White Matter Regions Research Articles

Pro-atherogenic medical conditions are associated with widespread regional brain metabolite abnormalities in those with alcohol use disorder.

Widespread brain metabolite abnormalities in those with alcohol use disorder (AUD) were reported in numerous studies, but the effects of the pro-atherogenic conditions of hypertension, type 2 diabetes mellitus, hepatitis C seropositivity, and hyperlipidemia on metabolite levels were not considered. These conditions were associated with brain metabolite abnormalities in those without AUD. We predicted treatment-seeking individuals with AUD and pro-atherogenic conditions (Atherogenic+) demonstrate lower regional metabolite markers of neuronal viability [N-acetylaspartate (NAA)] and cell membrane turnover/synthesis [choline-containing compounds (Cho)], compared with those with AUD without pro-atherogenic conditions (Atherogenic-) and healthy controls (CON). Atherogenic+ (n = 59) and Atherogenic- (n = 51) and CON (n = 49) completed a 1.5T proton magnetic resonance spectroscopic imaging study. Groups were compared on NAA, Cho, total creatine, and myoinositol in cortical gray matter (GM), white matter (WM), and select subcortical regions. Atherogenic+ had lower frontal GM and temporal WM NAA than CON. Atherogenic+ showed lower parietal GM, frontal, parietal and occipital WM and lenticular nuclei NAA level than Atherogenic- and CON. Atherogenic- showed lower frontal GM and WM NAA than CON. Atherogenic+ had lower Cho level than CON in the frontal GM, parietal WM, and thalamus. Atherogenic+ showed lower frontal WM and cerebellar vermis Cho than Atherogenic- and CON. Findings suggest proatherogenic conditions in those with AUD were associated with increased compromise of neuronal integrity and cell membrane turnover/synthesis. The greater metabolite abnormalities observed in Atherogenic+ may relate to increased oxidative stress-related compromise of neuronal and glial cell structure and/or impaired arterial vasoreactivity/lumen viability.

Development of Myelin Growth Charts of the White Matter Using T1 Relaxometry.

Myelin maturation occurs in late fetal life to early adulthood, with the most rapid changes observed in the first few years of infancy. To quantify the degree of myelination, a specific MR imaging sequence is required to measure the changes in tissue proton relaxivity (R1). R1 positively correlates with the degree of myelination maturation at a given age. Similar to head circumference charts, these data can be used to develop normal growth charts for specific white matter tracts to detect pathologies involving abnormal myelination. This is a cross-sectional study using normal clinical pediatric brain MR images with the MP2RAGE sequence to generate T1 maps. The T1 maps were segmented to 75 brain regions from a brain atlas (white matter and gyri). Statistical modeling for all subjects across regions and the age range was computed, and estimates of population-level percentile ranking were computed to describe the effective myelination rate as a function of age. Test-retest analysis was performed to assess reproducibility. Logistic trendline and regression were performed for selected white matter regions and plotted for growth charts. After exclusion for abnormal MR imaging or diseases affecting myelination from the electronic medical record, 103 subject MR images were included, ranging from birth to 17 years of age. Test-retest analysis resulted in a high correlation for white matter (r = 0.88) and gyri (r = 0.95). All white matter regions from the atlas had significant P values for logistic regression with R 2 values ranging from 0.41 to 0.99. These data can serve as a myelination growth chart to permit patient comparisons with normal levels with respect to age and brain regions, thus improving detection of developmental disorders affecting myelin.

Diffusion spectrum imaging in patients with idiopathic normal pressure hydrocephalus: correlation with ventricular enlargement

