Myelin Changes in Poor Sleepers: Insights into Glymphatic Clearance Function and Regional Circadian Clock Gene Expression.

Sleep is essential for maintaining brain myelin integrity. Emerging evidence suggests that poor sleep quality compromises the glymphatic system, a perivascular network crucial for brain waste clearance, leading to the accumulation of neuroinflammatory and toxic proteins, which may affect myelin integrity. Furthermore, poor sleep quality results in alterations in gene expression within the brain. We evaluated the associations among poor sleep quality, brain myelin integrity, and glymphatic clearance function as well as the impact of circadian clock gene expression on regional cortical myelin content. 50 poor sleepers (average age 71.08 ± 4.69 years; Pittsburgh Sleep Quality Index [PSQI] &;gt 5) and 50 good sleepers (average age 73.04 ± 5.80 years; PSQI ≤ 5) were assessed. Myelin volume fraction (MVF) was quantified using magnetization transfer saturation imaging, and glymphatic function was noninvasively examined using diffusion tensor imaging along the perivascular space. Circadian gene expression was analyzed using postmortem brain tissue from the Allen Human Brain Atlas. Magnetic resonance imaging measures were correlated with cognitive and depression scores. Lower MVF was observed in the fronto-temporo-parietal and limbic regions as well as in major white matter tracts in poor sleepers compared with that in good sleepers. This reduction was linked to lower cognitive function scores and higher depressive scores. Poor sleepers also exhibited lower diffusivity along the perivascular spaces, mediating the relationship between poor sleep quality and demyelination. Regions with higher expression of CLOCK, CRY2, PER1, and PER2 exhibited greater MVF disparities between good and poor sleepers, whereas lower expression of CRY1 was associated with more pronounced differences. Poor sleep quality was associated with lower brain myelin integrity, correlating with reduced cognitive performance and increased depressive symptoms. These changes might be mediated by glymphatic clearance dysfunction and were associated with the differential expression of circadian clock genes.

Deep Learning-based Hierarchical Brain Segmentation with Preliminary Analysis of the Repeatability and Reproducibility.

PURPOSE: We developed new deep learning-based hierarchical brain segmentation (DLHBS) method that can segment T1-weighted MR images (T1WI) into 107 brain subregions and calculate the volume of each subregion. This study aimed to evaluate the repeatability and reproducibility of volume estimation using DLHBS and compare them with those of representative brain segmentation tools such as statistical parametric mapping (SPM) and FreeSurfer (FS). METHODS: Hierarchical segmentation using multiple deep learning models was employed to segment brain subregions within a clinically feasible processing time. The T1WI and brain mask pairs in 486 subjects were used as training data for training of the deep learning segmentation models. Training data were generated using a multi-atlas registration-based method. The high quality of training data was confirmed through visual evaluation and manual correction by neuroradiologists. The brain 3D-T1WI scan-rescan data of the 11 healthy subjects were obtained using three MRI scanners for evaluating the repeatability and reproducibility. The volumes of the eight ROIs-including gray matter, white matter, cerebrospinal fluid, hippocampus, orbital gyrus, cerebellum posterior lobe, putamen, and thalamus-obtained using DLHBS, SPM 12 with default settings, and FS with the "recon-all" pipeline. These volumes were then used for evaluation of repeatability and reproducibility. RESULTS: In the volume measurements, the bilateral thalamus showed higher repeatability with DLHBS compared with SPM. Furthermore, DLHBS demonstrated higher repeatability than FS in across all eight ROIs. Additionally, higher reproducibility was observed with DLHBS in both hemispheres of six ROIs when compared with SPM and in five ROIs compared with FS. The lower repeatability and reproducibility in DLHBS were not observed in any comparisons. CONCLUSION: Our results showed that the best performance in both repeatability and reproducibility was found in DLHBS compared with SPM and FS.

Three-dimensional simultaneous T1 and T2* relaxation times and quantitative susceptibility mapping at 3 T: A multicenter validation study.

