Deep Gray Matter Research Articles

Cerebral Microbleeds Are Associated with Widespread Blood-Brain Barrier Leakage

Introduction: The pathogenesis of cerebral microbleeds (CMBs) is incompletely understood, but blood-brain barrier (BBB) leakage may play a key role. This study aimed to investigate the relationship between compromised BBB integrity and CMBs as well as cognitive function. Methods: Ninety-seven participants were enrolled in this cross-sectional study, involving 24 CMB patients. Dynamic contrast-enhanced-magnetic resonance imaging was used to measure BBB permeability, and cognitive function was assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Results: Compared with participants without CMBs, CMB patients had higher volume transfer constant (Ktrans, all p < 0.01) and area under the concentration curve (AUC, all p < 0.05) in normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter (DGM). Multivariable linear regression analyses revealed that CMB patients had significantly higher Ktrans in NAWM and AUC in NAWM, WMH, and CGM after adjustment for age, sex, vascular risk factors, and cognitive scores. MMSE and MoCA scores decreased with increasing Ktrans in WMH and DGM as well as AUC in WMH after adjustment for age, sex, CMB group, and education length. Conclusion: This study demonstrated that widespread BBB leakage was prevalent in CMB patients, suggesting that compromised BBB integrity may play a key role in the pathogenesis of CMBs and could lead to cognitive impairment.

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6–8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks’ gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks’ gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

Spatiotemporal patterns of brain iron-oxygen metabolism in patients with Parkinson's disease.

Iron deposition and mitochondrial dysfunction are closely associated with the genesis and progression of Parkinson's disease (PD). This study aims to extract susceptibility and oxygen extraction fraction (OEF) values of deep grey matter (DGM) to explore spatiotemporal progression patterns of brain iron-oxygen metabolism in PD. Ninety-five PD patients and forty healthy controls (HCs) were included. Quantitative susceptibility mapping (QSM) and OEF maps were computed from MRI multi-echo gradient echo data. Analysis of covariance (ANCOVA) was used to compare mean susceptibility and OEF values in DGM between early-stage PD (ESP), advanced-stage PD (ASP) patients and HCs. Then Granger causality analysis on the pseudo-time-series of MRI data was applied to assess the causal effect of early altered nuclei on iron content and oxygen extraction in other DGM nuclei. The susceptibility values in substantia nigra (SN), red nucleus, and globus pallidus (GP) significantly increased in PD patients compared with HCs, while the iron content in GP did not elevate obviously until the late stage. The mean OEF values for the caudate nucleus, putamen, and dentate nucleus were higher in ESP patients than in ASP patients or/and HCs. We also found that iron accumulation progressively expands from the midbrain to the striatum. These alterations were correlated with clinical features and improved AUC for early PD diagnosis to 0.824. Abnormal cerebral iron deposition and tissue oxygen utilization in PD measured by QSM and OEF maps could reflect pathological alterations in neurodegenerative processes and provide valuable indicators for disease identification and management. Noninvasive assessment of cerebral iron-oxygen metabolism may serve as clinical evidence of pathological changes in PD and improve the validity of diagnosis and disease monitoring. • Quantitative susceptibility mapping and oxygen extraction fraction maps indicated the cerebral pathology of abnormal iron accumulation and oxygen metabolism in Parkinson's disease. • Iron deposition is mainly in the midbrain, while altered oxygen metabolism is concentrated in the striatum and cerebellum. • The susceptibility and oxygen extraction fraction values in subcortical nuclei were associated with clinical severity.

Total and Regional Brain Volumes in Fetuses With Congenital Heart Disease.

Congenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear. To utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes. Retrospective case-control study. Three hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery. T2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner. Images were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups. ANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR-values <0.05 were considered statistically significant. Total and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios. Total and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal. 3 TECHNICAL EFFICACY: Stage 3.

Multimodal Investigation of Deep Gray Matter Nucleus in Patients with Multiple Sclerosis and Their Clinical Correlations: A Multivariate Pattern Analysis Study.

