Normative volumes and relaxation times at 3T during brain development.

While research has unveiled and quantified brain markers of abnormal neurodevelopment, clinicians still work with qualitative metrics for MRI brain investigation. The purpose of the current article is to bridge the knowledge gap between case-control cohort studies and individual patient care. Here, we provide a unique dataset of seventy-three 3-to-17 years-old healthy subjects acquired with a 6-minute MRI protocol encompassing T1 and T2 relaxation quantitative sequence that can be readily implemented in the clinical setting; MP2RAGE for T1 mapping and the prototype sequence GRAPPATINI for T2 mapping. White matter and grey matter volumes were automatically quantified. We further provide normative developmental curves based on these two imaging sequences; T1, T2 and volume normative ranges with respect to age were computed, for each ROI of a pediatric brain atlas. This open-source dataset provides normative values allowing to position individual patients acquired with the same protocol on the brain maturation curve and as such provides potentially useful quantitative biomarkers facilitating precise and personalized care.

Associations of plasma neurofilament light chain with cognition and neuroimaging measures in community-dwelling early old age men.

BACKGROUND: Plasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations. METHODS: We examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61-73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter. RESULTS: After adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals. CONCLUSIONS: These results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia.

BACKGROUND: White matter injury (WMI) is an important pathological process after traumatic brain injury (TBI). The correlation between white matter functions and the myeloid cells expressing triggering receptor-2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism is crucial for early remyelination after demyelinating diseases. However, the potential roles of TREM2 expression and microglial sterol metabolism in WMI after TBI have not yet been explored. METHODS: Controlled cortical injury was induced in both wild-type (WT) and TREM2 depletion (TREM2 KO) mice to simulate clinical TBI. COG1410 was used to upregulate TREM2, while PLX5622 and GSK2033 were used to deplete microglia and inhibit the liver X receptor (LXR), respectively. Immunofluorescence, Luxol fast blue staining, magnetic resonance imaging, transmission electron microscopy, and oil red O staining were employed to assess WMI after TBI. Neurological behaviour tests and electrophysiological recordings were utilized to evaluate cognitive functions following TBI. Microglial cell sorting and transcriptomic sequencing were utilized to identify alterations in microglial sterol metabolism-related genes, while western blot was conducted to validate the findings. RESULTS: TREM2 expressed highest at 3 days post-TBI and was predominantly localized to microglial cells within the white matter. Depletion of TREM2 worsened aberrant neurological behaviours, and this phenomenon was mediated by the exacerbation of WMI, reduced renewal of oligodendrocytes, and impaired phagocytosis ability of microglia after TBI. Subsequently, the upregulation of TREM2 alleviated WMI, promoted oligodendrocyte regeneration, and ultimately facilitated the recovery of neurological behaviours after TBI. Finally, the expression of DHCR24 increased in TREM2 KO mice after TBI. Interestingly, TREM2 inhibited DHCR24 and upregulated members of the LXR pathway. Moreover, LXR inhibition could partially reverse the effects of TREM2 upregulation on electrophysiological activities. CONCLUSIONS: We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia.

Test-Retest Reproducibility of Reduced-Field-of-View Density-Weighted CRT MRSI at 3T.

Quantifying an imaging modality's ability to reproduce results is important for establishing its utility. In magnetic resonance spectroscopic imaging (MRSI), new acquisition protocols are regularly introduced which improve upon their precursors with respect to signal-to-noise ratio (SNR), total acquisition duration, and nominal voxel resolution. This study has quantified the within-subject and between-subject reproducibility of one such new protocol (reduced-field-of-view density-weighted concentric ring trajectory (rFOV-DW-CRT) MRSI) by calculating the coefficient of variance of data acquired from a test-retest experiment. The posterior cingulate cortex (PCC) and the right superior corona radiata (SCR) were selected as the regions of interest (ROIs) for grey matter (GM) and white matter (WM), respectively. CVs for between-subject and within-subject were consistently around or below 15% for Glx, tCho, and Myo-Ins, and below 5% for tNAA and tCr.

Improved inter-subject alignment of the lumbosacral cord for group-level in vivo gray and white matter assessments: A scan-rescan MRI study at 3T.