We aimed to determine the intra-site repeatability and cross-site reproducibility of T1 and T2* relaxation times and quantitative susceptibility (χ) values obtained through quantitative parameter mapping (QPM) at 3 T. This prospective study included three 3-T scanners with the same hardware and software platform at three sites. The brains of twelve healthy volunteers were scanned three times using QPM at three sites. Intra-site repeatability and cross-site reproducibility were evaluated based on voxel-wise and region-of-interest analyses. The within-subject coefficient of variation (wCV), within-subject standard deviation (wSD), linear regression, Bland-Altman plot, and intraclass correlation coefficient (ICC) were used for evaluation. The intra-site repeatability wCV was 11.9 ± 6.86% for T1 and 3.15 ± 0.03% for T2*, and wSD of χ at 3.35 ± 0.10 parts per billion (ppb). Intra-site ICC(1,k) values for T1, T2*, and χ were 0.878-0.904, 0.972-0.976, and 0.966-0.972, respectively, indicating high consistency within the same scanner. Linear regression analysis revealed a strong agreement between measurements from each site and the site-average measurement, with R-squared values ranging from 0.79 to 0.83 for T1, 0.94-0.95 for T2*, and 0.95-0.96 for χ. The cross-site wCV was 13.4 ± 5.47% for T1 and 3.69 ± 2.25% for T2*, and cross-site wSD of χ at 4.08 ± 3.22 ppb. The cross-site ICC(2,1) was 0.707, 0.913, and 0.902 for T1, T2*, and χ, respectively. QPM provides T1, T2*, and χ values with an intra-site repeatability of <12% and cross-site reproducibility of <14%. These findings may contribute to the development of multisite studies.

Assessing interstitial fluid dynamics in type 2 diabetes mellitus and prediabetes cases through diffusion tensor imaging analysis along the perivascular space.

Background and purpose: Glymphatic system in type 2 diabetes mellitus (T2DM) but not in the prodrome, prediabetes (Pre-DM) was investigated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Association between glymphatic system and insulin resistance of prominent characteristic in T2DM and Pre-DM between is yet elucidated. Therefore, this study delves into the interstitial fluid dynamics using the DTI-ALPS in both Pre-DM and T2DM and association with insulin resistance. Materials and methods: In our cross-sectional study, we assessed 70 elderly individuals from the Bunkyo Health Study, which included 22 with Pre-DM, 18 with T2DM, and 33 healthy controls with normal glucose metabolism (NGM). We utilized the general linear model (GLM) to evaluate the ALPS index based on DTI-ALPS across these groups, considering variables like sex, age, intracranial volume, years of education, anamnesis of hypertension and hyperlipidemia, and the total Fazekas scale. Furthermore, we have explored the relationship between the ALPS index and insulin resistance, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using GLM and the same set of covariates. Results: In the T2DM group, the ALPS index demonstrated a reduction compared with the NGM group [family-wise error (FWE)-corrected p < 0.001; Cohen's d = -1.32]. Similarly, the Pre-DM group had a lower ALPS index than the NGM group (FWE-corrected p < 0.001; Cohen's d = -1.04). However, there was no significant disparity between the T2DM and Pre-DM groups (FWE-corrected p = 1.00; Cohen's d = -0.63). A negative correlation was observed between the ALPS index and HOMA-IR in the combined T2DM and Pre-DM groups (partial correlation coefficient r = -0.35, p < 0.005). Conclusion: The ALPS index significantly decreased in both the pre-DM and T2DM groups and showed a correlated with insulin resistance. This indicated that changes in interstitial fluid dynamics are associated with insulin resistance.

Free-water diffusion magnetic resonance imaging under selegiline treatment in Parkinson's disease.

