Neurite orientation dispersion and density imaging quantifies microstructural impairment in the thalamus and its connectivity in amyotrophic lateral sclerosis.

AIMS: To evaluate microstructural impairment in the thalamus and thalamocortical connectivity using neurite orientation dispersion and density imaging (NODDI) in amyotrophic lateral sclerosis (ALS). METHODS: This study included 47 healthy controls and 43 ALS patients, whose structural and diffusion-weighted data were collected. We used state-of-the-art parallel transport tractography to identify thalamocortical pathways in individual spaces. Thalamus was then parcellated into six subregions based on its connectivity pattern with the priori defined cortical (i.e., prefrontal/motor/somatosensory/temporal/posterior-parietal/occipital) regions. For each of the thalamic and cortical subregions and thalamo-cortical tracts, we compared the following NODDI metrics between groups: orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (ISO). We also used these metrics to conduct receiver operating characteristic curve (ROC) analyses and Spearman correlation. RESULTS: In ALS patients, we found decreased ODI and increased ISO in the thalamic subregion connecting the left motor cortex and other extramotor (e.g., somatosensory and occipital) cortex (Bonferroni-corrected p < 0.05). NDI decreased in the bilateral thalamo-motor and thalamo-somatosensory tracts and in the right thalamo-posterior-parietal and thalamo-occipital tracts (Bonferroni-corrected p < 0.05). NDI reduction in the bilateral thalamo-motor tract (p = 0.017 and 0.009) and left thalamo-somatosensory tract (p = 0.029) was correlated with disease severity. In thalamo-cortical tracts, NDI yielded a higher effect size during between-group comparisons and a greater area under ROC (p < 0.05) compared with conventional diffusion tensor imaging metrics. CONCLUSIONS: Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo-cortical connectivity in ALS.

Corticospinal fibers with different origins impair in amyotrophic lateral sclerosis: A neurite orientation dispersion and density imaging study.

AIMS: To investigate microstructural impairments of corticospinal tracts (CSTs) with different origins in amyotrophic lateral sclerosis (ALS) using neurite orientation dispersion and density imaging (NODDI). METHODS: Diffusion-weighted imaging data acquired from 39 patients with ALS and 50 controls were used to estimate NODDI and diffusion tensor imaging (DTI) models. Fine maps of CST subfibers originating from the primary motor area (M1), premotor cortex, primary sensory area, and supplementary motor area (SMA) were segmented. NODDI metrics (neurite density index [NDI] and orientation dispersion index [ODI]) and DTI metrics (fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) were computed. RESULTS: The patients with ALS showed microstructural impairments (reflected by NDI, ODI, and FA reductions and MD, AD, and RD increases) in CST subfibers, especially in M1 fibers, which correlated with disease severity. Compared with other diffusion metrics, NDI yielded a higher effect size and detected the greatest extent of CST subfibers damage. Logistic regression analyses based on NDI in M1 subfiber yielded the best diagnostic performance compared with other subfibers and the whole CST. CONCLUSIONS: Microstructural impairment of CST subfibers (especially those originating from M1) is the key feature of ALS. The combination of NODDI and CST subfibers analysis may improve diagnosing performance for ALS.

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.

Metabolic alterations in the right anterior insula among patients with cirrhosis without overt hepatic encephalopathy: a magnetic resonance spectroscopy study.

Purpose: We investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction. Methods: In this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. 1H-magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann-Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses. Results: Patients with cirrhosis performed worse on PHES in comparison with HCs (P < 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 ± 0.07 vs. 0.74 ± 0.19, P = 0.025) and increased Glx/tCr (1.79 ± 0.17 vs. 2.07 ± 0.29, P < 0.001) in the rAI. We did not observe any significant between-group differences in tCho/tCr and NAA/tCr. The blood ammonia level was correlated with Glx/tCr (r = 0.405, P = 0.022) and mI/tCr (r = -0.398, P = 0.024) of the rAI. In addition, PHES was negatively correlated with Glx/tCr of the rAI (r = -0.379, P = 0.033). Conclusion: Metabolic disturbance of the rAI, which is associated with ammonia intoxication, might account for the neural substrate of cirrhosis-related cognitive dysfunction to some extent.

Altered stability of brain functional architecture after sleep deprivation: A resting-state functional magnetic resonance imaging study.

