Deep Gray Matter Nuclei Research Articles

Relationship of grey matter and white matter changes the visibility of perivascular space across normative lifespan

Background: Perivascular space (PVS), also known as Virchow-Robin space, has been recently recognized as one of the most important components in the glymphatic system of the brain,1 which is closely related to waste and toxins clearance in the brain. On T1- and T2-weighted images, PVS has similar signal intensities to cerebrospinal fluid (CSF), which are frequently observed in the centrum semiovale (CSO) and basal ganglia (BG) regions. A previous study2 has shown that PVS increases with age and enlarged PVS was deemed associated with neurodegenerative and vascular abnormalities in the elderly.3 Although the exact mechanism is still elusive, more evidence showed visible PVS in younger adults or even at the adolescent stage. In this study, we use the human connectome project (HCP) lifespan pilot cohort to characterize the relationship of neuronal tissue to PVS visibility across the normative lifespan.
 Methods: T1-weighted (0.8mm isotropic, TE/TR=2.12/2400 ms), T2-weighted (0.8mm isotropic, TE/TR=563/3200 ms), and diffusion magnetic resonance imaging (MRI) (1.5 mm isotropic, dir80) data were used from HCP lifespan pilot project (N=27, F/M: 12/15, age 8-75 years). PVS segmentation in white matter (WM) and BG was performed using the same method described in Sepehrband et al.4 (Figure 1). WM PVS volume fraction was calculated by dividing the total PVS volume by WM volume. Pearson correlation and one-way ANOVA were used for statistical analysis.
 Results: The grey matter (GM) volume fraction is negatively correlated with WM PVS volume (p<0.001, R2=0.374). In addition, we have observed an increase in PVS volume fraction in WM across the lifespan, but there is no significant difference in PVS volume fraction before the age of 55. From an age group range of 8-35 years old, the visible PVS is mostly located in CSO, less PVS is observed in the BG region. However, on the other hand, in the elderly group (age >65 years), high-visibility of PVS is observed both in WM and BG regions. Conclusions: Across the normative lifespan, PVS appearance is negatively correlated with the GM atrophy index, indicating the potential usage of PVS as a marker of neurodegeneration. In WM, we reported that increased PVS is associated with advancing age, which is consistent with previous reports.2 Interestingly, we found that in adolescent populations, the PVS occurs mostly in CSO but not in the BG region. In CSO, as shown from fiber orientation distribution analysis, the PVS is mainly located in crossing fiber regions with lower fiber density. However, In BG regions, the PVS occurs in deep GM nuclei (caudate, putamen) and major fiber tracts such as internal capsules or cortical spinal tracts, which are more densely packed compared to crossing-fibers in CSO. Previous studies have reported that the WM blood flow is inversely correlated with FA,5 the tightly structured fibers tend to show lower blood flow if compared to loosened ones. The high visibility of PVS in CSO may also be due to more loosened fiber structures, which lead to more axonal spaces for PVS fluid movement.

Iron deposition heterogeneity in extrapyramidal system assessed by quantitative susceptibility mapping in Parkinson's disease patients with type 2 diabetes mellitus.

PurposeExcessive brain iron depositions were found in both patients with Parkinson’s disease (PD) and those with type 2 diabetes mellitus (T2DM). The present study aimed to explore iron deposition and heterogeneity in the extrapyramidal system in PD patients with T2DM using quantitative susceptibility mapping (QSM) and further to reveal the effect of T2DM on the changes in brain iron in patients with PD.Materials and methodsA total of 38 PD patients with T2DM (PDDM), 30 PD patients without T2DM (PDND), and 20 asymptomatic control subjects (CSs) were recruited for this study. All subjects underwent multiple MRI sequences involving enhanced gradient echo T2 star weighted angiography (ESWAN). The magnetic sensitivity values (MSV) and volume of the whole nuclei (MSVW, VW) and high iron region (MSVRII, VRII) were measured on the bilateral caudate nucleus (CN), the putamen (PUT), the globus pallidus (GP), the substantia nigra (SN), the red nucleus (RN) and the dentate nucleus (DN). Clinical and laboratory data were recorded, especially for the Hoehn and Yahr (H-Y) stage, the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), the Hamilton Depression Rating Scale (HAMD), and the Hamilton Anxiety Rating Scale (HAMA). All QSM data were compared between PDDM and PDND groups and correlated with clinical and laboratory data.ResultsCompared to the PDND group, the VRII/VW of the left CN was significantly increased in the PDDM group. Significantly higher MSVW and MSVRII were also found in the PDDM group, including bilateral SN of MSVW, right PUT, and bilateral CN, GP, and SN of MSVRII. The H-Y stage of the PDDM group was significantly higher than that of the PDND group. The MSVRII of bilateral RN of the PDDM group was positively correlated with the HAMA scores. HDL, DBP, and SBP levels were associated with MSVRII of right CN in the PDDM group.ConclusionT2DM could aggravate the disease severity and anxiety in patients with PD. The iron distribution of deep gray matter nuclei in PD patients with T2DM was significantly heterogeneous, which was related to blood pressure and blood lipids.