Deep gray matter (DGM) nucleus are involved in patients with multiple sclerosis (MS) and are strongly associated with clinical symptoms. We used machine learning approach to further explore microstructural alterations in DGM of MS patients. One hundred and fifteen MS patients and seventy-one healthy controls (HC) underwent brain MRI. The fractional anisotropy (FA), mean diffusivity (MD), quantitative susceptibility value (QSV) and volumes of the caudate nucleus (CN), putamen (PT), globus pallidus (GP), and thalamus (TH) were measured. Multivariate pattern analysis, based on a machine-learning algorithm, was applied to investigate the most damaged regions. Partial correlation analysis was used to investigate the correlation between MRI quantitative metrics and clinical neurological scores. The area under the curve of FA-based classification model was 0.83, while they were 0.93 for MD and 0.81 for QSV. The Montreal cognitive assessment scores were correlated with the volume of the DGM and the expanded disability status scale scores were correlated with the MD of the GP and PT. The study results indicated that MS patients had involvement of DGM with the CN being the most affected. The atrophy of DGM in MS patients mainly affected cognitive function and the microstructural damage of DGM was mainly correlated with clinical disability.

Volumetric magnetic resonance imaging differences between complex febrile seizure and recurrent simple febrile seizure

PurposeWe investigated the volumetric differences in cortical and subcortical structures between patients with complex febrile seizure (FS) and recurrent simple FS. We aimed to identify the brain morphological patterns of children with complex FS. MethodsTwenty-five patients with complex FS and age- and sex-matched 25 patients with recurrent simple FS with structural magnetic resonance imaging (MRI) scans were studied. Cortical volumetric analysis was performed using a voxel-based morphometry method with the CAT12 toolbox within SPM12. FSL-FIRST was used to obtain volume measures of subcortical deep grey matter structures (amygdala, caudate nucleus, thalamus, nucleus accumbens, putamen, globus pallidus, and hippocampus). The volumetric asymmetry index (AI) and laterality index (LI) were calculated for each subcortical structure. ResultsCompared with recurrent simple FS, complex FS demonstrated lower volume in the left putamen (p = .003) and right nucleus accumbens (p = .001). Additionally, patients with complex FS presented a higher magnitude of AI of the nucleus accumbens (p < .001) compared with recurrent simple FS. ConclusionsThe findings indicate that volumetric analysis may be a useful marker for the detection of FS-induced changes that reflect microstructural alterations. This study is the first to report on alterations in the putamen and nucleus accumbens in FS.

Functional reorganization of intranetwork and internetwork connectivity in patients with Ménière’s disease

Ménière’s disease (MD) is associated with functional reorganization not only in the auditory or sensory cortex but also in other control and cognitive areas. In this study, we examined intranetwork and internetwork connectivity differences between 55 MD patients and 70 healthy controls (HC) in 9 well-defined resting-state networks. Functional connectivity degree was lower in MD compared to HC in 19 brain areas involved in the somatomotor, auditory, ventral attention, default mode, limbic, and deep gray matter networks. In addition, we observed lower intranetwork connectivity in the auditory, ventral attention, and limbic networks, as well as lower internetwork connectivity between the somatomotor and limbic networks, and between the auditory and somatomotor, deep gray matter, and ventral attention networks, and between the deep gray matter and default mode network. Furthermore, we identified 81 pairs of brain areas with significant differences in functional connectivity between MD patients and HC at the edge level. Notably, the left amygdala’s functional connectivity degree was positively correlated with MD’s disease stage, and the ventral attention network’s intranetwork connectivity was positively correlated with the healthy side vestibular ratio. Our findings suggest that these functional network reorganization alterations may serve as potential biomarkers for predicting clinical progression, evaluating disease severity, and gaining a better understanding of MD’s pathophysiology. Large-scale network studies using neuroimaging techniques can provide additional insights into the underlying mechanisms of MD.