Background and aims: Resting-state functional magnetic resonance imaging (fMRI) studies using static and dynamic functional connectivity (FC) approaches have revealed brain dysfunction resulting from sleep deprivation (SD). The effects of SD on the stability of brain functional architecture remain unclear. This study investigated the functional stability (FS) changes induced by SD and its association with neurocognitive alterations. Materials and methods: In this study, we recruited 24 healthy women. All participants underwent two sessions of resting-state fMRI scanning and neurocognitive assessment. The assessments included the Digit Symbol Test, Digit Span Test, Trail-Making Test (TMT), and Complex Figure Test (CFT). Participants completed one session under rested wakefulness (RW) and one session after SD for 24 h. To estimate dynamic FC, we used the sliding window approach; and then, to characterize the FS of each voxel, we measured dynamic FC concordance over time. We used a paired t-test to identify differences in FS between RW and SD. To examine the relationship between these changes in FS and alterations in neurocognitive performance, we conducted Spearman's correlation analyses. Results: SD affected the performance of the Digit Symbol Test, Digit Span Test, and CFT. Compared with RW, subjects with SD exhibited decreased FS in the bilateral anterior and posterior cingulate gyrus and medial frontal gyrus, right superior frontal gyrus, and cerebellum posterior lobe, while they exhibited increased FS in the bilateral precentral/postcentral gyrus and supplementary motor area, right parahippocampal gyrus and fusiform gyrus, left inferior occipital gyrus, and bilateral cerebellum anterior lobe. After SD, FS changes in the right parahippocampal gyrus and fusiform gyrus were correlated with altered performance in the Digit Symbol Test and CFT. Conclusion: Our findings showed that the stability of the brain's functional architecture could be altered by SD. This stability alteration may correspond to multiple neurocognitive domain changes.

Characterizing Sensorimotor-Related Area Abnormalities in Amyotrophic Lateral Sclerosis: An Intravoxel Incoherent Motion Magnetic Resonance Imaging Study.

RATIONALE AND OBJECTIVES: To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. MATERIALS AND METHODS: IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. RESULTS: ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). CONCLUSION: These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

Dynamic Changes in Functional Network Connectivity Involving Amyotrophic Lateral Sclerosis and Its Correlation With Disease Severity.

BACKGROUND: Aberrant static functional connectivity (FC) has been well demonstrated in amyotrophic lateral sclerosis (ALS); however, ALS-related alterations in FC dynamic properties remain unclear, although dynamic FC analyses contribute to uncover mechanisms underlying neurodegenerative disorders. PURPOSE: To explore dynamic functional network connectivity (dFNC) in ALS and its correlation with disease severity. STUDY TYPE: Prospective. SUBJECTS: Thirty-two ALS patients and 45 healthy controls. FIELD STRENGTH/SEQUENCE: Multiband resting-state functional images using gradient echo echo-planar imaging and T1-weighted images were acquired at 3.0 T. ASSESSMENT: Disease severity was evaluated with the revised ALS Functional Rating Scale (ALSFRS-R) and patients were stratified according to diagnostic category. Independent component analysis was conducted to identify the components of seven intrinsic brain networks (ie, visual/sensorimotor (SMN)/auditory/cognitive-control (CCN)/default-mode (DMN)/subcortical/cerebellar networks). A sliding-window correlation approach was used to compute dFNC. FNC states were determined by k-mean clustering, and state-specific FNC and dynamic indices (fraction time/mean dwell time/transition number) were calculated. STATISTICAL TESTS: Two-sample t test used for comparisons on dynamic measures and Spearman's correlation analysis. RESULTS: ALS patients showed increased FNC between DMN-SMN in state 1 and between CCN-SMN in state 4. Patients remained in state 2 (showing the weakest FNC) for a significantly longer time (mean dwell time: 49.8 ± 40.1 vs. 93.6 ± 126.3; P < 0.05) and remained in state 1 (showing a relatively strong FNC) for a shorter time (fraction time: 0.27 ± 0.25 vs. 0.13 ± 0.20; P < 0.05). ALS patients exhibited less temporal variability in their FNC (transition number: 10.2 ± 4.4 vs. 7.8 ± 3.8; P < 0.05). A significant correlation was observed between ALSFRS-R and mean dwell time in state 2 (r = -0.414, P < 0.05) and transition number (r = 0.452, P < 0.05). No significant between-subgroup difference in dFNC properties was found (all P > 0.05). DATA CONCLUSION: Our findings suggest aberrant dFNC properties in ALS, which is associated with disease severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Identification of Amyotrophic Lateral Sclerosis Based on Diffusion Tensor Imaging and Support Vector Machine.