A Preliminary Study of Alterations in Iron Disposal and Neural Activity in Ischemic Stroke.

Purpose The study aimed to evaluate the postrehabilitation changes in deep gray matter (DGM) nuclei, corticospinal tract (CST), and motor cortex area, involved in motor tasks in patients with ischemic stroke. Methods Three patients participated in this study, who had experienced an ischemic stroke on the left side of the brain. They underwent a standard rehabilitation program for four consecutive weeks, including transcranial direct current stimulation (tDCS), neuromuscular electrical stimulation (NMES), and occupational therapy. The patients' motor ability was evaluated by Fugl-Meyer assessment-upper extremity (FMA-UE) and Wolf motor function test (WMFT). Multimodal magnetic resonance imaging (MRI) was acquired from the patients by a 3 Tesla machine before and after the rehabilitation. The magnetic susceptibility changes were examined in DGM nuclei including the bilateral caudate (CA), putamen (PT), globus pallidus (GP), and thalamus (TH) using quantitative susceptibility mapping (QSM). Functional MRI (fMRI) in the motor cortex areas was acquired to evaluate the postrehab functional motor activity. The three-dimensional corticospinal tract (CST) was reconstructed using diffusion-weighted imaging (DWI) and diffusion tensor tractography (DTT), and the fractional anisotropy (FA) was measured along the tract. Ultimately, the relationship between the structural and functional changes was evaluated in CST and motor cortex. Results Postrehabilitation FMA-UE and WMFT scores increased for all patients compared to the prerehabilitation. QSM analysis revealed increasing in susceptibility values in GP and CA in all patients at the ipsilesional hemisphere. By fMRI analysis, the ipsilesional hemisphere demonstrated an increase in functional activity in motor areas for all 3 patients. In the ipsilesional hemisphere, the fractional anisotropy (FA) was increased in CST in two patients, while the mean diffusivity (MD) was decreased in CA in a patient, in PT and TH in another patient, and in PT in two patients. Conclusion This preliminary study demonstrates that the magnetic susceptibility may decrease at some ipsilesional DGM nuclei after tDCS, NMES, and occupational therapy for patients with ischemic stroke, suggesting a drop in the level of iron deposition, which may be associated with an increase in the level of activity in motor cortex after rehabilitation.

Quantitative susceptibility mapping and blood neurofilament light chain differentiate between parkinsonian disorders.

ObjectivesWe employed quantitative susceptibility mapping (QSM) to assess iron deposition in parkinsonian disorders and explored whether combining QSM values and neurofilament light (NfL) chain levels can improve the accuracy of distinguishing Parkinson’s disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).Materials and methodsForty-seven patients with PD, 28 patients with MSA, 18 patients with PSP, and 28 healthy controls (HC) were enrolled, and QSM data were reconstructed. Susceptibility values in the bilateral globus pallidus (GP), putamen (PUT), caudate nucleus (CN), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) were obtained. Plasma NfL levels of 47 PD, 18 MSA, and 14 PSP patients and 22 HC were measured by ultrasensitive Simoa technology.ResultsThe highest diagnostic accuracy distinguishing MSA from PD patients was observed with increased susceptibility values in CN (AUC: 0.740). The susceptibility values in RN yielded the highest diagnostic performance for distinguishing PSP from PD patients (AUC: 0.829). Plasma NfL levels were significantly higher in the MSA and PSP groups than in PD and HC groups. Combining the susceptibility values in the RN and plasma NfL levels improved the diagnostic performance for PSP vs. PD (AUC: 0.904), whereas plasma NfL levels had higher diagnostic accuracy for MSA vs. PD (AUC: 0.877).ConclusionThe exploratory study indicates different patterns of iron accumulation in deep gray matter nuclei in Parkinsonian disorders. Combining QSM values with NfL levels may be a promising biomarker for distinguishing PSP from PD, whereas plasma NfL may be a reliable biomarker for differentiating MSA from PD. QSM and NfL measures appeared to have low accuracy for separating PD from controls.

