Deep White Matter Research Articles

Assessing Cerebral Microvascular Volumetric Pulsatility with High-Resolution 4D CBV MRI at 7T.

Arterial pulsation is crucial for promoting fluid circulation and for influencing neuronal activity. Previous studies assessed the pulsatility index based on blood flow velocity pulsatility in relatively large cerebral arteries of human. Here, we introduce a novel method to quantify the volumetric pulsatility of cerebral microvasculature across cortical layers and in white matter (WM), using high-resolution 4D vascular space occupancy (VASO) MRI with simultaneous recording of pulse signals at 7T. Microvascular volumetric pulsatility index (mvPI) and cerebral blood volume (CBV) changes across cardiac cycles are assessed through retrospective sorting of VASO signals into cardiac phases and estimating mean CBV in resting state (CBV0) by arterial spin labeling (ASL) MRI at 7T. Using data from 11 young (28.4±5.8 years) and 7 older (61.3±6.2 years) healthy participants, we investigated the aging effect on mvPI and compared microvascular pulsatility with large arterial pulsatility assessed by 4D-flow MRI. We observed the highest mvPI in the cerebrospinal fluid (CSF) on the cortical surface (0.19±0.06), which decreased towards the cortical layers as well as in larger arteries. In the deep WM, a significantly increased mvPI (p = 0.029) was observed in the older participants compared to younger ones. Additionally, mvPI in deep WM is significantly associated with the velocity pulsatility index (vePI) of large arteries (r = 0.5997, p = 0.0181). We further performed test-retest scans, non-parametric reliability test and simulations to demonstrate the reproducibility and accuracy of our method. To the best of our knowledge, our method offers the first in vivo measurement of microvascular volumetric pulsatility in human brain which has implications for cerebral microvascular health and its relationship research with glymphatic system, aging and neurodegenerative diseases.

White matter structural bases for phase accuracy during tapping synchronization.

We determined the intersubject association between the rhythmic entrainment abilities of human subjects during a synchronization-continuation tapping task (SCT) and the macro- and microstructural properties of their superficial (SWM) and deep (DWM) white matter. Diffusion-weighted images were obtained from 32 subjects who performed the SCT with auditory or visual metronomes and five tempos ranging from 550 to 950 ms. We developed a method to determine the density of short-range fibers that run underneath the cortical mantle, interconnecting nearby cortical regions (U-fibers). Notably, individual differences in the density of U-fibers in the right audiomotor system were correlated with the degree of phase accuracy between the stimuli and taps across subjects. These correlations were specific to the synchronization epoch with auditory metronomes and tempos around 1.5 Hz. In addition, a significant association was found between phase accuracy and the density and bundle diameter of the corpus callosum (CC), forming an interval-selective map where short and long intervals were behaviorally correlated with the anterior and posterior portions of the CC. These findings suggest that the structural properties of the SWM and DWM in the audiomotor system support the tapping synchronization abilities of subjects, as cortical U-fiber density is linked to the preferred tapping tempo and the bundle properties of the CC define an interval-selective topography.

Glymphatic System Impairment in the Advanced Stage of Moyamoya Disease.

Assessing the glymphatic system activity using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS) may be helpful to understand the pathophysiology of moyamoya disease (MMD). 63 adult patients with MMD and 20 healthy controls (HCs) were included for T1-weighted images, T2-FLAIR, pseudocontinuous arterial spin labeling, and DTI. 60 patients had digital subtraction angiography more than 6 months after combined revascularization. The Suzuki stage, postoperative Matsushima grade, periventricular anastomoses (PA), enlarged perivascular spaces (EPVS), deep and subcortical white matter hyperintensities (DSWMH), DTI-ALPS, cerebral blood flow (CBF), and cognitive scales of MMD patients were assessed. MMD patients were divided into early and advanced stage based on the Suzuki stage. We detected lower DTI-ALPS in patients with advanced stage relative to HCs (p = 0.046) and patients with early stage (p = 0.004), hemorrhagic MMD compared with ischemic MMD (p = 0.048), and PA Grade 2 compared with Grade 0 (p = 0.010). DTI-ALPS was correlated with the EPVS in basal ganglia (r = -0.686, p < 0.001), Suzuki stage (r = -0.465, p < 0.001), DSWMH (r = -0.423, p = 0.001), and global CBF (r = 0.300, p = 0.017) and cognitive scores (r = 0.343, p = 0.018). The DTI-ALPS of patients with good postoperative collateral formation was higher compared to those with poor postoperative collateral formation (p = 0.038). In conclusion, the glymphatic system was impaired in advanced MMD patients and may affected cognitive function and postoperative neoangiogenesis.

