Brain white matter changes and their associations with non-motor dysfunction in orthostatic hypotension in α-synucleinopathy: A NODDI study.

BACKGROUND: The specific non-motor symptoms associated with α-synucleinopathies, including orthostatic hypotension (OH), cognitive impairment, and emotional abnormalities, have been a subject of ongoing controversy over the mechanisms underlying the development of a vicious cycle among them. The distinct structural alterations in white matter (WM) in patients with α-synucleinopathies experiencing OH, alongside their association with other non-motor symptoms, remain unexplored. This study employs axial diffusivity and density imaging (NODDI) to investigate WM damage specific to α-synucleinopathies with concurrent OH, delivering fresh evidence to supplement our understanding of the pathogenic mechanisms and pathological rationales behind the occurrence of a spectrum of non-motor functional impairments in α-synucleinopathies. METHODS: This study recruited 49 individuals diagnosed with α-synucleinopathies, stratified into an α-OH group (n = 24) and an α-NOH group (without OH, n = 25). Additionally, 17 healthy controls were included for supine and standing blood pressure data collection, as well as neuropsychological assessments. Magnetic resonance imaging (MRI) was utilized for the calculation of NODDI parameters, and tract-based spatial statistics (TBSS) were employed to explore differential clusters. The fibers covered by these clusters were defined as regions of interest (ROI) for the extraction of NODDI parameter values and the analysis of their correlation with neuropsychological scores. RESULTS: The TBSS analysis unveiled specific cerebral regions exhibiting disparities within the α-OH group as compared to both the α-NOH group and the healthy controls. These differences were evident in clusters that indicated a decrease in the acquisition of the neurite density index (NDI), a reduction in the orientation dispersion index (ODI), and an increase in the isotropic volume fraction (FISO) (p < 0.05). The extracted values from these ROIs demonstrated significant correlations with clinically assessed differences in supine and standing blood pressure, overall cognitive scores, and anxiety-depression ratings (p < 0.05). CONCLUSION: Patients with α-synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model, and there is a correlation with the onset and progression of non-motor functional impairments.

Aberrant microstructural integrity of white matter in mild and severe orthostatic hypotension: A NODDI study.

OBJECTIVE: Scarce evidence is available to elucidate the association between the abnormal microstructure of white matter (WM) and cognitive performance in patients with orthostatic hypotension (OH). This study investigated the microstructural integrity of WM in patients with mild OH (MOH) and severe OH (SOH) and evaluated the association of abnormal WM microstructure with the broad cognitive domains and cognition-related plasma biomarkers. METHODS: Our study included 72 non-OH (NOH), 17 MOH, and 11 SOH participants. Across the groups, the WM integrity was analyzed by neurite orientation dispersion and density imaging (NODDI), and differences in WM microstructure were evaluated by nonparametric tests and post hoc models. The correlations between WM microstructure and broad cognitive domains and cognition-related plasma biomarkers were assessed by Spearman's correlation analysis. RESULTS: The abnormal WM microstructure was localized to the WM fiber bundles in MOH patients but distributed widely in SOH cohorts (p < 0.05). Further analysis showed that the neurite density index of the left cingulate gyrus was negatively associated with amyloid ß-40, glial fibrillary acidic protein, neurofilament light chain, phospho-tau181 (p < 0.05) but positively with global cognitive function (MOCA, MMSE, AER-III), memory, attention, language, language fluency, visuospatial function and amyloid ß-40 / amyloid ß-42 (p < 0.05). Additionally, other abnormal WM microstructures of OH were associated with broad cognitive domains and cognition-related plasma biomarkers to varying degrees. CONCLUSION: The findings evidence that abnormal WM microstructures may present themselves as early as in the MOH phase and that these structural abnormalities are associated with cognitive functions and cognition-related plasma biomarkers.

Neurite orientation dispersion and density imaging in evaluation of high-grade glioma-induced corticospinal tract injury.

PURPOSE: To evaluate the application of neurite orientation dispersion and density imaging (NODDI) to brain glioma-induced corticospinal tract (CST) injury. MATERIAL AND METHODS: Twenty-four patients with high-grade glioma (HGG) in or adjacent to the CST pathway and 12 matched healthy subjects underwent structural and diffusion MRI. The CSTs were reconstructed on the both sides. The CST features including morphological features (track number, average track length and track volume) and the diffusion parameter values including fractional anisotraphy (FA), mean diffusivity (MD), intracellular volume fraction (ICVF), isotropic or free water volume fraction (ISOVF) and orientation dispersion index (ODI) along the CST were calculated. The CST features were compared between the affected and healthy side for HGG patients and between the left and right side for healthy subjects. The relative CST features were compared across the healthy subjects, patients with motor weakness and patients with normal muscle strength. Receiver operating characteristic (ROC) curve was applied to evaluate the performance of each relative CST characteristic for HGG-induced CST changes. RESULTS: Compared with the CST features on the healthy side, the track number, track volume and FA along the CST changed significantly on the affected side for HGG patients (p < 0.05 for all), whereas MD and ICVF changed significantly on the affected side only for HGG patients with motor weakness (p = 0.012 for both). In patients with motor weakness, the relative MD was significantly higher (p < 0.001), whereas the relative FA and ICVF was significantly lower (p = 0.002 and <0.001) than those in patients with normal muscle strength. The relative ICVF had a similar area under curve (AUC) to that of MD (AUC=0.953 and 0.969). Compared with the relative CST features in the healthy subjects, only the relative ICVF was significantly lower in HGG patients with normal muscle strength (p = 0.012). CONCLUSIONS: NODDI seems to be useful in reflecting the HGG infiltration to CST, and can evaluate the CST destruction with a performance similar to DTI by providing additional information about neurite density for HGG-induced CST injury.