"Ependymal-in" Gradient of Thalamic Damage in Progressive Multiple Sclerosis.

Leptomeningeal and perivenular infiltrates are important contributors to cortical grey matter damage and disease progression in multiple sclerosis (MS). Whereas perivenular inflammation induces vasculocentric lesions, leptomeningeal involvement follows a subpial "surface-in" gradient. To determine whether similar gradient of damage occurs in deep grey matter nuclei, we examined the dorsomedial thalamic nuclei and cerebrospinal fluid (CSF) samples from 41 postmortem secondary progressive MS cases compared with 5 non-neurological controls and 12 controls with other neurological diseases. CSF/ependyma-oriented gradient of reduction in NeuN+ neuron density was present in MS thalamic lesions compared to controls, greatest (26%) in subventricular locations at the ependyma/CSF boundary and least with increasing distance (12% at 10 mm). Concomitant graded reduction in SMI31+ axon density was observed, greatest (38%) at 2 mm from the ependyma/CSF boundary and least at 10 mm (13%). Conversely, gradient of major histocompatibility complex (MHC)-II+ microglia density increased by over 50% at 2 mm at the ependyma/CSF boundary and only by 15% at 10 mm and this gradient inversely correlated with the neuronal (R=-0.91, p < 0.0001) and axonal (R=-0.79, p < 0.0001) thalamic changes. Observed gradients were also detected in normal-appearing thalamus and were associated with rapid/severe disease progression; presence of leptomeningeal tertiary lymphoid-like structures; large subependymal infiltrates, enriched in CD20+ B cells and occasionally containing CXCL13+ CD35+ follicular dendritic cells; and high CSF protein expression of a complex pattern of soluble inflammatory/neurodegeneration factors, including chitinase-3-like-1, TNFR1, parvalbumin, neurofilament-light-chains and TNF. Substantial "ependymal-in" gradient of pathological cell alterations, accompanied by presence of intrathecal inflammation, compartmentalized either in subependymal lymphoid perivascular infiltrates or in CSF, may play a key role in MS progression. SUMMARY FOR SOCIAL MEDIA: Imaging and neuropathological evidences demonstrated the unique feature of "surface-in" gradient of damage in multiple sclerosis (MS) since early pediatric stages, often associated with more severe brain atrophy and disease progression. In particular, increased inflammation in the cerebral meninges has been shown to be strictly associated with an MS-specific gradient of neuronal, astrocyte, and oligodendrocyte loss accompanied by microglial activation in subpial cortical layers, which is not directly related to demyelination. To determine whether a similar gradient of damage occurs in deep grey matter nuclei, we examined the potential neuronal and microglia alterations in the dorsomedial thalamic nuclei from postmortem secondary progressive MS cases in combination with detailed neuropathological characterization of the inflammatory features and protein profiling of paired CSF samples. We observed a substantial "subependymal-in" gradient of neuro-axonal loss and microglia activation in active thalamic lesions of progressive MS cases, in particular in the presence of increased leptomeningeal and cerebrospinal fluid (CSF) inflammation. This altered graded pathology was found associated with more severe and rapid progressive MS and increased inflammatory degree either in large perivascular subependymal infiltrates, enriched in B cells, or within the paired CSF, in particular with elevated levels of a complex pattern of soluble inflammatory and neurodegeneration factors, including chitinase 3-like-1, TNFR1, parvalbumin, neurofilament light-chains and TNF. These data support a key role for chronic, intrathecally compartmentalized inflammation in specific disease endophenotypes. CSF biomarkers, together with advance imaging tools, may therefore help to improve not only the disease diagnosis but also the early identification of specific MS subgroups that would benefit of more personalized treatments. ANN NEUROL 2022;92:670-685.