Quantitative susceptibility mapping of brain iron in healthy aging and cognition

Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique that can assess the magnetic properties of cerebral iron in vivo. Although brain iron is necessary for basic neurobiological functions, excess iron content disrupts homeostasis, leads to oxidative stress, and ultimately contributes to neurodegenerative disease. However, some degree of elevated brain iron is present even among healthy older adults. To better understand the topographical pattern of iron accumulation and its relation to cognitive aging, we conducted an integrative review of 47 QSM studies of healthy aging, with a focus on five distinct themes. The first two themes focused on age-related increases in iron accumulation in deep gray matter nuclei versus the cortex. The overall level of iron is higher in deep gray matter nuclei than in cortical regions. Deep gray matter nuclei vary with regard to age-related effects, which are most prominent in the putamen, and age-related deposition of iron is also observed in frontal, temporal, and parietal cortical regions during healthy aging. The third theme focused on the behavioral relevance of iron content and indicated that higher iron in both deep gray matter and cortical regions was related to decline in fluid (speed-dependent) cognition. A handful of multimodal studies, reviewed in the fourth theme, suggest that iron interacts with imaging measures of brain function, white matter degradation, and the accumulation of neuropathologies. The final theme concerning modifiers of brain iron pointed to potential roles of cardiovascular, dietary, and genetic factors. Although QSM is a relatively recent tool for assessing cerebral iron accumulation, it has significant promise for contributing new insights into healthy neurocognitive aging.

The clinical value of deep gray matter 3T MRI perfusion in patients with multiple sclerosis

Background. Multiple sclerosis (MS) is a common neurological disorder between adults. Magnetic resonance imaging (MRI) is the imaging modality of choice, new MRI techniques helped in more accurate assessment of the disease extent, activity and severity. In dynamic susceptibility contrast (DSC), the perfusion of the lesions as well as normally appearing white and gray matter of the brain have been assessed. Objective. To highlight the role of MRI perfusion of the deep gray matter in multiple sclerosis patients and its relation to their clinical disability and cognitive impairment Methods. 40 patients with MS were enrolled in this study, they were divided into two groups (group A with mild clinical disease and preserved cognitive functions, and group B with marked clinical disease and cognitive functions impairment) they were divided according to their clinical disability and cognitive impairment assessed by experienced neurologist, Additional 20 healthy controls were included. Perfusion parameters including cerebral blood volume(CBV), cerebral blood flow (CBF) and mean transit time (MTT) of the deep gray matter were compared for healthy controls and for the study groups. Results. The perfusion values of the thalamus, putamen and caudate were significantly changed in group B that shows marked decrease in CBV and CBF and increased MTT compared with group A and the controls, With respect to group (A), there was no significant difference between the patients and controls Conclusion. The decrease of perfusion of the deep gray matter in patients with MS is associated with the severity of the disease and cognitive impairment.

Evaluation of whole-brain oxygen metabolism in Alzheimer's disease using QSM and quantitative BOLD

ObjectiveThe objective of this study was to evaluate the whole-brain pattern of oxygen extraction fraction (OEF), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) perturbation in Alzheimer's disease (AD) and investigate the relationship between regional cerebral oxygen metabolism and global cognition. MethodsTwenty-six AD patients and 25 age-matched healthy controls (HC) were prospectively recruited in this study. Mini-Mental State Examination (MMSE) was used to evaluate cognitive status. We applied the QQ-CCTV algorithm which combines quantitative susceptibility mapping and quantitative blood oxygen level-dependent models (QQ) for OEF calculation. CBF map was computed from arterial spin labeling and CMRO2 was generated based on Fick's principle. Whole-brain and regional OEF, CBF, and CMRO2 analyses were performed. The associations between these measures in substructures of deep brain gray matter and MMSE scores were assessed. ResultsWhole brain voxel-wise analysis showed that CBF and CMRO2 values significantly decreased in AD predominantly in the bilateral angular gyrus, precuneus gyrus and parieto-temporal regions. Regional analysis showed that CBF value decreased in the bilateral caudal hippocampus and left rostral hippocampus and CMRO2 value decreased in left caudal and rostral hippocampus in AD patients. Considering all subjects in the AD and HC groups combined, the mean CBF and CMRO2 values in the bilateral hippocampus positively correlated with the MMSE score. ConclusionCMRO2 mapping with the QQ-CCTV method - which is readily available in MR systems for clinical practice - can be a potential biomarker for AD. In addition, CMRO2 in the hippocampus may be a useful tool for monitoring cognitive impairment.