Objectives: White matter (WM) impairments involving both motor and extra-motor areas have been well-documented in amyotrophic lateral sclerosis (ALS). This study tested the potential of diffusion measurements in WM for identifying ALS based on support vector machine (SVM). Methods: Voxel-wise fractional anisotropy (FA) values of diffusion tensor images (DTI) were extracted from 22 ALS patients and 26 healthy controls and served as discrimination features. The revised ALS Functional Rating Scale (ALSFRS-R) was employed to assess ALS severity. Feature ranking and selection were based on Fisher scores. A linear kernel SVM algorithm was applied to build the classification model, from which the classification performance was evaluated. To promote classifier generalization ability, a leave-one-out cross-validation (LOOCV) method was adopted. Results: By using the 2,400~3,400 ranked features as optimal features, the highest classification accuracy of 83.33% (sensitivity = 77.27% and specificity = 88.46%, P = 0.0001) was achieved, with an area under receiver operating characteristic curve of 0.862. The predicted function value was positively correlated with patient ALSFRS-R scores (r = 0.493, P = 0.020). In the optimized SVM model, FA values from several regions mostly contributed to classification, primarily involving the corticospinal tract pathway, postcentral gyrus, and frontal and parietal areas. Conclusions: Our results suggest the feasibility of ALS diagnosis based on SVM analysis and diffusion measurements of WM. Additional investigations using a larger cohort is recommended in order to validate the results of this study.

Brain Cortical Complexity Alteration in Amyotrophic Lateral Sclerosis: A Preliminary Fractal Dimensionality Study.

OBJECTIVE: Fractal dimensionality (FD) analysis provides a quantitative description of brain structural complexity. The application of FD analysis has provided evidence of amyotrophic lateral sclerosis- (ALS-) related white matter degeneration. This study is aimed at evaluating, for the first time, FD alterations in a gray matter in ALS and determining its association with clinical parameters. Materials and Methods. This study included 22 patients diagnosed with ALS and 20 healthy subjects who underwent high-resolution T1-weighted imaging scanning. Disease severity was assessed using the revised ALS Functional Rating Scale (ALSFRS-R). The duration of symptoms and rate of disease progression were also assessed. The regional FD value was calculated by a computational anatomy toolbox and compared among groups. The relationship between cortical FD values and clinical parameters was evaluated by Spearman correlation analysis. RESULTS: ALS patients showed decreased FD values in the left precentral gyrus and central sulcus, left circular sulcus of insula (superior segment), left cingulate gyrus and sulcus (middle-posterior part), right precentral gyrus, and right postcentral gyrus. The FD values in the right precentral gyrus were positively correlated to ALSFRS-R scores (r = 0.44 and P = 0.023), whereas negatively correlated to the rate of disease progression (r = 0.44 and P = 0.023), whereas negatively correlated to the rate of disease progression (r = 0.44 and P = 0.023), whereas negatively correlated to the rate of disease progression (. CONCLUSIONS: Our results suggest an ALS-related reduction in structural complexity involving the gray matter. FD analysis may shed more light on the pathophysiology of ALS.

Reduced Cortical Complexity in Cirrhotic Patients with Minimal Hepatic Encephalopathy.

Purpose: Gray matter volume loss, regional cortical thinning, and local gyrification index alteration have been documented in minimal hepatic encephalopathy (MHE). Fractal dimension (FD), another morphological parameter, has been widely used to describe structural complexity alterations in neurological or psychiatric disease. Here, we conducted the first study to investigate FD alterations in MHE. Methods and Materials: We performed high-resolution structural magnetic resonance imaging on cirrhotic patients with MHE (n = 20) and healthy controls (n = 21). We evaluated their cognitive performance using the psychometric hepatic encephalopathy score (PHES). The regional FD value was calculated by Computational Anatomy Toolbox (CAT12) and compared between groups. We further estimated the association between patients' cognitive performance and FD values. Results: MHE patients presented significantly decreased FD values in the left precuneus, left supramarginal gyrus, right caudal anterior cingulate cortex, right isthmus cingulate cortex, right insula, bilateral pericalcarine cortex, and bilateral paracentral cortex compared to normal controls. In addition, the FD values in the right isthmus cingulate cortex and right insula were shown to be positively correlated with patients' cognitive performance. Conclusion: Aberrant cortical complexity is an additional characteristic of MHE, and FD analysis may provide novel insight into the neurobiological basis of cognitive dysfunction in MHE.

Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which cerebral structural impairment is a consistent feature. PURPOSE: To investigate cerebral microstructural changes in ALS using diffusion kurtosis imaging (DKI) for the first time. STUDY TYPE: Prospective. SUBJECTS: Eighteen ALS patients and 20 healthy controls. FIELD STRENGTH/SEQUENCE: DKI images were obtained by a spin-echo echo-planar imaging sequence on a 3T MRI scanner, with three b-values (0, 1000, and 2000 s/mm2 ) and 64 diffusion encoding directions. ASSESSMENT: The revised ALS Functional Rating Scale (ALSFRS-R) was administered to assess disease severity, and the symptom duration and disease progression rate were also recorded. Voxel-based analysis was applied to examine the alteration of DKI metrics (ie, mean kurtosis metrics [MK], axial kurtosis [AK], and radial kurtosis [RK]) and the conventional diffusion metrics (ie, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). STATISTICAL TESTS: Student's t-test, chi-square test, and Pearson correlation analysis. RESULTS: ALS patients showed MK reductions in gray matter areas, including the bilateral precentral gyrus, bilateral paracentral lobule, and left anterior cingulate gyrus; they also showed decreased MK values in white matter (WM) in the bilateral precentral gyrus, bilateral corona radiata, bilateral middle corpus callosum, left occipital lobe, and right superior parietal lobule. The spatial distribution of the regions with reduced RK was similar to those with decreased MK. No significant AK difference was found between groups. The correlation analysis revealed significant associations between DKI metrics and clinical assessments such as ALSFRS-R score and disease duration. Additionally, several WM regions showed between-group differences in conventional diffusion metrics; but the spatial extent was smaller than that with reduced DKI metrics. DATA CONCLUSION: The reduction in DKI metrics indicates decreased microstructural complexity in ALS, involving both motor-related areas and extramotor regions. DKI metrics can serve as potential biomarkers for assessing disease severity. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:554-562.

Brain white matter abnormalities and correlation with severity in amyotrophic lateral sclerosis: An atlas-based diffusion tensor imaging study.

OBJECTIVES: To assess microstructural alterations in white matter (WM) in amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). METHODS: DTI data were collected from 34 subjects (18 patients with ALS and 16 healthy controls). The atlas-based region of interest (ROI) analysis was conducted to assess WM microstructure in ALS by combining intra-voxel metrics, which included fractional anisotropy (FA) and mean diffusivity (MD), and an inter-voxel metric, i.e., local diffusion homogeneity (LDH). Correlation analysis of diffusion values and clinical factors was also performed. RESULTS: ALS group showed a significant FA reduction in bilateral corticospinal tract (CST) as well as right uncinate fasciculus (RUF). The areas with higher MD were situated in right corticospinal tract (RCST), left cingulum hippocampus (LCH), RUF, and right superior longitudinal fasciculus (RSLF). Additionally, ALS patients showed decreased LDH in bilateral anterior thalamic radiation (ATR), bilateral CST and left inferior frontal-occipital fasciculus (LIFOF). Significant correlations were observed between ALSFRS-R (revised ALS Functional Rating Scale) scores or progression rate and FA in bilateral CST, as well as between disease duration and LDH in right CST. Receiver operating characteristic (ROC) analysis revealed the feasibility of employing diffusion metrics along the CST to distinguish two groups (AUC = 0.792-0.868, p < .005 for all). CONCLUSIONS: WM microstructural alteration is a common pathology in ALS, which can be detected by both intra- and inter-voxel diffusion metrics. The extent of abnormalities in several WM tracts such as ATR and LIFOF may be better assessed through the inter-voxel diffusion measurement.