CAU-Net: A Deep Learning Method for Deep Gray Matter Nuclei Segmentation

The abnormal iron deposition of the deep gray matter nuclei is related to many neurological diseases. With the quantitative susceptibility mapping (QSM) technique, it is possible to quantitatively measure the brain iron content in vivo. To assess the magnetic susceptibility of the deep gray matter nuclei in the QSM, it is mandatory to segment the nuclei of interest first, and many automatic methods have been proposed in the literature. This study proposed a contrast attention U-Net for nuclei segmentation and evaluated its performance on two datasets acquired using different sequences with different parameters from different MRI devices. Experimental results revealed that our proposed method was superior on both datasets over other commonly adopted network structures. The impacts of training and inference strategies were also discussed, which showed that adopting test time augmentation during the inference stage can impose an obvious improvement. At the training stage, our results indicated that sufficient data augmentation, deep supervision, and nonuniform patch sampling contributed significantly to improving the segmentation accuracy, which indicated that appropriate choices of training and inference strategies were at least as important as designing more advanced network structures.

Increased Magnetic Susceptibility in the Deep Gray Matter Nuclei of Wilson's Disease: Have We Been Ignoring Atrophy?

BackgroundHistopathological studies in Wilson's disease (WD) have revealed increased copper and iron concentrations in the deep gray matter nuclei. However, the commonly used mean bulk susceptibility only reflects the regional metal concentration rather than the total metal content, and regional atrophy may affect the assessment of mean bulk susceptibility. Our study aimed to quantitatively assess the changes of metal concentration and total metal content in deep gray matter nuclei by quantitative susceptibility mapping to distinguish patients with neurological and hepatic WD from healthy controls.MethodsQuantitative susceptibility maps were obtained from 20 patients with neurological WD, 10 patients with hepatic WD, and 25 healthy controls on a 3T magnetic resonance imaging system. Mean bulk susceptibility, volumes, and total susceptibility of deep gray matter nuclei in different groups were compared using a linear regression model. The area under the curve (AUC) was calculated by receiver characteristic curve to analyze the diagnostic capability of mean bulk susceptibility and total susceptibility.ResultsMean bulk susceptibility and total susceptibility of multiple deep gray matter nuclei in patients with WD were higher than those in healthy controls. Compared with patients with hepatic WD, patients with neurological WD had higher mean bulk susceptibility but similar total susceptibility in the head of the caudate nuclei, globus pallidus, and putamen. Mean bulk susceptibility of putamen demonstrated the best diagnostic capability for patients with neurological WD, the AUC was 1, and the sensitivity and specificity were all equal to 1. Total susceptibility of pontine tegmentum was most significant for the diagnosis of patients with hepatic WD, the AUC was 0.848, and the sensitivity and specificity were 0.7 and 0.96, respectively.ConclusionBrain atrophy may affect the assessment of mean bulk susceptibility in the deep gray matter nuclei of patients with WD, and total susceptibility should be an additional metric for total metal content assessment. Mean bulk susceptibility and total susceptibility of deep gray matter nuclei may be helpful for the early diagnosis of WD.

Brain atrophy pattern in de novo Parkinson’s disease with probable RBD associated with cognitive impairment

Rapid eye movement sleep behavior disorder (RBD) is associated with high likelihood of prodromal Parkinson’s disease (PD) and is common in de novo PD. It is associated with greater cognitive impairment and brain atrophy. However, the relation between structural brain characteristics and cognition remains poorly understood. We aimed to investigate subcortical and cortical atrophy in de novo PD with probable RBD (PD-pRBD) and to relate it with cognitive impairment. We analyzed volumetry, cortical thickness, and cognitive measures from 79 PD-pRBD patients, 126 PD without probable RBD patients (PD-non pRBD), and 69 controls from the Parkinson’s Progression Markers Initiative (PPMI). Regression models of cognition were tested using magnetic resonance imaging measures as predictors. We found lower left thalamus volume in PD-pRBD compared with PD-non pRBD. Compared with controls, PD-pRBD group showed atrophy in the bilateral putamen, left hippocampus, left amygdala, and thinning in the right superior temporal gyrus. Specific deep gray matter nuclei volumes were associated with impairment in global cognition, phonemic fluency, processing speed, and visuospatial function in PD-pRBD. In conclusion, cognitive impairment and gray matter atrophy are already present in de novo PD-pRBD. Thalamus, hippocampus, and putamen volumes were mainly associated with these cognitive deficits.