Detailed delineation of the fetal brain in diffusion MRI via multi-task learning.

Diffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain inutero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable. The lack of automated methods for fast, accurate, and reproducible data analysis has seriously limited our ability to tap the potential of fetal brain dMRI for medical and scientific applications. In this work, we developed and validated a unified computational framework to (1) segment the brain tissue into white matter, cortical/subcortical gray matter, and cerebrospinal fluid, (2) segment 31 distinct white matter tracts, and (3) parcellate the brain's cortex and delineate the deep gray nuclei and white matter structures into 96 anatomically meaningful regions. We utilized a set of manual, semi-automatic, and automatic approaches to annotate 97 fetal brains. Using these labels, we developed and validated a multi-task deep learning method to perform the three computations. Our evaluations show that the new method can accurately carry out all three tasks, achieving a mean Dice similarity coefficient of 0.865 on tissue segmentation, 0.825 on white matter tract segmentation, and 0.819 on parcellation. The proposed method can greatly advance the field of fetal neuroimaging as it can lead to substantial improvements in fetal brain tractography, tract-specific analysis, and structural connectivity assessment.

Clinical and neuroradiological spectrum of biallelic variants in NOTCH3

NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), patients with biallelic variants in NOTCH3 are extremely rare and not well characterised. In this study, we present clinical and genetic data from 25 patients with biallelic NOTCH3 variants and conduct a literature review of another 25 cases (50 patients in total). Brain magnetic resonance imaging (MRI) were analysed by expert neuroradiologists to better understand the phenotype associated with biallelic NOTCH3 variants. Our systematic analyses verified distinct genotype-phenotype correlations for the two types of biallelic variants in NOTCH3. Biallelic loss-of-function variants (26 patients) lead to a neurodevelopmental disorder characterised by spasticity, childhood-onset stroke, and periatrial white matter volume loss resembling periventricular leukomalacia. Conversely, patients with biallelic cysteine-involving missense variants (24 patients) fall within CADASIL spectrum phenotype with early adulthood onset stroke, dementia, and deep white matter lesions without significant volume loss. White matter lesion volume is comparable between patients with biallelic cysteine-involving missense variants and individuals with CADASIL. Notably, monoallelic carriers of loss-of-function variants are predominantly asymptomatic, with only a few cases reporting nonspecific headaches. We propose a NOTCH3-SVD classification depending on dosage and variant type. This study not only expands our knowledge of biallelic NOTCH3 variants but also provides valuable insight into the underlying mechanisms of the disease, contributing to a more comprehensive understanding of NOTCH3-related SVD. The Wellcome Trust, the MRC.

A case of MERS presenting with acute motor aphasia and tetraparesis and literature review

BackgroundMild encephalopathy wıth reversible splenial lesions (MERS) are a clinical–radiological diagnosis that can be diagnosed with radiological imaging and can be accompanied by impaired consciousness, aphasia, headache, and paralysis. MERS can be divided into two different types based on radiological findings; Involvement of the splenium is seen in type 1, and involvement of the splenium and deep white matter is seen in type 2. MERS Type 2 is very rare in adults. Here, we describe a patient diagnosed with MERS Type 2 and our therapeutic intervention.Case presentationA 22-year-old woman presented with slurred speech, weakness in the extremities and headache that started 14 h ago. The patient had sore throat and fever of 37.6 °C for 2 days, and medical history or family history were unremarkable. Neurological examination revealed that she was conscious, cooperative, with no signs of meningeal irritation. Speech comprehension, naming, and repetition were preserved, motor examination revealed 5/5 left upper extremity strength, 4/5 right upper extremity strength, and 2/5 bilateral lower extremity strength. Diffusion-weighted magnetic resonance imaging (MRI-DWI) revealed bilateral deep white matter and splenium symmetrical diffusion restriction. Blood tests showed high C-reactive protein (CRP) and no leukocytosis. No cells were detected in the cerebrospinal fluid (CSF), protein was 151 mg/dl, glucose was within normal limits. The patient, who developed quadriparesis during follow-up, was started on pulse dose steroids. Neurological examination improved to patient’s baseline at the 12th hour of treatment. In the 72nd hour control MRI-DWI, it was seen that the lesions had regressed. Culture/Polymerase chain reaction (PCR) for bacterial/viral infection agents came back negative. After steroids were given for 5 days, patient was discharged at her baseline.ConclusionsMERS is a rare diagnosis in adults and can be radiologically confused with acute toxic leukoencephalopathy. It can be distinguished clinically by the absence of prior infection, fever, and toxic agent exposure. Although there is no consensus in the literature regarding the treatment, the clinical picture improved rapidly after steroid in our case. Despite being rare, it should be considered in the differential diagnosis of patients with deep white matter lesions in adults.