BackgroundTo investigate the association between white matter changes and ventricular expansion in idiopathic normal pressure hydrocephalus (iNPH) based on diffusion spectrum imaging (DSI).MethodsWe included 32 patients with iNPH who underwent DSI using a 3T MRI scanner. The lateral ventricles were manually segmented, and ventricular volumes were measured. Two methods were utilised in the study: manual region-of-interest (ROI) delineation and tract diffusion profile analysis. General fractional anisotropy (GFA) and fractional anisotropy (FA) were extracted in different white matter regions, including the bilateral internal capsule (anterior and posterior limbs) and corpus callosum (body, genu, and splenium) with manual ROI delineation. The 18 main tracts in the brain of each patient were extracted; the diffusion metrics of 100 equidistant nodes on each fibre were calculated, and Spearman’s correlation coefficient was used to determine the correlation between diffusion measures and ventricular volume of iNPH patients.ResultsThe GFA and FA of all ROI showed no significant correlation with lateral ventricular volume. However, in the tract diffusion profile analysis, lateral ventricular volume was positively correlated with part of the cingulum bundle, left corticospinal tract, and bilateral thalamic radiation posterior, whereas it was negatively correlated with the bilateral cingulum parahippocampal (all p < 0.05).ConclusionsThe effect of ventricular enlargement in iNPH on some white matter fibre tracts around the ventricles was limited and polarizing, and most white matter fibre tract integrity changes were not associated with ventricular enlargement; this reflects that multiple pathological mechanisms may have been combined to cause white matter alterations in iNPH.

Reflective imaging of myelin integrity in the human and mouse central nervous systems.

The structural integrity of myelin sheaths in the central nervous system (CNS) is crucial for the maintenance of its function. Electron microscopy (EM) is the gold standard for visualizing individual myelin sheaths. However, the tissue processing involved can induce artifacts such as shearing of myelin, which can be difficult to distinguish from true myelin abnormalities. Spectral confocal reflectance (SCoRe) microscopy is an imaging technique that leverages the differential refractive indices of compacted CNS myelin in comparison to surrounding parenchyma to detect individual compact myelin internodes with reflected light, positioning SCoRe as a possible complementary method to EM to assess myelin integrity. Whether SCoRe is sensitive enough to detect losses in myelin compaction when myelin quantity is otherwise unaffected has not yet been directly tested. Here, we assess the capacity of SCoRe to detect differences in myelin compaction in two mouse models that exhibit a loss of myelin compaction without demyelination: microglia-deficient mice (Csf1r-FIRE Δ/Δ) and wild-type mice fed with the CSF1R inhibitor PLX5622. In addition, we compare the ability to detect compact myelin sheaths using SCoRe in fixed-frozen versus paraffin-embedded mouse tissue. Finally, we show that SCoRe can successfully detect individual sheaths in aged human paraffin-embedded samples of deep white matter regions. As such, we find SCoRe to be an attractive technique to investigate myelin integrity, with sufficient sensitivity to detect myelin ultrastructural abnormalities and the ability to perform equally well in tissue preserved using different methods.

Microstructural properties in subacute aphasia: concurrent and prospective relationships underpinning recovery.

Few investigations examined the relationship between microstructural white matter integrity and subacute post-stroke linguistic performance or the relationship between microstructural integrity and the recovery of language function. We examined two key questions: (1) How does subacute language performance, measured in single words and discourse, relate to the microstructural integrity of key white matter regions of interest in the language network? and (2) Does the integrity of these regions before treatment predict the improvement or resolution of linguistic symptoms immediately and chronically following treatment? 58 participants within the first three months of stroke were enrolled in a randomized, single-center, double-blind, sham-controlled, study of anodal transcranial direct current stimulation combined with a computer-delivered speech and language naming therapy for subacute aphasia and were asked to complete magnetic resonance imaging at enrollment. Microstructural integrity was evaluated using diffusion tensor imaging processed with atlas-based segmentation. Regression and correlation analyses were conducted. A subset of 22 participants received diffusion tensor imaging. Picture naming accuracy significantly correlated with lower mean diffusivity (higher microstructural integrity) in the left posterior inferior temporal gyrus. Recovery of naming performance was predicted by days since stroke and baseline microstructural integrity of the left posterior middle temporal gyrus, arcuate fasciculus, and superior longitudinal fasciculus. Recovery of discourse efficiency was significantly predicted by the same model. This study demonstrates an association between picture naming and discourse and microstructural integrity of the key regions in the language network for patients with subacute post-stroke aphasia. Baseline microstructural integrity significantly predicts language recovery.

SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study.

The aim of this study was to investigate the impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET). In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups. A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] μmol ⋅ 100 g-1 ⋅ min-1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] μmol ⋅ 100 g-1 ⋅ min-1; P = 0.01), an effect observed in both gray and white matter regions. Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain.

Microstructural properties of attention-related white matter tracts are associated with the renewal effect of extinction

The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of BOLD activation in hippocampus, iFG and vmPFC, as well as differential resting-state functional connectivity between prefrontal regions and the dorsal attention network. Also, pharmacological modulations of the noradrenergic system that influence attentional processing have partially different effects upon individuals with (REN) and without (NoREN) a propensity for renewal. However, it is as yet unknown whether REN and NoREN individuals differ regarding microstructural properties in attention-related white matter (WM) regions, and whether such differences are related to noradrenergic processing. In this diffusion tensor imaging (DTI) analysis we investigated the relation between microstructural properties of attention-related WM tracts and ABA renewal propensity, under conditions of noradrenergic stimulation by means of the noradrenergic reuptake inhibitor atomoxetine, compared to placebo.Fractional anisotropy (FA) was higher in participants with noradrenergic stimulation (ATO) compared to placebo (PLAC), the effect was predominantly left-lateralized and based on the comparison of ATO REN and PLAC REN participants. In REN participants of both treatment groups, FA in several WM tracts showed a positive correlation with the ABA renewal level, suggesting higher renewal levels were associated with higher microstructural integrity. These findings point towards a relation between microstructural properties of attention-related WM tracts and the propensity for renewal that is not specifically dependent on noradrenergic processing.

Circadian rapid eye movement sleep expression is associated with brain microstructural integrity in older adults

Rapid eye movement sleep (REMS) is increasingly suggested as a discriminant sleep state for subtle signs of age-related neurodegeneration. While REMS expression is under strong circadian control and circadian dysregulation increases with age, the association between brain aging and circadian REMS regulation has not yet been assessed. Here, we measure the circadian amplitude of REMS through a 40-h in-lab multiple nap protocol in controlled laboratory conditions, and brain microstructural integrity with quantitative multi-parameter mapping (MPM) imaging in 86 older individuals. We show that reduced circadian REMS amplitude is related to lower magnetization transfer saturation (MTsat), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*) values in several white matter regions mostly located around the lateral ventricles, and with lower R1 values in grey matter clusters encompassing the hippocampus, parahippocampus, thalamus and hypothalamus. Our results further highlight the importance of considering circadian regulation for understanding the association between sleep and brain structure in older individuals.

Can gray matter loss in early adolescence be explained by white matter growth?

AbstractA fundamental puzzle about brain development is why the volume of gray matter (GM) apparently declines as white matter (WM) grows when children enter adolescence. Since pruned synapses are too small to affect GM volume, a prevailing theory posits that an expanded distribution of myelin causes the inner edge of the GM to “whiten” while total brain volume remains steady, shifting the MRI‐measured WM:GM boundary closer to the brain's outer surface. This theory inherently predicts that GM volume loss is concurrent with WM volume growth across regions, within sexes and over time, although these predictions have yet to be explicitly tested. In this study, we test these predictions by mapping regional GM and WM volumetric changes in 2333 participants of the Adolescent Brain Cognitive Development study aged 9–14 years who each received three MRI scans 2 years apart. We show that average GM and WM volume changes follow distinct spatial, temporal, and sex‐specific patterns, indicating that GM volume loss is not balanced by WM volume growth, although cortical GM thinning is weakly correlated with WM growth in some regions. We conclude that myelin is not the main source of measured GM volume loss, and we propose alternative candidates.

Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer's disease.