Thalamic Structural Connectivity Abnormalities in Minimal Hepatic Encephalopathy.

Background and Aims: Numerous studies have demonstrated thalamus-related structural, functional, and metabolic abnormalities in minimal hepatic encephalopathy (MHE). We conducted the first study to investigate thalamic structural connectivity alterations in MHE. METHODS: Diffusion tensor imaging (DTI)-based probabilistic tractography was employed to determine the structural linkage between the thalamus and cortical/subcortical regions in 52 cirrhotic patients [22 with MHE; 30 without MHE (NHE)] and 30 controls. We measured these thalamic connections, which included connectivity strength (CS), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and then compared these among the three groups. Neurocognitive assessment was also performed. Correlation analysis was conducted to investigate the relationship between neurocognitive performance and the above measurements. Classification analysis was performed to determine whether thalamic connection measurements can distinguish MHE from NHE. RESULTS: The probabilistic tractography revealed thalamic structural connections, which were disrupted in cirrhotic patients (as reflected by a decrease in CS/FA and an increase in MD/AD/RD). Abnormal thalamic connections primarily involved the prefrontal cortex, sensorimotor cortex, parietal cortex, medial temporal cortex and hippocampus, and striatum. Thalamic connectivity abnormalities deteriorated from NHE to MHE, and they were correlated with patients' neurocognitive performance. The moderate classification accuracy was obtained using CS and MD as discriminating indexes. CONCLUSION: Our results demonstrated the altered thalamic structural connectivity involving both cortical and subcortical regions in MHE, which could be regarded as representative of MHE-related widespread impairments in white matter pathways. The disturbed thalamic connectivity may underlie the mechanism of cognitive deficits in MHE and may potentially be utilized as a biomarker for diagnosing MHE and in monitoring disease progression. In addition to thalamic-cortical/subcortical connections, further studies are recommended to explore the structural alterations in other white matter pathways in MHE.

Laplacian-Regularized Mean Apparent Propagator-MRI in Evaluating Corticospinal Tract Injury in Patients with Brain Glioma.

OBJECTIVE: To evaluate the application of laplacian-regularized mean apparent propagator (MAPL)-MRI to brain glioma-induced corticospinal tract (CST) injury. MATERIALS AND METHODS: This study included 20 patients with glioma adjacent to the CST pathway who had undergone structural and diffusion MRI. The entire CSTs of the affected and healthy sides were reconstructed, and the peritumoral CSTs were manually segmented. The morphological characteristics of the CST (track number, average length, volume, displacement of the affected CST) were examined and the diffusion parameter values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), mean squared displacement (MSD), q-space inverse variance (QIV), return-to-origin probability (RTOP), return-to-axis probabilities (RTAP), and return-to-plane probabilities (RTPP) along the entire and peritumoral CSTs, were calculated. The entire and peritumoral CST characteristics of the affected and healthy sides as well as those relative CST characteristics of the patients with motor weakness and normal motor function were compared. RESULTS: The track number, volume, MD, RD, MSD, QIV, RTAP, RTOP, and RTPP of the entire and peritumoral CSTs changed significantly for the affected side, whereas the AD and FA changed significantly only in the peritumoral CST (p < 0.05). In patients with motor weakness, the relative MSD of the entire CST, QIV of the entire and peritumoral CSTs, and the AD, MD, RD of the peritumoral CST were significantly higher, whereas the RTPP of the entire and peritumoral CSTs and the RTOP of the peritumoral CST were significantly lower than those in patients with normal motor function (p < 0.05 for all). In contrast, no significant changes were found in the CST morphological characteristics, FA, or RTAP (p > 0.05 for all). CONCLUSION: MAPL-MRI is an effective approach for evaluating microstructural changes after CST injury. Its sensitivity may improve when using the peritumoral CST features.

Aberrant dynamic functional network connectivity in cirrhotic patients without overt hepatic encephalopathy.

PURPOSE: Neurocognitive impairment is a common complication in cirrhosis and is associated with alterations in static functional network connectivity (FNC) between distinct brain systems. However, accumulating evidence suggests temporal variability in FNC even at rest. This study aimed to explore dynamic FNC (dFNC) differences and to elucidate their association with neurocognitive changes in cirrhotic patients. METHODS: Fifty-four cirrhotic patients and 42 controls underwent resting-state functional magnetic resonance imaging. Psychometric hepatic encephalopathy score (PHES) was used to assess neurocognitive function. Independent component analysis was performed to identify the components of seven intrinsic brain networks, including sensorimotor (SMN), auditory, visual, cognitive control (CCN), default mode (DMN), subcortical (SC), and cerebellar networks. Sliding window correlation approach was employed to calculate dFNC. FNC states were determined by k-means clustering method, and then functional state analysis was conducted to measure dynamic indices. RESULTS: The patients showed decreased dFNC in State 2, involving the connectivity between posterior subsystem of DMN and CCN (represented by bilateral insular cortex), and in State 3, involving the connectivity between SMN (represented by bilateral precentral gyrus) and SC (represented by bilateral putamen and caudate). The patients spent significantly longer time in State 4 that was with weakest FNC across all networks. We observed a significant correlation between PHES and fraction time/mean dwell time in State 4. CONCLUSIONS: Aberrant dFNC may be the underlying mechanism of neurocognitive impairments in cirrhosis. Dynamic FNC analysis may potentially be utilized in investigating cirrhosis-related neuropathological processes.