INTRODUCTION: Monoamine oxidase type B inhibitors, including selegiline, are established as anti-Parkinsonian Drugs. Inhibition of monoamine oxidase type B enzymes might suppress the inflammation because of inhibition to generate reactive oxygen species. However, its effect on brain microstructure remains unclear. The aim of this study is to elucidate white matter and substantia nigra (SN) microstructural differences between Patients with Parkinson's disease with and without selegiline treatment by two independently recruited cohorts. METHODS: Diffusion tensor imaging and free water imaging indices of WM and SN were compared among 22/15 Patients with Parkinson's disease with selegiline (PDselegiline(+)), 33/23 Patients with Parkinson's disease without selegiline (PDselegiline(-)), and 25/20 controls, in the first/second cohorts. Two cohorts were analyzed with different MRI protocols. RESULTS: Diffusion tensor imaging and free-water indices of major white matter tracts were significantly differed between the PDselegiline(-) and controls in both cohorts, although not between the PDselegiline(+) and controls except for restricted areas. Compared with the PDselegiline(+), free-water was significantly higher in the PDselegiline(-) in the inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and superior and posterior corona radiata (first cohort) and the forceps major and splenium of the corpus callosum (second cohort). There were no significant differences in free-water of anterior or posterior substantia nigra between PDselegiline(+) and PDselegiline(-). CONCLUSIONS: Selegiline treatment might reduce the white matter microstructural abnormalities detected by free-water imaging in Parkinson's disease.

Cross-vendor multiparametric mapping of the human brain using 3D-QALAS: A multicenter and multivendor study.

PURPOSE: To evaluate a vendor-agnostic multiparametric mapping scheme based on 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) for whole-brain T1, T2, and proton density (PD) mapping. METHODS: This prospective, multi-institutional study was conducted between September 2021 and February 2022 using five different 3T systems from four prominent MRI vendors. The accuracy of this technique was evaluated using a standardized MRI system phantom. Intra-scanner repeatability and inter-vendor reproducibility of T1, T2, and PD values were evaluated in 10 healthy volunteers (6 men; mean age ± SD, 28.0 ± 5.6 y) who underwent scan-rescan sessions on each scanner (total scans = 100). To evaluate the feasibility of 3D-QALAS, nine patients with multiple sclerosis (nine women; mean age ± SD, 48.2 ± 11.5 y) underwent imaging examination on two 3T MRI systems from different manufacturers. RESULTS: Quantitative maps obtained with 3D-QALAS showed high linearity (R2 = 0.998 and 0.998 for T1 and T2, respectively) with respect to reference measurements. The mean intra-scanner coefficients of variation for each scanner and structure ranged from 0.4% to 2.6%. The mean structure-wise test-retest repeatabilities were 1.6%, 1.1%, and 0.7% for T1, T2, and PD, respectively. Overall, high inter-vendor reproducibility was observed for all parameter maps and all structure measurements, including white matter lesions in patients with multiple sclerosis. CONCLUSION: The vendor-agnostic multiparametric mapping technique 3D-QALAS provided reproducible measurements of T1, T2, and PD for human tissues within a typical physiological range using 3T scanners from four different MRI manufacturers.

Surface-based Analyses of Diffusional Kurtosis Imaging in Amyotrophic Lateral Sclerosis: Relationship with Onset Subtypes.

PURPOSE: Here, we aimed to characterize the cortical and subcortical microstructural alterations in the brains of patients with amyotrophic lateral sclerosis (ALS). In particular, we compared these features between bulbar-onset ALS (b-ALS) and limb-onset ALS (l-ALS). METHODS: Diffusion MRI data (b = 0, 700, 2000 ms/mm2, 1.7-mm isotropic voxel) from 28 patients with ALS (9 b-ALS and 19 l-ALS) and 17 healthy control subjects (HCs) were analyzed. Diffusional kurtosis imaging (DKI) metrics were sampled at the mid-cortical and subcortical surfaces. We used permutation testing with a nonparametric combination of mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) to assess intergroup differences over the cerebrum. We also carried out an atlas-based analysis focusing on Brodmann Area 4 and 6 (primary motor and premotor areas) and investigated the correlation between MRI metrics and clinical parameters. RESULTS: At both the mid-cortical and subcortical surfaces, b-ALS was associated with significantly greater MD, smaller FA, and smaller MK in the motor and premotor areas than HC. In contrast, the patients with l-ALS showed relatively moderate differences relative to HCs. The ALS Functional Rating Scale-Revised bulbar subscore was significantly correlated with the diffusion metrics in Brodmann Area 4. CONCLUSION: The distribution of abnormalities over the cerebral hemispheres and the more severe microstructural alteration in b-ALS compared to l-ALS were in good agreement with findings from postmortem histology. Our results suggest the feasibility of surface-based DKI analyses for exploring brain microstructural pathologies in ALS. The observed differences between b-ALS and l-ALS and their correlations with functional bulbar impairment support the clinical relevance of DKI measurement in the cortical and juxtacortical regions of patients with ALS.