White matter hyperintensities (WMHs) are commonly detected on T2-weighted magnetic resonance imaging (MRI) scans, occurring in both typical aging and Alzheimer's disease. Despite their frequent appearance and their association with cognitive decline, the molecular factors contributing to WMHs remain unclear. In this study, we investigated the transcriptomic profiles of two commonly affected brain regions with coincident AD pathology-frontal subcortical white matter (frontal-WM) and occipital subcortical white matter (occipital-WM)-and compared with age-matched healthy controls. Through RNA-sequencing in frontal- and occipital-WM bulk tissues, we identified an upregulation of genes associated with brain vasculature function in AD white matter. To further elucidate vasculature-specific transcriptomic features, we performed RNA-seq analysis on blood vessels isolated from these white matter regions, which revealed an upregulation of genes related to protein folding pathways. Finally, comparing gene expression profiles between AD individuals with high- versus low-WMH burden showed an increased expression of pathways associated with immune function. Taken together, our study characterizes the diverse molecular profiles of white matter changes in AD compared to normal aging and provides new mechanistic insights processes underlying AD-related WMHs.

Tensor-valued diffusion MRI detects brain microstructure changes in HIV infected individuals with cognitive impairment.

Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination antiretroviral therapy) irreversible brain injury. People with HIV (PWH) treated with cART do not show significant neurocognitive changes over relatively short follow-up periods. However, quantitative neuroimaging may be able to detect ongoing subtle microstructural changes. This study aimed to investigate the sensitivity of tensor-valued diffusion encoding in detecting such changes in brain microstructural integrity in cART-treated PWH. Additionally, it explored relationships between these metrics, neurocognitive scores, and plasma levels of neurofilament light (NFL) chain and glial fibrillary acidic protein (GFAP). Using MRI at 3T, 24 PWH and 31 healthy controls underwent cross-sectional examination. The results revealed significant variations in b-tensor encoding metrics across white matter regions, with associations observed between these metrics, cognitive performance, and blood markers of neuronal and glial injury (NFL and GFAP). Moreover, a significant interaction between HIV status and imaging metrics was observed, particularly impacting total cognitive scores in both gray and white matter. These findings suggest that b-tensor encoding metrics offer heightened sensitivity in detecting subtle changes associated with axonal injury in HIV infection, underscoring their potential clinical relevance in understanding neurocognitive impairment in PWH.

Automatic lesion detection at Multiple Sclerosis patients – Comparison of 2D- and 3D-FLAIR-datasets

BackgroundMultiple Sclerosis (MS) is a common autoimmune inflammatory disease of the central nervous system (CNS). Magnetic Resonance Imaging (MRI) allows a sensitive assessment of the CNS and is established for diagnostic, prognostic and (therapy-) monitoring purposes. Especially lesion counting in T2- or Fluid Attenuated Inversion Recovery (FLAIR)-weighted images plays a decisive role in clinical routine. Software-packages allowing an automatic evaluation of image data are increasingly established aiming a faster and improved workflow. These programs allow e.g. the counting, spatial attribution and volumetry of MS-lesions in FLAIR-weighted images. Research has shown that 3D-FLAIR-sequences are superior to 2D-FLAIR-sequences in visual evaluation of lesion burden in MS. An influence on the automatic analysis is expectable but not yet systematically studied. This work will therefore investigate the influence of 2D- and 3D datasets on the results of an automatic assessment. Material and methodsIn this prospective study, 80 Multiple Sclerosis patients underwent a clinically indicated routine MRI examination. The clinical routine protocol already including a 3D-FLAIR sequence was adapted by an additional 2D-FLAIR sequence also conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. To obtain a quantitative analysis for assessment of amount, dissemination and volume of the lesions, the acquired MR images were post-processed using the CE-certified Software mdbrain (mediaire, Berlin, Germany). The resulting data were statistically analysed using the paired t-test for normally distributed data and the Wilcoxon-signed-rank-test for not normally distributed data respectively. Demographic data and data such as the subtype, duration, severity and therapy of the disease were collected, pseudonymized and evaluated. ResultsThere is a significant difference concerning the total number and lesion volume with more lesions being detected (2D: 29.7, +/- 20.22 sd; 3D: 40.1 +/- 31.67 sd; p < 0.0001) but lower total volume (2D: 6.24 +/- 6.11 sd; 3D: 5.39 +/- 6.37 sd; p < 0.0001) when using the 3D- sequence. Especially significantly more small lesions in the unspecific white matter and infratentorial region were detected by using the 3D-FLAIR sequence (p < 0.0001) compared to the 2D-FLAIR image. Main reason for the lower total volume in the 3D-FLAIR sequence was the calculated volume for periventricular lesions which was significantly beneath the calculated volume from the 2D-FLAIR sequence (p < 0.0001). ConclusionAutomatic lesion counting and volumetry is feasible with both 2D- and 3D-weightend FLAIR images. Still, it leads to partly significant differences even between two sequences that both are conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. This study contributes valuable insights into the impact of using different input data from the same patient for automated MS lesion evaluation.