INTRODUCTION: Magnetic resonance imaging (MRI) enables the investigation of pathological changes in gray and white matter at the lumbosacral enlargement (LSE) and conus medullaris (CM). However, conducting group-level analyses of MRI metrics in the lumbosacral spinal cord is challenging due to variability in CM length, lack of established image-based landmarks, and unknown scan-rescan reliability. This study aimed to improve inter-subject alignment of the lumbosacral cord to facilitate group-level analyses of MRI metrics. Additionally, we evaluated the scan-rescan reliability of MRI-based cross-sectional area (CSA) measurements and diffusion tensor imaging (DTI) metrics. METHODS: Fifteen participants (10 healthy volunteers and 5 patients with spinal cord injury) underwent axial T2*-weighted and diffusion MRI at 3T. We assessed the reliability of spinal cord and gray matter-based landmarks for inter-subject alignment of the lumbosacral cord, the inter-subject variability of MRI metrics before and after adjusting for the CM length, the intra- and inter-rater reliability of CSA measurements, and the scan-rescan reliability of CSA measurements and DTI metrics. RESULTS: The slice with the largest gray matter CSA as an LSE landmark exhibited the highest reliability, both within and across raters. Adjusting for the CM length greatly reduced the inter-subject variability of MRI metrics. The intra-rater, inter-rater, and scan-rescan reliability of MRI metrics were the highest at and around the LSE (scan-rescan coefficient of variation <3% for CSA measurements and <7% for DTI metrics within the white matter) and decreased considerably caudal to it. CONCLUSIONS: To facilitate group-level analyses, we recommend using the slice with the largest gray matter CSA as a reliable LSE landmark, along with an adjustment for the CM length. We also stress the significance of the anatomical location within the lumbosacral cord in relation to the reliability of MRI metrics. The scan-rescan reliability values serve as valuable guides for power and sample size calculations in future longitudinal studies.

Hope for vascular cognitive impairment: Ac-YVAD-cmk as a novel treatment against white matter rarefaction.

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear. To address this, we performed BCAS on C57/BL6 mice to study the effects of Ac-YVAD-cmk, a caspase-1 inhibitor, on the subcortical and cortical regions. Cerebral blood flow (CBF), WMR, neuroinflammation and the expression of tight junction-related proteins associated with blood-brain barrier integrity were assessed 15 days post BCAS. We observed that Ac-YVAD-cmk restored CBF, attenuated BCAS-induced WMR and restored subcortical myelin expression. Within the subcortical region, BCAS activated the NLRP3/caspase-1/interleukin-1beta axis only within the subcortical region, which was attenuated by Ac-YVAD-cmk. Although we observed that BCAS induced significant increases in VCAM-1 expression in both brain regions that were attenuated with Ac-YVAD-cmk, only ZO-1 and occludin were observed to be significantly altered in the subcortical region. Here we show that caspase-1 may contribute to subcortical regional susceptibility in a mouse model of VCI. In addition, our results support further investigations into the potential of Ac-YVAD-cmk as a novel treatment strategy against subcortical VCI and other conditions exhibiting cerebral hypoperfusion-induced WMR.

Sex, gender diversity, and brain structure in early adolescence.

There remains little consensus about the relationship between sex and brain structure, particularly in early adolescence. Moreover, few pediatric neuroimaging studies have analyzed both sex and gender as variables of interest-many of which included small sample sizes and relied on binary definitions of gender. The current study examined gender diversity with a continuous felt-gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9-11 years old (N = 7195). Then, a statistical model-building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology, including subcortical volume, cortical thickness, gyrification, and white matter microstructure. Additional sensitivity analyses found that male versus female differences in gyrification and white matter were largely accounted for by total brain volume, rather than sex per se. The model with sex, but not gender diversity, was the best-fitting model in 60.1% of gray matter regions and 61.9% of white matter regions after adjusting for brain volume. The proportion of variance accounted for by sex was negligible to small in all cases. While models including felt-gender explained a greater amount of variance in a few regions, the felt-gender score alone was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9-11 years old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity.

White matter hyperintensity patterns: associations with comorbidities, amyloid, and cognition.