Noninvasive Magnetic Resonance Imaging Measures of Glymphatic System Activity.

The comprehension of the glymphatic system, a postulated mechanism responsible for the removal of interstitial solutes within the central nervous system (CNS), has witnessed substantial progress recently. While direct measurement techniques involving fluorescence and contrast agent tracers have demonstrated success in animal studies, their application in humans is invasive and presents challenges. Hence, exploring alternative noninvasive approaches that enable glymphatic research in humans is imperative. This review primarily focuses on several noninvasive magnetic resonance imaging (MRI) techniques, encompassing perivascular space (PVS) imaging, diffusion tensor image analysis along the PVS, arterial spin labeling, chemical exchange saturation transfer, and intravoxel incoherent motion. These methodologies provide valuable insights into the dynamics of interstitial fluid, water permeability across the blood-brain barrier, and cerebrospinal fluid flow within the cerebral parenchyma. Furthermore, the review elucidates the underlying concept and clinical applications of these noninvasive MRI techniques, highlighting their strengths and limitations. It addresses concerns about the relationship between glymphatic system activity and pathological alterations, emphasizing the necessity for further studies to establish correlations between noninvasive MRI measurements and pathological findings. Additionally, the challenges associated with conducting multisite studies, such as variability in MRI systems and acquisition parameters, are addressed, with a suggestion for the use of harmonization methods, such as the combined association test (COMBAT), to enhance standardization and statistical power. Current research gaps and future directions in noninvasive MRI techniques for assessing the glymphatic system are discussed, emphasizing the need for larger sample sizes, harmonization studies, and combined approaches. In conclusion, this review provides invaluable insights into the application of noninvasive MRI methods for monitoring glymphatic system activity in the CNS. It highlights their potential in advancing our understanding of the glymphatic system, facilitating clinical applications, and paving the way for future research endeavors in this field. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Advancements in Diffusion MRI Tractography for Neurosurgery.

ABSTRACT: Diffusion magnetic resonance imaging tractography is a noninvasive technique that enables the visualization and quantification of white matter tracts within the brain. It is extensively used in preoperative planning for brain tumors, epilepsy, and functional neurosurgical procedures such as deep brain stimulation. Over the past 25 years, significant advancements have been made in imaging acquisition, fiber direction estimation, and tracking methods, resulting in considerable improvements in tractography accuracy. The technique enables the mapping of functionally critical pathways around surgical sites to avoid permanent functional disability. When the limitations are adequately acknowledged and considered, tractography can serve as a valuable tool to safeguard critical white matter tracts and provides insight regarding changes in normal white matter and structural connectivity of the whole brain beyond local lesions. In functional neurosurgical procedures such as deep brain stimulation, it plays a significant role in optimizing stimulation sites and parameters to maximize therapeutic efficacy and can be used as a direct target for therapy. These insights can aid in patient risk stratification and prognosis. This article aims to discuss state-of-the-art tractography methodologies and their applications in preoperative planning and highlight the challenges and new prospects for the use of tractography in daily clinical practice.

MR Fingerprinting for Contrast Agent-free and Quantitative Characterization of Focal Liver Lesions.