Automatic detection of neuromelanin and iron in the midbrain nuclei using a magnetic resonance imaging-based brain template.

Parkinson disease (PD) is a chronic progressive neurodegenerative disorder characterized pathologically by early loss of neuromelanin (NM) in the substantia nigra pars compacta (SNpc) and increased iron deposition in the substantia nigra (SN). Degeneration of the SN presents as a 50 to 70% loss of pigmented neurons in the ventral lateral tier of the SNpc at the onset of symptoms. Also, using magnetic resonance imaging (MRI), iron deposition and volume changes of the red nucleus (RN), and subthalamic nucleus (STN) have been reported to be associated with disease status and rate of progression. Further, the STN serves as an important target for deep brain stimulation treatment in advanced PD patients. Therefore, an accurate in‐vivo delineation of the SN, its subregions and other midbrain structures such as the RN and STN could be useful to better study iron and NM changes in PD. Our goal was to use an MRI template to create an automatic midbrain deep gray matter nuclei segmentation approach based on iron and NM contrast derived from a single, multiecho magnetization transfer contrast gradient echo (MTC‐GRE) imaging sequence. The short echo TE = 7.5 ms data from a 3D MTC‐GRE sequence was used to find the NM‐rich region, while the second echo TE = 15 ms was used to calculate the quantitative susceptibility map for 87 healthy subjects (mean age ± SD: 63.4 ± 6.2 years old, range: 45–81 years). From these data, we created both NM and iron templates and calculated the boundaries of each midbrain nucleus in template space, mapped these boundaries back to the original space and then fine‐tuned the boundaries in the original space using a dynamic programming algorithm to match the details of each individual's NM and iron features. A dual mapping approach was used to improve the performance of the morphological mapping of the midbrain of any given individual to the template space. A threshold approach was used in the NM‐rich region and susceptibility maps to optimize the DICE similarity coefficients and the volume ratios. The results for the NM of the SN as well as the iron containing SN, STN, and RN all indicate a strong agreement with manually drawn structures. The DICE similarity coefficients and volume ratios for these structures were 0.85, 0.87, 0.75, and 0.92 and 0.93, 0.95, 0.89, 1.05, respectively, before applying any threshold on the data. Using this fully automatic template‐based deep gray matter mapping approach, it is possible to accurately measure the tissue properties such as volumes, iron content, and NM content of the midbrain nuclei.

Are Neurophysiological Biomarkers Able to Discriminate Multiple Sclerosis Clinical Subtypes?

Secondary progressive multiple sclerosis (SPMS) subtype is retrospectively diagnosed, and biomarkers of the SPMS are not available. We aimed to identify possible neurophysiological markers exploring grey matter structures that could be used in clinical practice to better identify SPMS. Fifty-five people with MS and 31 healthy controls underwent a transcranial magnetic stimulation protocol to test intracortical interneuron excitability in the primary motor cortex and somatosensory temporal discrimination threshold (STDT) to test sensory function encoded in cortical and deep grey matter nuclei. A logistic regression model was used to identify a combined neurophysiological index associated with the SP subtype. We observed that short intracortical inhibition (SICI) and STDT were the only variables that differentiated the RR from the SP subtype. The logistic regression model provided a formula to compute the probability of a subject being assigned to an SP subtype based on age and combined SICI and STDT values. While only STDT correlated with disability level at baseline evaluation, both SICI and STDT were associated with disability at follow-up. SICI and STDT abnormalities reflect age-dependent grey matter neurodegenerative processes that likely play a role in SPMS pathophysiology and may represent easily accessible neurophysiological biomarkers for the SPMS subtype.

Brain iron deposition and movement disorders in hereditary haemochromatosis without liver failure: A cross-sectional study.

Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. This is a cross-sectional study. Consecutive subjects with HFE-haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age- and sex-matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping-based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. Fifty-two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty-five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH.