Sub-voxel quantitative susceptibility mapping for assessing whole-brain magnetic susceptibility from ages 4 to 80.

The evolution of magnetic susceptibility of the brain is mainly determined by myelin in white matter (WM) and iron deposition in deep gray matter (DGM). However, existing imaging techniques have limited abilities to simultaneously quantify the myelination and iron deposition within a voxel throughout brain development and aging. For instance, the temporal trajectories of iron in the brain WM and myelination in DGM have not been investigated during the aging process. This study aimed to map the age-related iron and myelin changes in the whole brain, encompassing myelin in DGM and iron deposition in WM, using a novel sub-voxel quantitative susceptibility mapping (QSM) method. To achieve this, a cohort of 494 healthy adults (18-80 years old) was studied. The sub-voxel QSM method was employed to obtain the paramagnetic and diamagnetic susceptibility based on the approximated map from acquired map. The linear relationship between and maps was established from the regression coefficients on a small cohort data acquired with both 3D gradient recalled echo data and mapping. Large cohort sub-voxel susceptibility maps were used to create longitudinal and age-specific atlases via group-wise registration. To explore the differential developmental trajectories in the DGM and WM, we employed nonlinear models including exponential and Poisson functions, along with generalized additive models. The constructed atlases reveal the iron accumulation in the posterior part of the putamen and the gradual myelination process in the globus pallidus with aging. Interestingly, the developmental trajectories show that the rate of myelination differs among various DGM regions. Furthermore, the process of myelin synthesis is paralleled by an associated pattern of iron accumulation in the primary WM fiber bundles. In summary, our study offers significant insights into the distinctive developmental trajectories of iron in the brain's WM and myelination/demyelination in the DGM in vivo. These findings highlight the potential of using sub-voxel QSM to uncover new perspectives in neuroscience and improve our understanding of whole-brain myelination and iron deposit processes across the lifespan.

Multimodal MRI study on the relation between WM integrity and connected GM atrophy and its effect on disability in early multiple sclerosis

BackgroundMultiple sclerosis (MS) is characterized by pathology in white matter (WM) and atrophy of grey matter (GM), but it remains unclear how these processes are related, or how they influence clinical progression.ObjectiveTo study the spatial and temporal relationship between GM atrophy and damage in connected WM in relapsing–remitting (RR) MS in relation to clinical progression.MethodsHealthy control (HC) and early RRMS subjects visited our center twice with a 1-year interval for MRI and clinical examinations, including the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores. RRMS subjects were categorized as MSFC decliners or non-decliners based on ΔMSFC over time. Ten deep (D)GM and 62 cortical (C) GM structures were segmented and probabilistic tractography was performed to identify the connected WM. WM integrity was determined per tract with, amongst others, fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), and myelin water fraction (MWF). Linear mixed models (LMMs) were used to investigate GM and WM differences between HC and RRMS, and between MSFC decliners and non-decliners. LMM was also used to test associations between baseline WM z-scores and changes in connected GM z-scores, and between baseline GM z-scores and changes in connected WM z-scores, in HC/RRMS subjects and in MSFC decliners/non-decliners.ResultsWe included 13 HCs and 31 RRMS subjects with an average disease duration of 3.5 years and a median EDSS of 3.0. Fifteen RRMS subjects showed declining MSFC scores over time, and they showed higher atrophy rates and greater WM integrity loss compared to non-decliners. Lower baseline WM integrity was associated with increased CGM atrophy over time in RRMS, but not in HC subjects. This effect was only seen in MSFC decliners, especially when an extended WM z-score was used, which included FA, MD, NDI and MWF. Baseline GM measures were not significantly related to WM integrity changes over time in any of the groups.DiscussionLower baseline WM integrity was related to more cortical atrophy in RRMS subjects that showed clinical progression over a 1-year follow-up, while baseline GM did not affect WM integrity changes over time. WM damage, therefore, seems to drive atrophy more than conversely.