Effects of post-acute COVID-19 syndrome on cerebral white matter and emotional health among non-hospitalized individuals.

Post-acute COVID syndrome (PACS) is a growing concern, given its impact on mental health and quality of life. However, its effects on cerebral white matter remain poorly understood, particularly in non-hospitalized cohorts. The goals of this cross-sectional, observational study were to examine (1) whether PACS was associated with distinct alterations in white matter microstructure, compared to symptom-matched non-COVID viral infection; and (2) whether microstructural alterations correlated with indices of post-COVID emotional health. Data were collected for 54 symptomatic individuals who tested positive for COVID-19 (mean age 41 ± 12 yrs., 36 female) and 14 controls who tested negative for COVID-19 (mean age 41 ± 14 yrs., 8 female), with both groups assessed an average of 4-5 months after COVID testing. Diffusion magnetic resonance imaging data were collected, and emotional health was assessed via the NIH emotion toolbox, with summary scores indexing social satisfaction, well-being and negative affect. Despite similar symptoms, the COVID-19 group had reduced mean and axial diffusivity, along with increased mean kurtosis and neurite dispersion, in deep white matter. After adjusting for social satisfaction, higher levels of negative affect in the COVID-19 group were also correlated with increased mean kurtosis and reduced free water in white matter. These results provide preliminary evidence that indices of white matter microstructure distinguish PACS from symptomatic non-COVID infection. Moreover, white matter effects seen in PACS correlate with the severity of emotional sequelae, providing novel insights into this highly prevalent disorder.

Impact of Systolic Blood Viscosity on Deep White Matter Hyperintensities in Patients With Acute Ischemic Stroke.

Elevated blood viscosity (BV), a critical determinant in blood rheology, is a contributing factor in cerebrovascular diseases. The specific influence of BV on small vessel disease burden remains unexplored. This study aims to examine the relationship between BV and regional white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. We enrolled a cohort of 302 patients with acute ischemic stroke or transient ischemic attack who were admitted to a hospital within 7 days of symptom onset in this study. We measured whole BV using a scanning capillary-tube viscometer and categorized systolic blood viscosity into 3 groups based on established references. We quantified and normalized WMH volumes using automated localization and segmentation software by NEUROPHET Inc. We performed multivariable logistic regression analysis to assess the correlation between systolic BV and WMH. The mean subject age was 66.7±13.4 years, and 38.7% (n=117) of the participants were female. Among a total of 302 patients, patients with higher deep WMH volume (T3) were typically older and had an atrial fibrillation, strokes of cardioembolic or undetermined cause, elevated levels of C-reactive protein, diastolic blood viscosity and systolic BV. A multivariable adjustment revealed a significant association between high systolic BV and increased deep-WMH volume (odds ratio [OR], 2.636 [95% CI, 1.225-5.673]). Elevated systolic BV is more likely to be associated with deep WMH volume in patients with acute ischemic stroke or transient ischemic attack. These findings reveal novel therapeutic strategies focusing on blood rheology to enhance cerebral microcirculation in stroke management.

Assessing Relative Linguistic Impairment With Model-Based Item Selection.