A Pilot Study Investigating the Use of Serum Glial Fibrillary Acidic Protein to Monitor Changes in Brain White Matter Integrity After Repetitive Head Hits During a Single Collegiate Football Game.

Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurological outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after nonconcussive RHHs during a single sporting contest, raising the possibility that they could be used in real time to monitor the brain's early response to repeated asymptomatic head hits. To test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 min (T2) after a single collegiate football game in 30 athletes. Glial fibrillary acidic protein (GFAP) changes were correlated with three measures of head impact exposure (number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors) and to changes in brain white matter (WM) integrity, estimated by regional changes in fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging from 24 h before (T1) to 48 h after (T3) the game. To account for the potentially confounding effects of physical exertion on GFAP, correlations were adjusted for kilocalories of energy expended during the game measured by wearable body sensors. All 30 participants were male with a mean age of 19.5 ± 1.2 years. No participant had a concussion during the index game. We observed a significant increase in GFAP from T0 to T1 (mean 79.69 vs. 91.95 pg/mL, p = 0.008) and from T0 to T2 (mean 79.69 vs. 99.21 pg/mL, p < 0.001). WM integrity decreased in multiple WM regions but was statistically significant in the right fornix (mean % FA change -1.43, 95% confidence interval [CI]: -2.20, -0.66). T0 to T2 increases in GFAP correlated with reduced FA in the left fornix, right fornix, and right medical meniscus and with increased MD in the right fornix (r-values ranged from 0.59 to 0.61). Adjustment for exertion had minimal effect on these correlations. GFAP changes did not correlate to head hit exposure, but after adjustment for exertion, T0 to T2 increases correlated with all three hit metrics (r-values ranged from 0.69 to 0.74). Thus, acute elevations in GFAP after a single collegiate football game of RHHs correlated with in-game head hit exposure and with reduced WM integrity 2 days later. These results suggest that GFAP may be a biologically relevant indicator of the brain's early response to RHHs during a single sporting event. Developing tools to measure the neurological response to RHHs on an individual level has the potential to provide insight into the heterogeneity in adverse outcomes after RHH exposure and for developing effective and personalized countermeasures. Owing to the small sample size, these findings should be considered preliminary; validation in a larger, independent cohort is necessary.

Distinct origin and region-dependent contribution of stromal fibroblasts to fibrosis following traumatic injury in mice

Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal fibroblasts forming the fibrotic scar derive from two populations of perivascular cells after spinal cord injury (SCI) in adult mice of both sexes. We anatomically and transcriptionally identify the two cell populations as pericytes and perivascular fibroblasts. Fibroblasts and pericytes are enriched in the white and gray matter regions of the spinal cord, respectively. Both cell populations are recruited in response to SCI and inflammation. However, their contribution to fibrotic scar tissue depends on the location of the lesion. Upon injury, pericytes and perivascular fibroblasts become activated and transcriptionally converge on the generation of stromal myofibroblasts. Our results show that pericytes and perivascular fibroblasts contribute to the fibrotic scar in a region-dependent manner.