Purpose To evaluate the feasibility of liver MR fingerprinting (MRF) for quantitative characterization and diagnosis of focal liver lesions. Materials and Methods This single-site, prospective study included 89 participants (mean age, 62 years ± 15 [SD]; 45 women, 44 men) with various focal liver lesions who underwent MRI between October 2021 and August 2022. The participants underwent routine clinical MRI, non-contrast-enhanced liver MRF, and reference quantitative MRI with a 1.5-T MRI scanner. The bias and repeatability of the MRF measurements were assessed using linear regression, Bland-Altman plots, and coefficients of variation. The diagnostic capability of MRF-derived T1, T2, T2*, proton density fat fraction (PDFF), and a combination of these metrics to distinguish benign from malignant lesions was analyzed according to the area under the receiver operating characteristic curve (AUC). Results Liver MRF measurements showed moderate to high agreement with reference measurements (intraclass correlation = 0.94, 0.77, 0.45, and 0.61 for T1, T2, T2*, and PDFF, respectively), with underestimation of T2 values (mean bias in lesion = -0.5%, -29%, 5.8%, and -8.2% for T1, T2, T2*, and PDFF, respectively). The median coefficients of variation for repeatability of T1, T2, and T2* values were 2.5% (IQR, 3.6%), 3.1% (IQR, 5.6%), and 6.6% (IQR, 13.9%), respectively. After considering multicollinearity, a combination of MRF measurements showed a high diagnostic performance in differentiating benign from malignant lesions (AUC = 0.92 [95% CI: 0.86, 0.98]). Conclusion Liver MRF enabled the quantitative characterization of various focal liver lesions in a single breath-hold acquisition. Keywords: MR Imaging, Abdomen/GI, Liver, Imaging Sequences, Technical Aspects, Tissue Characterization, Technology Assessment, Diagnosis, Liver Lesions, MR Fingerprinting, Quantitative Characterization Supplemental material is available for this article. © RSNA, 2023.

Traveling Subject-Informed Harmonization Increases Reliability of Brain Diffusion Tensor and Neurite Mapping.

Diffusion-weighted magnetic resonance imaging (dMRI) of brain has helped elucidate the microstructural changes of psychiatric and neurodegenerative disorders. Inconsistency between MRI models has hampered clinical application of dMRI-based metrics. Using harmonized dMRI data of 300 scans from 69 traveling subjects (TS) scanning the same individuals at multiple conditions with 13 MRI models and 2 protocols, the widely-used metrics such as diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) were evaluated before and after harmonization with a combined association test (ComBat) or TS-based general linear model (TS-GLM). Results showed that both ComBat and TS-GLM significantly reduced the effects of the MRI site, model, and protocol for diffusion metrics while maintaining the intersubject biological effects. The harmonization power of TS-GLM based on TS data model is more powerful than that of ComBat. In conclusion, our research demonstrated that although ComBat and TS-GLM harmonization approaches were effective at reducing the scanner effects of the site, model, and protocol for DTI and NODDI metrics in WM, they exhibited high retainability of biological effects. Therefore, we suggest that, after harmonizing DTI and NODDI metrics, a multisite study with large cohorts can accurately detect small pathological changes by retaining pathological effects.

Functional connectivity in autism spectrum disorder evaluated using rs-fMRI and DKI.

We evaluated functional connectivity (FC) in patients with adult autism spectrum disorder (ASD) using resting-state functional MRI (rs-fMRI) and diffusion kurtosis imaging (DKI). We acquired rs-fMRI data from 33 individuals with ASD and 33 healthy controls (HC) and DKI data from 18 individuals with ASD and 17 HC. ASD showed attenuated FC between the right frontal pole (FP) and the bilateral temporal fusiform cortex (TFusC) and enhanced FC between the right thalamus and the bilateral inferior division of lateral occipital cortex, and between the cerebellar vermis and the right occipital fusiform gyrus (OFusG) and the right lingual gyrus, compared with HC. ASD demonstrated increased axial kurtosis (AK) and mean kurtosis (MK) in white matter (WM) tracts, including the right anterior corona radiata (ACR), forceps minor (FM), and right superior longitudinal fasciculus (SLF). In ASD, there was also a significant negative correlation between MK and FC between the cerebellar vermis and the right OFusG in the corpus callosum, FM, right SLF and right ACR. Increased DKI metrics might represent neuroinflammation, increased complexity, or disrupted WM tissue integrity that alters long-distance connectivity. Nonetheless, protective or compensating adaptations of inflammation might lead to more abundant glial cells and cytokine activation effectively alleviating the degeneration of neurons, resulting in increased complexity. FC abnormality in ASD observed in rs-fMRI may be attributed to microstructural alterations of the commissural and long-range association tracts in WM as indicated by DKI.