A picture naming test is presented that reveals impairment to specific mechanisms involved in the naming process, using accuracy scores on curated item sets. A series of psychometric validation experiments are reported. Using a computational model that enables estimation of item difficulty at the lexical and sublexical stages of word retrieval, two complimentary sets of items were constructed that challenge the respective psycholinguistic levels of representation. The difference in accuracy between these item sets yields the relative linguistic impairment (RLI) score. In a cohort of 91 people with chronic left-hemisphere stroke who enrolled in a clinical trial for anomia, we assessed psychometric properties of the RLI score and then used the new scale to make predictions about other language behaviors, lesion distributions, and functional activation during naming. RLI scores had adequate psychometric properties for clinical significance. RLI scores contained predictive information about spontaneous speech fluency, over and above accuracy. A dissociation was observed between performance on the RLI item sets and performance on the subtests of an independent language battery. Sublexical RLI was significantly associated with apraxia of speech and with lesions encompassing perisylvian regions, while lexical RLI was associated with lesions to deep white matter. The RLI construct was reflected in functional brain activity during naming, independent of overall accuracy, with a respective shift of activation between dorsal and ventral networks responsible for different aspects of word retrieval. The RLI assessment satisfies the psychometric requirements to serve as a useful clinical measure.

Brain Diffusion Changes in Perinatal Asphyxia Cases.

Prolonged perinatal asphyxia (PA) may cause hypoxic-ischemic damage to the brain. The aim of this study was to investigate the brain diffusion changes of patients with PA and examine the relationship with brain damage. This retrospective study included 55 patients diagnosed with PA, separated into mild and severe PA groups. For the evaluation of brain damage in all the study neonates, brain and diffusion MRI scans were performed using a 3T device. The scans were taken between 5 and 10 days postnatal, after completion of hypothermia treatment, in accordance with the standard clinical protocol of our institution. Apparent diffusion coefficient (ADC) values of the lentiform nucleus, thalamus, frontal white matter, and posterior limbs of the internal capsule were measured. Minitab package programs and SPSS version 20.0 software were used for statistical analysis and graphic drawing. Spearman's rank correlation analysis was used. The bilateral lentiform nucleus, thalamus, frontal white matter, and posterior limbs of the internal capsule ADC values were significantly higher in the severe PA group than in the mild PA group. In neonates with severe perinatal asphyxia, brain damage can be evaluated on diffusion-weighted imaging (DWI) of the cerebral deep white matter and basal ganglia. DWI, imaging with conventional brain MRI comes to the fore in clinical importance in PA patients.

The relationship between intracranial atherosclerosis and white matter hyperintensity in ischemic stroke patients: a retrospective cross-sectional study using high-resolution magnetic resonance vessel wall imaging.

Both intracranial atherosclerosis and white matter hyperintensity (WMH) are prevalent among the stroke population. However, the relationship between intracranial atherosclerosis and WMH has not been fully elucidated. Therefore, the aim of this study was to investigate the relationship between the characteristics of intracranial atherosclerotic plaques and the severity of WMH in patients with ischemic stroke using high-resolution magnetic resonance vessel wall imaging. Patients hospitalized with ischemic stroke and concurrent intracranial atherosclerosis at Beijing Tsinghua Changgung Hospital, a tertiary comprehensive stroke center, who underwent high-resolution magnetic resonance vessel wall imaging and conventional brain magnetic resonance imaging were continuously recruited from January 2018 to December 2018. Both intracranial plaque characteristics (plaque number, maximum wall thickness, luminal stenosis, T1 hyperintensity, and plaque length) and WMH severity (Fazekas score and volume) were evaluated. Spearman correlation or point-biserial correlation analysis was used to determine the association between clinical characteristics and WMH volume. The independent association between intracranial plaque characteristics and the severity as well as WMH score was analyzed using logistic regression. The associations of intracranial plaque characteristics with total white matter hyperintensity (TWMH) volume, periventricular white matter hyperintensity (PWMH) volume and deep white matter hyperintensity (DWMH) volume were determined using multilevel mixed-effects linear regression. A total of 159 subjects (mean age: 64.0±12.5 years; 103 males) were included into analysis. Spearman correlation analysis indicated that age was associated with TWMH volume (r=0.529, P<0.001), PWMH volume (r=0.523, P<0.001) and DWMH volume (r=0.515, P<0.001). Point-biserial correlation analysis indicated that smoking (r=-0.183, P=0.021) and hypertension (r=0.159, P=0.045) were associated with DWMH volume. After adjusting for confounding factors, logistic regression analysis showed plaque number was significantly associated with the presence of severe WMH [odds ratio (OR), 1.590; 95% CI, 1.241-2.035, P<0.001], PWMH score of 3 (OR, 1.726; 95% CI, 1.074-2.775, P=0.024), and DWMH score of 2 (OR, 1.561; 95% CI, 1.150-2.118, P=0.004). Intracranial artery luminal stenosis was associated with presence of severe WMH (OR, 1.032; 95% CI, 1.002-1.064, P=0.039) and PWMH score of 2 (OR, 1.057; 95% CI, 1.008-1.109, P=0.023). Multilevel mixed-effects linear regression analysis showed that plaque number was associated with DWMH volume (β=0.128; 95% CI, 0.016-0.240; P=0.026) after adjusted for age and sex. In ischemic stroke patients, intracranial atherosclerotic plaque characteristics as measured by plaque number and luminal stenosis were associated with WMH burden.