Structural white matter abnormalities in Schizophrenia and associations with neurocognitive performance and symptom severity

Schizophrenia is associated with robust white matter (WM) abnormalities but influences of potentially confounding variables and relationships with cognitive performance and symptom severity remain to be fully determined. This study was designed to evaluate WM abnormalities based on diffusion tensor imaging (DTI) in individuals with schizophrenia, and their relationships with cognitive performance and symptom severity. Data from individuals with schizophrenia (SZ; n=138, mean age±SD=39.02±11.82; 105 males) and healthy controls (HC; n=143, mean age±SD=37.07±10.84; 102 males) were collected as part of the Function Biomedical Informatics Research Network Phase 3 study. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were compared between individuals with schizophrenia and healthy controls, and their relationships with neurocognitive performance and symptomatology assessed. Individuals with SZ had significantly lower FA in forceps minor and the left inferior fronto-occipital fasciculus compared to HC. FA in several tracts were associated with speed of processing and attention/vigilance and the severity of the negative symptom alogia. This study suggests that regional WM abnormalities are fundamentally involved in the pathophysiology of schizophrenia and may contribute to cognitive performance deficits and symptom expression observed in schizophrenia.

Quantitative cellular pathology of the amygdala in temporal lobe epilepsy and correlation with magnetic resonance imaging volumetry, tissue microstructure, and sudden unexpected death in epilepsy risk factors.

Amygdala enlargement can occur in temporal lobe epilepsy, and increased amygdala volume is also reported in sudden unexpected death in epilepsy (SUDEP). Apnea can be induced by amygdala stimulation, and postconvulsive central apnea (PCCA) and generalized seizures are both known SUDEP risk factors. Neurite orientation dispersion and density imaging (NODDI) has recently provided additional information on altered amygdala microstructure in SUDEP. In a series of 24 surgical temporal lobe epilepsy cases, our aim was to quantify amygdala cellular pathology parameters that could predict enlargement, NODDI changes, and ictal respiratory dysfunction. Using whole slide scanning automated quantitative image analysis methods, parallel evaluation of myelin, axons, dendrites, oligodendroglia, microglia, astroglia, neurons, serotonergic networks, mTOR-pathway activation (pS6) and phosphorylated tau (pTau; AT8, AT100, PHF) in amygdala, periamygdala cortex, and white matter regions of interest were compared with preoperative magnetic resonance imaging data on amygdala size, and in 13 cases with NODDI and evidence of ictal-associated apnea. We observed significantly higher glial labeling (Iba1, glial fibrillary acidic protein, Olig2) in amygdala regions compared to cortex and a strong positive correlation between Olig2 and Iba1 in the amygdala. Larger amygdala volumes correlated with lower microtubule-associated protein (MAP2), whereas higher NODDI orientation dispersion index correlated with lower Olig2 cell densities. In the three cases with recorded PCCA, higher MAP2 and pS6-235 expression was noted than in those without. pTau did not correlate with SUDEP risk factors, including seizure frequency. Histological quantitation of amygdala microstructure can shed light on enlargement and diffusion imaging alterations in epilepsy to explore possible mechanisms of amygdala dysfunction, including mTOR pathway activation, that in turn may increase the risk for SUDEP.

Biophysical modeling and diffusion kurtosis imaging reveal microstructural alterations in normal-appearing white-matter regions of the brain in obstructive sleep apnea.

Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA. Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers. OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort. Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia.

Rich-club organization of whole-brain spatio-temporal multilayer functional connectivity networks

ObjectiveIn this work, we propose a novel method for constructing whole-brain spatio-temporal multilayer functional connectivity networks (FCNs) and four innovative rich-club metrics.MethodsSpatio-temporal multilayer FCNs achieve a high-order representation of the spatio-temporal dynamic characteristics of brain networks by combining the sliding time window method with graph theory and hypergraph theory. The four proposed rich-club scales are based on the dynamic changes in rich-club node identity, providing a parameterized description of the topological dynamic characteristics of brain networks from both temporal and spatial perspectives. The proposed method was validated in three independent differential analysis experiments: male–female gender difference analysis, analysis of abnormality in patients with autism spectrum disorders (ASD), and individual difference analysis.ResultsThe proposed method yielded results consistent with previous relevant studies and revealed some innovative findings. For instance, the dynamic topological characteristics of specific white matter regions effectively reflected individual differences. The increased abnormality in internal functional connectivity within the basal ganglia may be a contributing factor to the occurrence of repetitive or restrictive behaviors in ASD patients.ConclusionThe proposed methodology provides an efficacious approach for constructing whole-brain spatio-temporal multilayer FCNs and conducting analysis of their dynamic topological structures. The dynamic topological characteristics of spatio-temporal multilayer FCNs may offer new insights into physiological variations and pathological abnormalities in neuroscience.