MR imaging and outcome in neonatal HIBD models are correlated with sex: the value of diffusion tensor MR imaging and diffusion kurtosis MR imaging.

Hypoxic-ischemic encephalopathy can lead to lifelong morbidity and premature death in full-term newborns. Here, we aimed to determine the efficacy of diffusion kurtosis (DK) [mean kurtosis (MK)] and diffusion tensor (DT) [fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD)] parameters for the early diagnosis of early brain histopathological changes and the prediction of neurodegenerative events in a full-term neonatal hypoxic-ischemic brain injury (HIBD) rat model. The HIBD model was generated in postnatal day 7 Sprague-Dawley rats to assess the changes in DK and DT parameters in 10 specific brain structural regions involving the gray matter, white matter, and limbic system during acute (12 h) and subacute (3 d and 5 d) phases after hypoxic ischemia (HI), which were validated against histology. Sensory and cognitive parameters were assessed by the open field, novel object recognition, elevated plus maze, and CatWalk tests. Repeated-measures ANOVA revealed that specific brain structures showed similar trends to the lesion, and the temporal pattern of MK was substantially more varied than DT parameters, particularly in the deep gray matter. The change rate of MK in the acute phase (12 h) was significantly higher than that of DT parameters. We noted a delayed pseudo-normalization for MK. Additionally, MD, AD, and RD showed more pronounced differences between males and females after HI compared to MK, which was confirmed in behavioral tests. HI females exhibited anxiolytic hyperactivity-like baseline behavior, while the memory ability of HI males was affected in the novel object recognition test. CatWalk assessments revealed chronic deficits in limb gait parameters, particularly the left front paw and right hind paw, as well as poorer performance in HI males than HI females. Our results suggested that DK and DT parameters were complementary in the immature brain and provided great value in assessing early tissue microstructural changes and predicting long-term neurobehavioral deficits, highlighting their ability to detect both acute and long-term changes. Thus, the various diffusion coefficient parameters estimated by the DKI model are powerful tools for early HIBD diagnosis and prognosis assessment, thus providing an experimental and theoretical basis for clinical treatment.

Dynamic contrast-enhanced MRI shows altered blood–brain barrier function of deep gray matter structures in neuroborreliosis: a case–control study

BackgroundMain aim was assessment of regional blood–brain barrier (BBB) function by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with neuroborreliosis. Secondary aim was to study the correlation of BBB function with biochemical, clinical, and cognitive parameters.MethodsRegional ethical committee approved this prospective single-center case–control study. Within 1 month after diagnosis of neuroborreliosis, 55 patients underwent DCE-MRI. The patient group consisted of 25 males and 30 females with mean age 58 years, and the controls were 8 males and 7 females with mean age 57 years. Pharmacokinetic compartment modelling with Patlak fit was applied, providing estimates for capillary leakage rate and blood volume fraction. Nine anatomical brain regions were sampled with auto-generated binary masks. Fatigue, severity of clinical symptoms and findings, and cognitive function were assessed in the acute phase and 6 months after treatment.ResultsLeakage rates and blood volume fractions were lower in patients compared to controls in the thalamus (p = 0.027 and p = 0.018, respectively), caudate nucleus (p = 0.009 for both), and hippocampus (p = 0.054 and p = 0.009). No correlation of leakage rates with fatigue, clinical disease severity or cognitive function was found.ConclusionsIn neuroborreliosis, leakage rate and blood volume fraction in the thalamus, caudate nucleus, and hippocampus were lower in patients compared to controls. DCE-MRI provided new insight to pathophysiology of neuroborreliosis, and can serve as biomarker of BBB function and regulatory mechanisms of the neurovascular unit in infection and inflammation.Relevance statementDCE-MRI provided new insight to pathophysiology of neuroborreliosis, and can serve as biomarker of blood–brain barrier function and regulatory mechanisms of the neurovascular unit in infection and inflammation.Key points• Neuroborreliosis is an infection with disturbed BBB function.• Microvessel leakage can be studied with DCE-MRI.• Prospective case–control study showed altered microvessel properties in thalamus, caudate, and hippocampus.Graphical

The effects of normobaric and hyperbaric oxygenation on MRI signal intensities in T1 -weighted, T2 -weighted and FLAIR images in human brain.