BACKGROUND: White matter hyperintensities (WMHs) are often measured globally, but spatial patterns of WMHs could underlie different risk factors and neuropathological and clinical correlates. We investigated the spatial heterogeneity of WMHs and their association with comorbidities, Alzheimer's disease (AD) risk factors, and cognition. METHODS: In this cross-sectional study, we studied 171 cognitively unimpaired (CU; median age: 65 years, range: 50 to 89) and 51 mildly cognitively impaired (MCI; median age: 72, range: 53 to 89) individuals with available amyloid (18F-flutementamol) PET and FLAIR-weighted images. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each participant's white matter was segmented into 38 parcels, and WMH volume was calculated in each parcel. Correlated principal component analysis was applied to the parceled WMH data to determine patterns of WMH covariation. Adjusted and unadjusted linear regression models were used to investigate associations of component scores with comorbidities and AD-related factors. Using multiple linear regression, we tested whether WMH component scores predicted cognitive performance. RESULTS: Principal component analysis identified four WMH components that broadly describe FLAIR signal hyperintensities in posterior, periventricular, and deep white matter regions, as well as basal ganglia and thalamic structures. In CU individuals, hypertension was associated with all patterns except the periventricular component. MCI individuals showed more diverse associations. The posterior and deep components were associated with renal disorders, the periventricular component was associated with increased amyloid, and the subcortical gray matter structures was associated with sleep disorders, endocrine/metabolic disorders, and increased amyloid. In the combined sample (CU + MCI), the main effects of WMH components were not associated with cognition but predicted poorer episodic memory performance in the presence of increased amyloid. No interaction between hypertension and the number of comorbidities on component scores was observed. CONCLUSION: Our study underscores the significance of understanding the regional distribution patterns of WMHs and the valuable insights that risk factors can offer regarding their underlying causes. Moreover, patterns of hyperintensities in periventricular regions and deep gray matter structures may have more pronounced cognitive implications, especially when amyloid pathology is also present.

Single-Cell Multi-Omics Map of Cell Type-Specific Mechanistic Drivers of Multiple Sclerosis Lesions.

BACKGROUND AND OBJECTIVES: In progressive multiple sclerosis (MS), compartmentalized inflammation plays a pivotal role in the complex pathology of tissue damage. The interplay between epigenetic regulation, transcriptional modifications, and location-specific alterations within white matter (WM) lesions at the single-cell level remains underexplored. METHODS: We examined intracellular and intercellular pathways in the MS brain WM using a novel dataset obtained by integrated single-cell multi-omics techniques from 3 active lesions, 3 chronic active lesions, 3 remyelinating lesions, and 3 control WM of 6 patients with progressive MS and 3 non-neurologic controls. Single-nucleus RNA-seq and ATAC-seq were combined and additionally enriched with newly conducted spatial transcriptomics from 1 chronic active lesion. Functional gene modules were then validated in our previously published bulk tissue transcriptome data obtained from 73 WM lesions of patients with progressive MS and 25 WM of non-neurologic disease controls. RESULTS: Our analysis uncovered an MS-specific oligodendrocyte genetic signature influenced by the KLF/SP gene family. This modulation has potential associations with the autocrine iron uptake signaling observed in transcripts of transferrin and its receptor LRP2. In addition, an inflammatory profile emerged within these oligodendrocytes. We observed unique cellular endophenotypes both at the periphery and within the chronic active lesion. These include a distinct metabolic astrocyte phenotype, the importance of FGF signaling among astrocytes and neurons, and a notable enrichment of mitochondrial genes at the lesion edge populated predominantly by astrocytes. Our study also identified B-cell coexpression networks indicating different functional B-cell subsets with differential location and specific tendencies toward certain lesion types. DISCUSSION: The use of single-cell multi-omics has offered a detailed perspective into the cellular dynamics and interactions in MS. These nuanced findings might pave the way for deeper insights into lesion pathogenesis in progressive MS.

The characteristic patterns of individual brain susceptibility networks underlie Alzheimer's disease and white matter hyperintensity-related cognitive impairment.