Regional Brain Net Water Uptake in Computed Tomography after Cardiac Arrest – A Novel Biomarker for Neuroprognostication

BackgroundSelective water uptake by neurons and glial cells and subsequent brain tissue oedema are key pathophysiological processes of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Although brain computed tomography (CT) is widely used to assess the severity of HIE, changes of brain radiodensity over time have not been investigated. These could be used to quantify regional brain net water uptake (NWU), a potential prognostic biomarker. MethodsWe conducted an observational prognostic accuracy study including a derivation (single center cardiac arrest registry) and a validation (international multicenter TTM2 trial) cohort. Early (<6 h) and follow-up (>24 h) head CTs of CA patients were used to determine regional NWU for grey and white matter regions after co-registration with a brain atlas. Neurological outcome was dichotomized as good versus poor using the Cerebral Performance Category Scale (CPC) in the derivation cohort and Modified Rankin Scale (mRS) in the validation cohort. ResultsWe included 115 patients (81 derivation, 34 validation) with out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Regional brain water content remained unchanged in patients with good outcome. In patients with poor neurological outcome, we found considerable regional water uptake with the strongest effect in the basal ganglia. NWU >8% in the putamen and caudate nucleus predicted poor outcome with 100% specificity (95%-CI: 86–100%) and 43% (moderate) sensitivity (95%-CI: 31–56%). ConclusionThis pilot study indicates that NWU derived from serial head CTs is a promising novel biomarker for outcome prediction after CA. NWU >8% in basal ganglia grey matter regions predicted poor outcome while absence of NWU indicated good outcome. NWU and follow-up CTs should be investigated in larger, prospective trials with standardized CT acquisition protocols.

Understanding the impact of congenital infections and perinatal viral exposures on the developing brain using white matter magnetic resonance imaging: a scoping review

BackgroundMagnetic Resonance Imaging (MRI)-based imaging techniques are useful for assessing white matter (WM) structural and microstructural integrity in the context of infection and inflammation. The purpose of this scoping review was to assess the range of work on the use of WM neuroimaging approaches to understand the impact of congenital and perinatal viral infections or exposures on the developing brain.MethodsThis scoping review was conducted according to the Arksey and O’ Malley framework. A literature search was performed in Web of Science, Scopus and PubMed for primary research articles published from database conception up to January 2022. Studies evaluating the use of MRI-based WM imaging techniques in congenital and perinatal viral infections or exposures were included. Results were grouped by age and infection.ResultsA total of 826 articles were identified for screening and 28 final articles were included. Congenital and perinatal infections represented in the included studies were cytomegalovirus (CMV) infection (n = 12), human immunodeficiency virus (HIV) infection (n = 11) or exposure (n = 2) or combined (n = 2), and herpes simplex virus (HSV) infection (n = 1). The represented MRI-based WM imaging methods included structural MRI and diffusion-weighted and diffusion tensor MRI (DWI/ DTI). Regions with the most frequently reported diffusion metric group differences included the cerebellar region, corticospinal tract and association fibre WM tracts in both children with HIV infection and children who are HIV-exposed uninfected. In qualitative imaging studies, WM hyperintensities were the most frequently reported brain abnormality in children with CMV infection and children with HSV infection.ConclusionThere was evidence that WM imaging techniques can play a role as diagnostic and evaluation tools assessing the impact of congenital infections and perinatal viral exposures on the developing brain. The high sensitivity for identifying WM hyperintensities suggests structural brain MRI is a useful neurodiagnostic modality in assessing children with congenital CMV infection, while the DTI changes associated with HIV suggest metrics such as fractional anisotropy have the potential to be specific markers of subtle impairment or WM damage in neuroHIV.