Fiber-specific micro- and macroscopic white matter alterations in progressive supranuclear palsy and corticobasal syndrome.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are characterized by progressive white matter (WM) alterations associated with the prion-like spreading of four-repeat tau, which has been pathologically confirmed. It has been challenging to monitor the WM degeneration patterns underlying the clinical deficits in vivo. Here, a fiber-specific fiber density and fiber cross-section, and their combined measure estimated using fixel-based analysis (FBA), were cross-sectionally and longitudinally assessed in PSP (n = 20), CBS (n = 17), and healthy controls (n = 20). FBA indicated disease-specific progression patterns of fiber density loss and subsequent bundle atrophy consistent with the tau propagation patterns previously suggested in a histopathological study. This consistency suggests the new insight that FBA can monitor the progressive tau-related WM changes in vivo. Furthermore, fixel-wise metrics indicated strong correlations with motor and cognitive dysfunction and the classifiability of highly overlapping diseases. Our findings might also provide a tool to monitor clinical decline and classify both diseases.

Percutaneous transjugular approach without arterial monitoring for the treatment of a direct carotid-cavernous fistula with vascular Ehlers-Danlos syndrome: illustrative case.

BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) because of COL3A1 mutations is a rare inherited collagen vascular disease associated with spontaneous arterial dissections, aneurysms, vessel rupture, and organ rupture. A direct carotid-cavernous fistula (CCF) is the most common central nervous system vascular anomaly in vEDS; however, its treatment is challenging due to extremely fragile arteries and veins. OBSERVATIONS: A 22-year-old woman presented with pulsatile tinnitus and mild diplopia. CCF formation without trauma, cervical dissecting aneurysms, thin skin, and multiple ligament tears, as well as a genetic analysis, led to a diagnosis of vEDS. To minimize the risk of vascular injury in the thoracoperitoneal cavity, the internal jugular vein was directly punctured and the CCF was embolized transvenously using the triple-overlay road-mapping technique without arterial monitoring. The CCF was completely occluded, and the patient showed an excellent clinical course without neurological or vascular complications. LESSONS: Physicians and neurosurgeons should consider vEDS when treating younger patients with spontaneous CCF without trauma and investigate the possibility of genetic abnormalities and systemic vascular pathology. Transvenous embolization of a CCF through the transjugular route using the triple-overlay road-mapping technique can minimize the risk of vascular injury in a patient with vEDS.

Fiber-Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations.

BACKGROUND: Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA-PD) have a more aggressive disease course than those with idiopathic PD (iPD). OBJECTIVE: The objective of this study was to investigate fiber-specific white matter (WM) differences in nonmedicated patients with early-stage GBA-PD and iPD using fixel-based analysis, a novel technique to assess tract-specific WM microstructural and macrostructural features comprehensively. METHODS: Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA-PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses. RESULTS: Patients with GBA-PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal-thalamo-cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal-thalamo-cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA-PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α-synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores. CONCLUSIONS: We report reduced fiber-specific WM density and bundle cross-sectional size in patients with GBA-PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α-synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Reduced neurite density index in the prefrontal cortex of adults with autism assessed using neurite orientation dispersion and density imaging.

Background: Core symptoms of autism-spectrum disorder (ASD) have been associated with prefrontal cortex abnormalities. However, the mechanisms behind the observation remain incomplete, partially due to the challenges of modeling complex gray matter (GM) structures. This study aimed to identify GM microstructural alterations in adults with ASD using neurite orientation dispersion and density imaging (NODDI) and voxel-wise GM-based spatial statistics (GBSS) to reduce the partial volume effects from the white matter and cerebrospinal fluid. Materials and methods: A total of 48 right-handed participants were included, of which 22 had ASD (17 men; mean age, 34.42 ± 8.27 years) and 26 were typically developing (TD) individuals (14 men; mean age, 32.57 ± 9.62 years). The metrics of NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) were compared between groups using GBSS. Diffusion tensor imaging (DTI) metrics and surface-based cortical thickness were also compared. The associations between magnetic resonance imaging-based measures and ASD-related scores, including ASD-spectrum quotient, empathizing quotient, and systemizing quotient were also assessed in the region of interest (ROI) analysis. Results: After controlling for age, sex, and intracranial volume, GBSS demonstrated significantly lower NDI in the ASD group than in the TD group in the left prefrontal cortex (caudal middle frontal, lateral orbitofrontal, pars orbitalis, pars triangularis, rostral middle frontal, and superior frontal region). In the ROI analysis of individuals with ASD, a significantly positive correlation was observed between the NDI in the left rostral middle frontal, superior frontal, and left frontal pole and empathizing quotient score. No significant between-group differences were observed in all DTI metrics, other NODDI (i.e., ODI and ISOVF) metrics, and cortical thickness. Conclusion: GBSS analysis was used to demonstrate the ability of NODDI metrics to detect GM microstructural alterations in adults with ASD, while no changes were detected using DTI and cortical thickness evaluation. Specifically, we observed a reduced neurite density index in the left prefrontal cortices associated with reduced empathic abilities.

