Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal-HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal-HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT-HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi-tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast-moving extra-cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico-striatal pathways as a function of CAG-repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG-repeats, which connects the genetic abnormality (CAG-repeats) to an imaging-based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico-striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation.

Altered isotropic volume fraction in gray matter after sleep deprivation and its association with visuospatial memory: A neurite orientation dispersion and density imaging study.

Background and aims: Diffusion magnetic resonance imaging (dMRI) studies have revealed microstructural abnormalities in white matter resulting from sleep deprivation (SD). This study aimed to adopt neurite orientation dispersion and density imaging (NODDI) to investigate the effect of SD on gray matter (GM) microstructural properties and its association to visuospatial memory (VSM). Methods: Twenty-four healthy women underwent two sessions of dMRI scanning and visuospatial ability assessment by Complex Figure Test (CFT), once during rested wakefulness (RW) and once after 24 h of SD. We calculated NODDI metrics, including intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (ISO). Differences in NODDI-related metrics between RW and SD were determined using a voxel-wise paired t-test. We identified an association between NODDI metrics and CFT results using Spearman's correlation coefficient. Results: Sleep deprivation worsened subjects' performance in the delayed-CFT trial. We observed no significant difference in ICVF and ODI between RW and SD. After SD, subjects showed decreases in ISO, primarily in the prefrontal cortex and temporal lobe, while exhibiting ISO increases in the anterior and posterior cerebellar lobe and cerebellar vermis. Furthermore, ISO change in the left superior, middle and inferior frontal gyrus was significantly correlated with completion time change in delayed-CFT trial performance. Conclusion: Our results suggested that SD hardly affected the density and spatial organization of neurites in GM, but the extra-neurite water molecule diffusion process was affected (perhaps resulting from neuroinflammation), which contributed to VSM dysfunction.

Quantitative Susceptibility Mapping and Free Water Imaging of Substantia Nigra in Parkinson's Disease.

BACKGROUND: The utility of imaging methods to detect iron content in the substantia nigra pars compacta (SNc) and free water imaging in the posterior substantia nigra (pSN) has the potential to be imaging markers for the detection of Parkinson's disease (PD). OBJECTIVE: This study aimed to compare the discriminative power of above methods, and whether the combination can improve the diagnostic potential of PD. METHODS: Quantitative susceptibility mapping (QSM) and diffusion-weighted data were obtained from 41 healthy controls (HC), 37 patients with idiopathic REM sleep behavior disorder (RBD), and 65 patients with PD. Mean QSM values of bilateral SNc and mean isotropic volume fraction (Viso) values of bilateral pSN (mean QSM|Viso values of bilateral SNc|pSN) were separately calculated and compared among the groups. RESULTS: Mean QSM|Viso values of bilateral SNc|pSN were significantly higher for RBD and PD patients compared to HC and were significantly higher in PD patients than in RBD patients. The power of the mean QSM|Viso values of bilateral SNc|pSN and combined mean QSM and Viso values was 0.873, 0.870, and 0.961 in discriminating PD and HC, 0.779, 0.719, and 0.864 in discriminating RBD from HC, 0.634, 0.636, and 0.689 in discriminating PD and RBD patients. CONCLUSION: QSM and free water imaging have similar discriminative power in the detection of prodromal and clinical PD, while combination of these two methods increases discriminative power. Our findings suggest that the combination of QSM and free water imaging has the potential to become an imaging marker for the diagnosis of PD.