Magnetic susceptibility anisotropy in normal appearing white matter in multiple sclerosis from single-orientation acquisition

Quantitative susceptibility mapping (QSM) has been successfully applied to study changes in deep grey matter nuclei as well as in lesional tissue, but its application to white matter has been complicated by the observed orientation dependence of gradient echo signal. The anisotropic susceptibility tensor is thought to be at the origin of this orientation dependence, and magnetic susceptibility anisotropy (MSA) derived from this tensor has been proposed as a marker of the state and integrity of the myelin sheath and may therefore be of particular interest for the study of demyelinating pathologies such as multiple sclerosis (MS). Reconstruction of the susceptibility tensor, however, requires repeated measurements with multiple head orientations, rendering the approach impractical for clinical applications.In this study, we combined single-orientation QSM with fibre orientation information to assess apparent MSA in three white matter tracts, i.e., optic radiation (OR), splenium of the corpus callosum (SCC), and superior longitudinal fascicle (SLF), in two cohorts of 64 healthy controls and 89 MS patients. The apparent MSA showed a significant decrease in optic radiation in the MS cohort compared with healthy controls. It decreased in the MS cohort with increasing lesion load in OR and with disease duration in the splenium. All of this suggests demyelination in normal appearing white matter. However, the apparent MSA observed in the SLF pointed to potential systematic issues that require further exploration to realize the full potential of the presented approach. Despite the limitations of such single-orientation ROI-specific estimation, we believe that our clinically feasible approach to study degenerative changes in WM is worthy of further investigation.

Substantia nigra iron affects functional connectivity networks modifying working memory performance in younger adults.

Brain iron affects working memory (WM) but the impact of iron content in deep grey matter nuclei on WM networks is unknown. We aimed to test whether deep grey matter nuclei iron concentration can affect resting-state functional connectivity (rsFC) within brain networks modifying WM performance. An N-back WM paradigm was applied in a hundred healthy younger adults. The participants then underwent a resting-state functional magnetic resonance imaging (fMRI) for brain network analysis and quantitative susceptibility mapping (QSM) imaging for assessment of deep grey matter nuclei iron concentration. Higher substantia nigra (SN) iron concentration was associated with lower rsFC between SN and brain regions of the temporal/frontal lobe but with better WM performance after controlling for age, gender and education. A follow-up mediation analysis also indicated that functional connectivity may mediate the link between SN iron and WM performance. Our results suggest that high SN iron concentration may affect communication between the SN and temporal/frontal lobe and is associated with strengthened WM performance in younger adults.

Human viral encephalitis associated with suid herpesvirus 1.

BackgroundSuid herpesvirus type 1 (SHV1) is a type of neurotropic virus able to infect various species. However, the clinical cases of human SHV1 encephalitis are still rarely reported, and the clinical characteristics, treatment, and prognosis of human SHV1 encephalitis are still unclear.MethodsIn this study, we reported 2 cases of human encephalitis associated with SHV1 infection and reviewed the other 18 cases from the literatures. A total of 20 cases with human SHV1 encephalitis were summarized and re-analyzed.ResultsNineteen of 20 patients had a history of swine-related occupational exposure before illness onset. All patients initially presented with influenza-like symptoms and then developed seizures, disturbed consciousness, and endophthalmitis. All patients with clinical outcome of modified Rankin Scale of 5 or 6 suffered from rapid progressive respiratory failure. The results of cerebrospinal fluid (CSF) indicated aseptic or viral infection. MRI findings of SHV1 encephalitis were prone to distribute in temporal-frontal and insular cortex, which was similar to the pattern of herpes simplex virus encephalitis, while some cases with involvements of gray matter nuclei had a high rate of mortality. Metagenomic next-generation sequencing (mNGS) revealed that all patients had unique SHV1 sequences with variable reads in the CSF.ConclusionsThe variant SHV1 can cause a new type of human viral encephalitis, characterized by acute, fulminating, and catastrophic central nervous system infection. Rapid progressive respiratory failure and extensive lesions of deep gray matter nuclei might be indicators to poor prognosis. No approved treatments for the encephalitis are available, but it is possible to diagnose encephalitis quickly by mNGS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10072-021-05633-0.

Quantitative susceptibility mapping to evaluate brain iron deposition and its correlation with physiological parameters in hypertensive patients.