Evaluation of microstructural brain changes in post-coronavirus disease 2019 (COVID-19) patients with neurological symptoms: a cross-sectional study.

Changes in both the vascular system and brain tissues can occur after a prior episode of coronavirus disease 2019 (COVID-19), detectable through modifications in diffusion parameters using magnetic resonance imaging (MRI) techniques. These changes in diffusion parameters may be particularly prominent in highly organized structures such as the corpus callosum (CC), including its major components, which have not been adequately studied following COVID-19 infection. Therefore, the study aimed to evaluate microstructural changes in whole-brain (WB) diffusion, with a specific focus on the CC. A total of 101 probands (age range from 18 to 69 years) participated in this retrospective study, consisting of 55 volunteers and 46 post-COVID-19 patients experiencing neurological symptoms. The participants were recruited from April 2022 to September 2023 at the Institute for Clinical and Experimental Medicine in Prague, Czech Republic. All participants underwent MRI examinations on a 3T MR scanner with a diffusion protocol, complemented by additional MRI techniques. Two volunteers and five patients were excluded from the study due to motion artefacts, severe hypoperfusion or the presence of lesions. Participants were selected by a neurologist based on clinical examination and a serological test for COVID-19 antibodies. They were then divided into three groups: a control group of healthy volunteers (n=28), an asymptomatic group (n=25) with a history of infection but no symptoms, and a symptomatic group (n=41) with a history of COVID-19 and neurological symptoms. Symptomatic patients did not exhibit neurological symptoms before contracting COVID-19. Diffusion data underwent eddy current and susceptibility distortion corrections, and fiber tracking was performed using default parameters in DSI studio. Subsequently, various diffusion metrics, were computed within the reconstructed tracts of the WB and CC. To assess the impact of COVID-19 and its associated symptoms on diffusion indices within the white matter of the WB and CC regions, while considering age, we employed a statistical analysis using a linear mixed-effects model within the R framework. Statistical analysis revealed a significant difference in mean diffusivity (MD) between the symptomatic and control groups in the forceps minor (P=0.001) and CC body (P=0.003). In addition to changes in diffusion, alterations in brain perfusion were observed in two post-COVID-19 patients who experienced a severe course. Furthermore, hyperintense lesions were identified in subcortical and deep white matter areas in the vast majority of symptomatic patients. The main finding of our study was that post-COVID-19 patients exhibit increased MD in the forceps minor and body of the CC. This finding suggests a potential association between microstructural brain changes in post-COVID-19 patients and reported neurological symptoms, with significant implications for research and clinical applications.

Associations between semi-quantitative evaluation of intracranial arterial calcification and total cerebral small vessel disease burden score: a retrospective case-control study.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a cause of cognitive impairment, dementia, and stroke. Developing a better understanding of the risk factor of aCSVD is key to reducing the incidence of these conditions. This study investigated the association between intracranial arterial calcification (IAC) and total cerebral small vessel disease (CSVD) burden score. This is a retrospective study, the subjects were transient ischemic attack (TIA) or acute ischemic stroke (AIS) patients. The data of 303 inpatients admitted to our study hospital between December 2018 and July 2020 were analyzed. Four imaging markers of CSVD (lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces) were evaluated by magnetic resonance imaging, and a total CSVD burden score was calculated. The experimental group was divided into four subgroups according to total CSVD burden score (1-4 points). Patients without CSVD (0 points) served as the control group. Head computerized tomography (CT) scans were used to assess ICA, using Babiarz's method. The correlations between IAC and single imaging markers of CSVD were determined using Spearman's rank correlation. Binary logic regression analysis and multivariate ordered logic regression analysis were used to determine the associations between IAC and aCSVD. IAC was positively correlated with total CSVD burden score (r = 0.681), deep white matter hyperintensities (r = 0.539), periventricular white matter hyperintensities (r = 0.570), cerebral microbleeds (r = 0.479), lacunes (r = 0.541), and enlarged perivascular spaces (r = 0.554) (all p < 0.001). After adjusting for the confounding factors of age, diabetes, and hypertension, aCSVD was independently associated with IAC grade 1-2 [odds ratio (OR) = 23.747, 95% confidence interval (CI) = 8.376-67.327] and IAC grade 3-4 (OR = 30.166, 95% CI = 8.295-109.701). aCSVD severity was independently associated with IAC grade 3-4 (OR = 4.697, 95% CI = 1.349-16.346). IAC is associated with the total CSVD burden score and single imaging signs.