Excessive iron accumulation in the brain cortex increases the risk of cognitive deterioration. However, interregional relationships (defined as susceptibility connectivity) of local brain iron have not been explored, which could provide new insights into the underlying mechanisms of cognitive decline. Seventy-six healthy controls (HC), 58 participants with mild cognitive impairment due to probable Alzheimer's disease (MCI-AD) and 66 participants with white matter hyperintensity (WMH) were included. We proposed a novel approach to construct a brain susceptibility network by using Kullback‒Leibler divergence similarity estimation from quantitative susceptibility mapping and further evaluated its topological organization. Moreover, sparse logistic regression (SLR) was applied to classify MCI-AD from HC and WMH with normal cognition (WMH-NC) from WMH with MCI (WMH-MCI).The altered susceptibility connectivity in the MCI-AD patients indicated that relatively more connectivity was involved in the default mode network (DMN)-related and visual network (VN)-related connectivity, while more altered DMN-related and subcortical network (SN)-related connectivity was found in the WMH-MCI patients. For the HC vs. MCI-AD classification, the features selected by the SLR were primarily distributed throughout the DMN-related and VN-related connectivity (accuracy = 76.12%). For the WMH-NC vs. WMH-MCI classification, the features with high appearance frequency were involved in SN-related and DMN-related connectivity (accuracy = 84.85%). The shared and specific patterns of the susceptibility network identified in both MCI-AD and WMH-MCI may provide a potential diagnostic biomarker for cognitive impairment, which could enhance the understanding of the relationships between brain iron burden and cognitive decline from a network perspective.

[Repair effect of different doses of human umbilical cord mesenchymal stem cells on white matter injury in neonatal rats]. / 不同剂量人脐带间å è´¨å¹²ç»†èƒžç§»æ¤å¯¹æ–°ç”Ÿå¤§é¼ è„‘ç™½è´¨æŸä¼¤çš„ä¿®å¤ä½œç”¨.

OBJECTIVES: To compare the repair effects of different doses of human umbilical cord mesenchymal stem cells (hUC-MSCs) on white matter injury (WMI) in neonatal rats. METHODS: Two-day-old Sprague-Dawley neonatal rats were randomly divided into five groups: sham operation group, WMI group, and hUC-MSCs groups (low dose, medium dose, and high dose), with 24 rats in each group. Twenty-four hours after successful establishment of the neonatal rat white matter injury model, the WMI group was injected with sterile PBS via the lateral ventricle, while the hUC-MSCs groups received injections of hUC-MSCs at different doses. At 14 and 21 days post-modeling, hematoxylin and eosin staining was used to observe pathological changes in the tissues around the lateral ventricles. Real-time quantitative polymerase chain reaction was used to detect the quantitative expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) mRNA in the brain tissue. Immunohistochemistry was employed to observe the expression levels of GFAP and neuron-specific nuclear protein (NeuN) in the tissues around the lateral ventricles. TUNEL staining was used to observe cell apoptosis in the tissues around the lateral ventricles. At 21 days post-modeling, the Morris water maze test was used to observe the spatial learning and memory capabilities of the neonatal rats. RESULTS: At 14 and 21 days post-modeling, numerous cells with nuclear shrinkage and rupture, as well as disordered arrangement of nerve fibers, were observed in the tissues around the lateral ventricles of the WMI group and the low dose group. Compared with the WMI group, the medium and high dose groups showed alleviated pathological changes; the arrangement of nerve fibers in the medium dose group was relatively more orderly compared with the high dose group. Compared with the WMI group, there was no significant difference in the expression levels of MBP and GFAP mRNA in the low dose group (P>0.05), while the expression levels of MBP mRNA increased and GFAP mRNA decreased in the medium and high dose groups. The expression level of MBP mRNA in the medium dose group was higher than that in the high dose group, and the expression level of GFAP mRNA in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the protein expression of GFAP and NeuN in the low dose group (P>0.05), while the expression of NeuN protein increased and GFAP protein decreased in the medium and high dose groups. The expression of NeuN protein in the medium dose group was higher than that in the high dose group, and the expression of GFAP protein in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the number of apoptotic cells in the low dose group (P>0.05), while the number of apoptotic cells in the medium and high dose groups was less than that in the WMI group, and the number of apoptotic cells in the medium dose group was less than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the escape latency time in the low dose group (P>0.05); starting from the third day of the latency period, the escape latency time in the medium dose group was less than that in the WMI group (P<0.05). The medium and high dose groups crossed the platform more times than the WMI group (P<0.05). CONCLUSIONS: Low dose hUC-MSCs may yield unsatisfactory repair effects on WMI in neonatal rats, while medium and high doses of hUC-MSCs have significant repair effects, with the medium dose demonstrating superior efficacy.