BackgroundRegional excessive iron overload is pernicious to motor functions and cognitive functioning of the brain. The aim of this research was to utilize quantitative susceptibility mapping (QSM) to inspect brain iron accumulation in patients with hypertension (HP), and to evaluate whether it is correlated with physiological parameters.MethodsThirty-one HP and 31 age- and sex-matched healthy controls (HC) were included. All participants underwent brain magnetic resonance imaging (MRI), and QSM data were obtained. Differences in brain iron deposition in deep gray matter nuclei of participants were compared between HP and HC. The correlations between iron deposition, body mass index (BMI), maximum systolic blood pressure (SBP), and diastolic blood pressure (DBP) were analyzed.ResultsThe HP group showed increased susceptibility values in the caudate nucleus (CA), putamen (PU), globus pallidus (GP), and dorsal thalamus (TH), compared with the HC group. There was a significant positive correlation between BMI and the susceptibility values in the dentate nucleus (DN); the maximum SBP and DBP were positively correlated with magnetic susceptibility of the CA, PU, GP, and TH, respectively.ConclusionsThese results are indicative of the role of overload brain iron in deep brain gray matter nuclei in HP and suggest that HP is associated with excess brain iron in certain deep gray matter regions.

The Effect of Deep Learning-Based QSM Magnetic Resonance Imaging on the Subthalamic Nucleus.

In order to study the influence of quantitative magnetic susceptibility mapping (QSM) on them. A 2.5D Attention U-Net Network based on multiple input and multiple output, a method for segmenting RN, SN, and STN regions in high-resolution QSM images is proposed, and deep learning realizes accurate segmentation of deep nuclei in brain QSM images. Experimental results show data first cuts each layer of 0 100 case data, based on the image center, from 384 × 288 to the size of 128 × 128. Image combination: each layer of the image in the layer direction combines with two adjacent images into a 2.5D image, i.e., (It − m It; It + i), where It represents the layer i image. At this time, the size of the image changes from 128 × 128 to 128 × 128 × 3, in which 3 represents three consecutive layers of images. The SNR of SWP I to STN is twice that of SWI. The small deep gray matter nuclei (RN, SN, and STN) in QSM images of the brain and the pancreas with irregular shape and large individual differences in abdominal CT images can be automatically segmented.

Neurochemical Features of Rem Sleep Behaviour Disorder.

Dopaminergic deficiency, shown by many studies using functional neuroimaging with Single Photon Emission Computerized Tomography (SPECT) and Positron Emission Tomography (PET), is the most consistent neurochemical feature of rapid eye movement (REM) sleep behaviour disorder (RBD) and, together with transcranial ultrasonography, and determination of alpha-synuclein in certain tissues, should be considered as a reliable marker for the phenoconversion of idiopathic RBD (iRBD) to a synucleopathy (Parkinson’s disease –PD- or Lewy body dementia -LBD). The possible role in the pathogenesis of RBD of other neurotransmitters such as noradrenaline, acetylcholine, and excitatory and inhibitory neurotransmitters; hormones such as melatonin, and proinflammatory factors have also been suggested by recent reports. In general, brain perfusion and brain glucose metabolism studies have shown patterns resembling partially those of PD and LBD. Finally, the results of structural and functional MRI suggest the presence of structural changes in deep gray matter nuclei, cortical gray matter atrophy, and alterations in the functional connectivity within the basal ganglia, the cortico-striatal, and the cortico-cortical networks, but they should be considered as preliminary.

Magnetic resonance imaging and spectroscopy in evaluation of hypoxic ischemic encephalopathy in pediatric age group

BackgroundHypoxic ischemic encephalopathy is a major cause of pediatric mortality and morbidity, with possible long-term neurologic sequel, such as cerebral palsy. With improvements in care of at-risk neonates, more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. The aim of the study was to assess the additive role of magnetic resonance spectroscopy over conventional MRI in diagnosis and early prediction of pathological motor development in neonates with hypoxic ischemic encephalopathy.ResultsMRS ratios showed significant difference between unfavorable and normal outcome infants. MRS ratios as Lac/Cr, NAA/Cr and NAA/Cho within basal ganglia, thalamus and white matter can significantly differentiate between patients with normal and pathological outcome at 1 year.Lac/Cr positively correlates with the severity of HIE. Both NAA/Cr and NAA/Cho negatively correlate with the severity of the disease. Ratios cutoff values as Lac/Cr above 0.38 and 0.42 in basal ganglia and white matter, respectively, NAA/Cr below 0.9 and 0.8 in basal ganglia and occipital white matter, respectively, and NAA/Cho below 0.29 and 0.31 in basal ganglia and frontal white matter, respectively, were significantly predictive of pathological outcome.ConclusionHigh Lac/Cr, low NAA/Cr and low NAA/Cho ratios within examined regions of the brain including deep grey matter nuclei as well as white matter are associated with an adverse outcome in infants with perinatal asphyxia. MRS is an accurate quantitative MR biomarker within the neonatal period for prediction of neurodevelopmental outcome after perinatal HIE. MRS may be useful in early clinical management decisions, and counseling parents thereby ensuring appropriate early intervention and rehabilitation.