Non-contrast magnetic resonance evaluation of active multiple sclerosis lesions: Emerging role of quantitative synthetic magnetic resonance imaging.

The current study aims to explore the utility of novel synthetic MRI-derived quantitative parameters including myelin-correlated volume (MyC) in identifying active MS lesions without injecting gadolinium contrast. 43 MS patients underwent institutional MS protocol including 3D FLAIR and post-contrast 3D T1VIBE sequence on a 1.5T MR Scanner in addition to synthetic MRI sequence. MS plaques were categorised into enhancing (C) and non-enhancing (N) lesions. They were also sub-categorised based on location into periventricular WM lesions (P), deep WM lesions (D), infratentorial lesions (I) and cortical-juxtacortical (C) lesions. ROIs were placed on Synthetic FLAIR images in MS lesions and quantitative parameters of R1, R2, PD and myelin-correlated volume (MyC) obtained. Sensitivity and specificity for various cut-off values to differentiate enhancing from non-enhancing multiple sclerosis lesions were calculated by performing ROC curve analysis and logistic regression analysis. Contrast enhancing lesions demonstrated significantly higher mean R1, R2 values and lower mean PD values in comparison to non-enhancing lesions (p < 0.05) but with limited specificity. Region-wise analysis revealed high AUC values for mean R1 and R2 at cortical-juxtacortical lesions (p < 0.001) followed by periventricular lesions (p < 0.003) for differentiating enhancing from non-enhancing lesions with no significant contribution from MyC and PD values. Synthetic MRI-derived quantitative parameters of mean R1, R2, MyC and PD hold value in differentiating contrast enhancing and non-enhancing MS lesions without administering gadolinium-based contrast agent. However, the current study did not achieve significant specificity for establishing the same.

Sex-related variability of white matter tracts in the whole HCP cohort

Behavioral differences between men and women have been studied extensively, as have differences in brain anatomy. However, most studies have focused on differences in gray matter, while white matter has been much less studied. We conducted a comprehensive study of 77 deep white matter tracts to analyze their volumetric and microstructural variability between men and women in the full Human Connectome Project (HCP) cohort of 1065 healthy individuals aged 22–35 years. We found a significant difference in total brain volume between men and women (+ 12.6% in men), consistent with the literature. 16 tracts showed significant volumetric differences between men and women, one of which stood out due to a larger effect size: the corpus callosum genu, which was larger in women (+ 7.3% in women, p = 5.76 × 10–19). In addition, we found several differences in microstructural parameters between men and women, both using standard Diffusion Tensor Imaging (DTI) parameters and more complex microstructural parameters from the Neurite Orientation Dispersion and Density Imaging (NODDI) model, with the tracts showing the greatest differences belonging to motor (cortico-spinal tracts, cortico-cerebellar tracts) or limbic (cingulum, fornix, thalamo-temporal radiations) systems. These microstructural differences may be related to known behavioral differences between the sexes in timed motor performance, aggressiveness/impulsivity, and social cognition.

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.

Widespread haemorrhages in infants post-shunting (WHIPS): clinical features, risk factors and neuroimaging characteristics of a rare and under-recognised phenomenon