A 78-year-old woman with diffuse white matter infiltration and predominant involvement of bilateral temporo-parieto-occipital regions.

Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (H3/IDH-wt-pHGG) is a newly defined entity amongst brain tumours, primarily reported in children. It is a rare, ill-defined type of tumour and the only method to diagnose it is DNA methylation profiling. The case we report here carries new knowledge about this tumour which may, in fact, occur in elderly patients, be devoid of evocative genomic abnormalities reported in children and harbour a misleading mutation.

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.

TIMP-3 Alleviates White Matter Injury After Subarachnoid Hemorrhage in Mice by Promoting Oligodendrocyte Precursor Cell Maturation.

Subarachnoid hemorrhage (SAH) is associated with high mortality and disability rates, and secondary white matter injury is an important cause of poor prognosis. However, whether brain capillary pericytes can directly affect the differentiation and maturation of oligodendrocyte precursor cells (OPCs) and subsequently affect white matter injury repair has still been revealed. This study was designed to investigate the effect of tissue inhibitor of metalloproteinase-3 (TIMP-3) for OPC differentiation and maturation. PDGFRßret/ret and wild-type C57B6J male mice were used to construct a mouse model of SAH via endovascular perforation in this study. Mice were also treated with vehicle, TIMP-3 RNAi or TIMP-3 RNAi + TIMP-3 after SAH. The effect of TIMP-3 on the differentiation and maturation of OPCs was determined using behavioral score, ELISA, transmission electron microscopy, immunofluorescence staining and cell culture. We found that TIMP-3 was secreted mainly by pericytes and that SAH and TIMP-3 RNAi caused a significant decrease in the TIMP-3 content, reaching a nadir at 24 h, followed by gradual recovery. In vitro, the myelin basic protein content of oligodendrocytes after oxyhemoglobin treatment was increased by TIMP-3 overexpression. The data indicates TIMP-3 could promote the differentiation and maturation of OPCs and subsequently improve neurological outcomes after SAH. Therefore, TIMP-3 could be beneficial for repair after white matter injury and could be a potential therapeutic target in SAH.

Predictors of multiple sclerosis progression: A systematic review of conventional magnetic resonance imaging studies.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic neurodegenerative disorder that affects the central nervous system (CNS) and results in progressive clinical disability and cognitive decline. Currently, there are no specific imaging parameters available for the prediction of longitudinal disability in MS patients. Magnetic resonance imaging (MRI) has linked imaging anomalies to clinical and cognitive deficits in MS. In this study, we aimed to evaluate the effectiveness of MRI in predicting disability, clinical progression, and cognitive decline in MS. METHODS: In this study, according to PRISMA guidelines, we comprehensively searched the Web of Science, PubMed, and Embase databases to identify pertinent articles that employed conventional MRI in the context of Relapsing-Remitting and progressive forms of MS. Following a rigorous screening process, studies that met the predefined inclusion criteria were selected for data extraction and evaluated for potential sources of bias. RESULTS: A total of 3028 records were retrieved from database searching. After a rigorous screening, 53 records met the criteria and were included in this study. Lesions and alterations in CNS structures like white matter, gray matter, corpus callosum, thalamus, and spinal cord, may be used to anticipate disability progression. Several prognostic factors associated with the progression of MS, including presence of cortical lesions, changes in gray matter volume, whole brain atrophy, the corpus callosum index, alterations in thalamic volume, and lesions or alterations in cross-sectional area of the spinal cord. For cognitive impairment in MS patients, reliable predictors include cortical gray matter volume, brain atrophy, lesion characteristics (T2-lesion load, temporal, frontal, and cerebellar lesions), white matter lesion volume, thalamic volume, and corpus callosum density. CONCLUSION: This study indicates that MRI can be used to predict the cognitive decline, disability progression, and disease progression in MS patients over time.

Distinct alterations in white matter properties and organization related to maternal treatment initiation in neonates exposed to HIV but uninfected.