Glymphatic system impairment in sleep disruption: diffusion tensor image analysis along the perivascular space (DTI-ALPS).

PURPOSE: This study aimed to evaluate the relationship between sleep quality as assessed using the Pittsburgh Sleep Quality Index (PSQI) and the index of diffusivity along the perivascular space (ALPS index), a possible indirect indicator of glymphatic system activity. MATERIALS AND METHODS: This study included the diffusion magnetic resonance imaging (MRI) data of 317 people with sleep disruption and 515 healthy controls (HCs) from the Human Connectome Project (WU-MINN HCP 1200). The ALPS index was calculated automatically based on diffusion tensor image analysis (DTI)-ALPS of diffusion MRI. The ALPS index of the sleep disruption and HC groups was compared using general linear model (GLM) analysis with covariates, such as age, sex, level of education, and intracranial volume. In addition, to confirm the relationship between sleep quality and the ALPS index in the sleep disruption group as well as evaluate the effect of each PSQI component on the ALPS index, correlation analyses between the ALPS indices and PSQI scores of all the components and between the ALPS index and each PSQI component was performed using GLM analysis with the abovementioned covariates, respectively. RESULTS: The ALPS index was significantly lower in the sleep disruption group than in the HC group (p = 0.001). Moreover, the ALPS indices showed significant negative correlations with the PSQI scores of all the components (false discovery rate [FDR]-corrected p < 0.001). Two significant negative correlations were also found between the ALPS index and PSQI component 2 (sleep latency, FDR-corrected p < 0.001) and 6 (the use of sleep medication, FDR-corrected p < 0.001). CONCLUSION: Our findings suggest that glymphatic system impairment contributes to sleep disruption in young adults.

Glymphatic system impairment in corticobasal syndrome: diffusion tensor image analysis along the perivascular space (DTI-ALPS).

PURPOSE: This study aimed to evaluate the along the perivascular space (ALPS) index based on the diffusion tensor image ALPS (DTI-ALPS) in corticobasal degeneration with corticobasal syndrome (CBD-CBS) and investigate its correlation with motor and cognitive functions. MATERIALS AND METHODS: The data of 21 patients with CBD-CBS and 17 healthy controls (HCs) were obtained from the 4-Repeat Tauopathy Neuroimaging Initiative and the Frontotemporal Lobar Degeneration Neuroimaging Initiative databases. Diffusion magnetic resonance imaging was performed using a 3-Tesla MRI scanner. The ALPS index based on DTI-ALPS was automatically calculated after preprocessing. The ALPS index was compared between the CBD-CBS and HC groups via a general linear model analysis, with covariates such as age, sex, years of education, and intracranial volume (ICV). Furthermore, to confirm the relation between the ALPS index and the motor and cognitive score in CBD-CBS, the partial Spearman's rank correlation coefficient was calculated with covariates such as age, sex, years of education, and ICV. A p value of < 0.05 was considered as statistically significant in all statistical analyses. RESULTS: The ALPS index of CBD-CBS was significantly lower than that of HC (Cohen's d = - 1.53, p < 0.005). Moreover, the ALPS index had a significant positive correlation with the mini mental state evaluation score (rs = 0.65, p < 0.005) and a significant negative correlation with the unified Parkinson's Disease Rating Scale III score (rs = - 0.75, p < 0.001). CONCLUSION: The ALPS index of patients with CBD-CBS, which is significantly lower than that of HCs, is significantly associated with motor and cognitive functions.