PurposeInfants undergoing CSF shunting procedures face a rare complication which we propose to rename “Widespread Haemorrhages in Infants Post-Shunting” (WHIPS) to better capture this unique phenomenon specific to infants undergoing CSF diversion. Our objective is to analyse the risk factors for WHIPS development and provide a detailed neuroradiological description of these haemorrhages.Materials and methodsA radiology information system (RIS) was searched using the search terms “shunt” and/or “catheter” and/or “drain” and/or “ventriculoperitoneal” and/or “VP” between September 2008 to January 2021 for patients < 12 months of age. Clinical data was compiled for each patient meeting the inclusion criteria. Included cases were reviewed by three radiologists for the presence of WHIPS with calculation of the bifrontal ratio and documenting haemorrhage number, morphology, location and lobar distribution.Results51 patients met inclusion criteria, 8 WHIPS patients and 43 controls. There was a statistically significant correlation between a larger post-op head circumference and WHIPS (p = 0.04). WHIPS was associated with post-haemorrhagic hydrocephalus and post-infectious hydrocephalus (p = 0.009). WHIPS were identified in the cortico-subcortical regions, periventricular white matter, and deep white matter. Haemorrhages were either punctate, ovoid or confluent. Haemorrhages ranged from single to innumerable.ConclusionsWHIPS represent a rare and under-recognised complication of CSF shunting unique to the infantile population. We postulate deep and superficial medullary venous haemorrhage as an underlying mechanism related to disordered intracranial hydrodynamics which are exacerbated in the infantile population due to underdeveloped arachnoid granulations and a compliant skull.

Awake Craniotomy for Astrocytoma in the Left Frontal Lobe Using Augmented Reality Superimposing Tumor and White Matter Tracts: 2-Dimensional Operative Video.

Augmented reality (AR) is expected to serve as an assistive intraoperative technology in neurosurgery.1 Awake craniotomy (AC) for gliomas benefits the extent of resection, survival, and postoperative neurofunctional outcomes.2 In AC, it is critical to understand the cortical and subcortical anatomy.3 We describe the use of AR superimposing tumor and deep white matter tracts in AC. A 29-year-old right-handed woman presented to a local hospital after an episode of generalized convulsions. MRI of the head revealed a widely spreading tumor in the left middle frontal gyrus. After a left frontal craniotomy while the patient was asleep, AR was used to indicate the tumor boundary with subcortical fibers including the corticospinal tract, inferior fronto-occipital fasciculus, and cingulate fasciculus. We performed AR-assisted removal of the tumor on the surface of the middle frontal gyrus. On subcortical stimulation (SCS) of the frontal aslant tract and inferior fronto-occipital fasciculus, the patient stopped naming objects in the picture-naming test, while SCS of the left cingulate gyrus caused the patient to mistake colors in the Stroop test. The subcortical fibers identified by AR coincided with the sites of symptom elicitation by SCS. We eventually removed a large part of the tumor. Postoperative MRI confirmed 96.2% resection. The patient was discharged without any new neurological deficits. AC with AR is useful for resection of gliomas in the dominant hemisphere. The patient consented to the procedure and to the publication of her image. The ethics committee of our hospital does not require approval for case reports.

Neuropeptide FF (NPFF)-positive nerve cells of the human cerebral cortex and white matter in controls, selected neurodegenerative diseases, and schizophrenia

We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer’s disease (AD, n = 8), Pick’s disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.

Brain and cervical spinal cord MRI correlates of sensorimotor impairment in patients with multiple sclerosis.

Cervical spinal cord (cSC) lesions and atrophy contribute to disability in multiple sclerosis (MS), but associations with specific sensorimotor dysfunction require further exploration. To investigate the associations of brain and cSC magnetic resonance imaging (MRI) measures with sensorimotor impairment in MS. One hundred fifty-one MS patients and 69 healthy controls underwent 3T MRI and clinical assessments including Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT), finger tapping test (FTT), timed 25-foot walk test (T25FWT), and vibration detection threshold (VDT). Random forest ranked brain (T2-hyperintense lesion volume (T2-LV) and normalized deep gray matter (GM), cortical and white matter (WM) volumes) and cSC (T2-LV and total, GM, and WM cross-sectional areas (CSAs) at C2/C3 level) MRI measures relevance in explaining EDSS milestones (EDSS ⩾3.0, ⩾4.0, and ⩾6.0), VDT, pyramidal and sensory functional systems (P-FS and S-FS ⩾2), and motor tests impairment. Various combinations of brain and cSC MRI measures explained EDSS milestones (area under the curve (AUC) =0.879-0.900), VDT (R2 = 0.194), and impaired P-FS (AUC = 0.820), S-FS (AUC = 0.795), 9-HPT (AUC = 0.793), FTT (AUC = 0.740), and T25FWT (AUC = 0.825). cSC GM CSA was the most informative feature for all outcomes, except 9-HPT. cSC MRI measures, especially GM CSA, explain EDSS and sensorimotor dysfunction better than brain measures in MS.