HIV exposed-uninfected (HEU) infants and children are at risk of developmental delays as compared to HIV uninfected unexposed (HUU) populations. The effects of exposure to in utero HIV and ART regimens on the HEU the developing brain are not well understood. In a cohort of 2-week-old newborns, we used diffusion tensor imaging (DTI) tractography and graph theory to examine the influence of HIV and ART exposure in utero on neonate white matter integrity and organisation. The cohort included HEU infants born to mothers who started ART before conception (HEUpre) and after conception (HEUpost), as well as HUU infants from the same community. We investigated HIV exposure and ART duration group differences in DTI metrics (fractional anisotropy (FA) and mean diffusivity (MD)) and graph measures across white matter. We found increased MD in white matter connections involving the thalamus and limbic system in the HEUpre group compared to HUU. We further identified reduced nodal efficiency in the basal ganglia. Within the HEUpost group, we observed reduced FA in cortical-subcortical and cerebellar connections as well as decreased transitivity in the hindbrain area compared to HUU. Overall, our analysis demonstrated distinct alterations in white matter integrity related to the timing of maternal ART initiation that influence regional brain network properties.

Atypical brain structural connectivity and social cognition in childhood maltreatment and peer victimisation.

BACKGROUND: Childhood maltreatment (CM) is associated with neurobiological aberrations and atypical social cognition. Few studies have examined the neural effects of another common early-life interpersonal stressor, namely peer victimisation (PV). This study examines the associations between tract aberrations and childhood interpersonal stress from caregivers (CM) and peers (PV), and explores how the observed tract alterations are in turn related to affective theory of mind (ToM). METHODS: Data from 107 age-and gender-matched youths (34 CM [age = 19.9 ± 1.68; 36%male], 35 PV [age = 19.9 ± 1.65; 43%male], 38 comparison subjects [age = 20.0 ± 1.66; 42%male] were analysed using tractography and whole-brain tract-based spatial statistics (TBSS). RESULTS: At the whole-brain level using TBSS, the CM group had higher fractional anisotropy (FA) than the PV and comparison groups in a cluster of predominantly limbic and corpus callosal pathways. Segmented tractography indicated the CM group had higher FA in right uncinate fasciculus compared to both groups. They also had smaller right anterior thalamic radiation (ATR) tract volume than the comparison group and higher left ATR FA than the PV group, with these metrics associated with higher emotional abuse and enhanced affective ToM within the CM group, respectively. The PV group had lower inferior fronto-occipital fasciculus FA than the other two groups, which was related to lower affective ToM within the PV group. CONCLUSION: Findings suggest that exposure to early-life stress from caregivers and peers are differentially associated with alterations of neural pathways connecting the frontal, temporal and occipital cortices involved in cognitive and affective control, with possible links to their atypical social cognition.

Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

Outcome prediction of cardiac arrest with automatically computed gray-white matter ratio on computed tomography images.

BACKGROUND: This study aimed to develop an automated method to measure the gray-white matter ratio (GWR) from brain computed tomography (CT) scans of patients with out-of-hospital cardiac arrest (OHCA) and assess its significance in predicting early-stage neurological outcomes. METHODS: Patients with OHCA who underwent brain CT imaging within 12 h of return of spontaneous circulation were enrolled in this retrospective study. The primary outcome endpoint measure was a favorable neurological outcome, defined as cerebral performance category 1 or 2 at hospital discharge. We proposed an automated method comprising image registration, K-means segmentation, segmentation refinement, and GWR calculation to measure the GWR for each CT scan. The K-means segmentation and segmentation refinement was employed to refine the segmentations within regions of interest (ROIs), consequently enhancing GWR calculation accuracy through more precise segmentations. RESULTS: Overall, 443 patients were divided into derivation N=265, 60% and validation N=178, 40% sets, based on age and sex. The ROI Hounsfield unit values derived from the automated method showed a strong correlation with those obtained from the manual method. Regarding outcome prediction, the automated method significantly outperformed the manual method in GWR calculation (AUC 0.79 vs. 0.70) across the entire dataset. The automated method also demonstrated superior performance across sensitivity, specificity, and positive and negative predictive values using the cutoff value determined from the derivation set. Moreover, GWR was an independent predictor of outcomes in logistic regression analysis. Incorporating the GWR with other clinical and resuscitation variables significantly enhanced the performance of prediction models compared to those without the GWR. CONCLUSIONS: Automated measurement of the GWR from non-contrast brain CT images offers valuable insights for predicting neurological outcomes during the early post-cardiac arrest period.

The association between glymphatic system dysfunction and alterations in cerebral function and structure in patients with white matter hyperintensities.

The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.