throughout the cerebrum, basal ganglia, brainstem, and cerebellum, 334 though the caudate, putamen, nucleus accumbens, and amygdala remain the most atrophic.…”

Longitudinal atrophy characterization of cortical and subcortical gray matter in Huntington’s disease patients

“…The TFC scale assesses daily tasks performance while UHDRS‐TMS is a clinical rating scale assessing multiple domains of motor disability (Huntington Study Group, ; Reilmann & Schubert, ). In this regard, despite previous cross‐sectional studies indicating that caudate volume decrease mainly correlates with cognitive outcomes (Harris et al, ; Kim et al, ; Rosas et al, ), other studies have reported that it also correlates with the TFC status (Rosas et al, ; Tabrizi et al, ), suggesting its influence on functionality for daily living performance. In regard to the correlation with the UHDRS‐TMS decline, cross‐sectional studies have showed that the caudate volume decrease not only correlates with the global UHDRS‐TMS score (Coppen et al, ; Galvez et al, ; Padowski et al, ; Domínguez et al, , ), but also with specific domains of this scale, including chorea degree and eye movements’ deficits (Coppen et al, ; Galvez et al, ).…”