Motor and higher-order functions topography of the human dentate nuclei identified with tractography and clustering methods.

Deep gray matter nuclei are the synaptic relays, responsible to route signals between specific brain areas. Dentate nuclei (DNs) represent the main output channel of the cerebellum and yet are often unexplored especially in humans. We developed a multimodal MRI approach to identify DNs topography on the basis of their connectivity as well as their microstructural features. Based on results, we defined DN parcellations deputed to motor and to higher‐order functions in humans in vivo. Whole‐brain probabilistic tractography was performed on 25 healthy subjects from the Human Connectome Project to infer DN parcellations based on their connectivity with either the cerebral or the cerebellar cortex, in turn. A third DN atlas was created inputting microstructural diffusion‐derived metrics in an unsupervised fuzzy c‐means classification algorithm. All analyses were performed in native space, with probability atlas maps generated in standard space. Cerebellar lobule‐specific connectivity identified one motor parcellation, accounting for about 30% of the DN volume, and two non‐motor parcellations, one cognitive and one sensory, which occupied the remaining volume. The other two approaches provided overlapping results in terms of geometrical distribution with those identified with cerebellar lobule‐specific connectivity, although with some differences in volumes. A gender effect was observed with respect to motor areas and higher‐order function representations. This is the first study that indicates that more than half of the DN volumes is involved in non‐motor functions and that connectivity‐based and microstructure‐based atlases provide complementary information. These results represent a step‐ahead for the interpretation of pathological conditions involving cerebro‐cerebellar circuits.

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy

ObjectiveMalformations of cortical development (MCD), including focal cortical dysplasia (FCD), are the most common cause of drug-resistant focal epilepsy in children. Histopathological lesion characterisation demonstrates abnormal cell types and lamination, alterations in myelin (typically co-localised with iron), and sometimes calcification. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility (χ) reflecting it's mineral composition.We used QSM to investigate abnormal tissue composition in a group of children with focal epilepsy with comparison to effective transverse relaxation rate (R2*) and Synchrotron radiation X-ray fluorescence (SRXRF) elemental maps. Our primary hypothesis was that reductions in χ would be found in FCD lesions, resulting from alterations in their iron and calcium content. We also evaluated deep grey matter nuclei for changes in χ with age. MethodsQSM and R2* maps were calculated for 40 paediatric patients with suspected MCD (18 histologically confirmed) and 17 age-matched controls.Patients’ sub-groups were defined based on concordant electro-clinical or histopathology data. Quantitative investigation of QSM and R2* was performed within lesions, using a surface-based approach with comparison to homologous regions, and within deep brain regions using a voxel-based approach with regional values modelled with age and epilepsy as covariates.Synchrotron radiation X-ray fluorescence (SRXRF) was performed on brain tissue resected from 4 patients to map changes in iron, calcium and zinc and relate them to MRI parameters. ResultsCompared to fluid‐attenuated inversion recovery (FLAIR) or T1‐weighted imaging, QSM improved lesion conspicuity in 5% of patients.In patients with well-localised lesions, quantitative profiling demonstrated decreased χ, but not R2*, across cortical depth with respect to the homologous regions. Contra-lateral homologous regions additionally exhibited increased χ at 2–3 mm cortical depth that was absent in lesions. The iron decrease measured by the SRXRF in FCDIIb lesions was in agreement with myelin reduction observed by Luxol Fast Blue histochemical staining.SRXRF analysis in two FCDIIb tissue samples showed increased zinc and calcium in one patient, and decreased iron in the brain region exhibiting low χ and high R2* in both patients. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus. ConclusionQSM non-invasively revealed cortical/sub-cortical tissue alterations in MCD lesions and in particular that χ changes in FCDIIb lesions were consistent with reduced iron, co-localised with low myelin and increased calcium and zinc content. These findings suggest that measurements of cortical χ could be used to characterise tissue properties non-invasively in epilepsy lesions.