Dissolved oxygen has known paramagnetic effects in magnetic resonance imaging (MRI). The aim of this study was to compare the effects of normobaric oxygenation (NBO) and hyperbaric oxygenation (HBO) on human brain MRI signal intensities. Baseline brain MRI was performed in 17 healthy subjects (mean age 27.8 ± 3.2). MRI was repeated after exposure to the NBO and HBO at different time points (0 min, 25 min, 50 min). Signal intensities in T 1-weighted, T 2-weighted images and fluid attenuated inversion recovery (FLAIR) signal intensities of several intracranial structures were compared between NBO and HBO. Increased T 1-weighted signal intensities were observed in white and deep grey brain matter, cerebrospinal fluid (CSF), venous blood and vitreous body after exposure to NBO as well as to HBO compared to baseline (Dunnett's test, p < 0.05) without significant differences between both protocols. There was also no significant difference in T 2-weighted signal intensities between NBO and HBO. FLAIR signal intensities were increased only in the vitreous body after NBO and HBO and FLAIR signal of caudate nucleus was decreased after NBO (Dunnett's test, p < 0.05). The statistically significant differences in FLAIR signal intensities were found between NBO and HBO (paired t-test, p < 0.05) in most observed brain structures (paired t-test, p < 0.05). Our results show that NBO and HBO alters signal intensities T 1-weighted and FLAIR images of human brain. The differences between NBO and HBO are most pronounced in FLAIR imaging.

The diamagnetic component map from quantitative susceptibility mapping (QSM) source separation reveals pathological alteration in Alzheimer’s disease-driven neurodegeneration

A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.

Sjogren-Larsson syndrome brain volumetric reductions demonstrated with an automated software.

Sjogren-Larsson syndrome (SLS) is a neurocutaneous disease with an autosomal recessive inheritance, caused by mutations in the gene that encodes fatty aldehyde dehydrogenase (ALDH3A2), clinically characterized by ichthyosis, spastic diplegia, and cognitive impairment. Brain imaging plays an essential role in the diagnosis, demonstrating a nonspecific leukoencephalopathy. Data regarding brain atrophy and grey matter involvement is scarce and discordant. We performed a volumetric analysis of the brain of two siblings with SLS with the aim of detecting deep grey matter nuclei, cerebellar grey matter, and brainstem volume reduction in these patients. Volume data obtained from the brain magnetic resonance imaging (MRI) of the two patients using an automated segmentation software (Freesurfer) was compared with the volumes of a healthy control group. Statistically significant volume reduction was found in the cerebellum cortex, the brainstem, the thalamus, and the pallidum nuclei. Volume reduction in grey matter leads to the hypothesis that SLS is not a pure leukoencephalopathy. Grey matter structures affected in the present study suggest a dysfunction more prominent in the thalamic motor pathways.

Cerebellar deep brain stimulation for the treatment of movement disorders in cerebral palsy.

Cerebral palsy (CP) represents the most common childhood physical disability that encompasses disorders of movement and posture attributed to nonprogressive disturbances that occurred in the developmental fetal or infant brain. Dyskinetic CP (DCP), the second most common type of CP after spastic forms, refers to a subset of patients in whom dystonia and choreoathetosis are the predominant motor manifestations. Most children with CP have abnormal brain MRI studies indicative of cortical and deep gray matter damage consistent with hypoxic ischemic encephalopathy, which may preclude or suggest decreased efficacy of standard deep brain stimulation (DBS) targets. The cerebellum has been posited as an attractive target for treatment of DCP because it is frequently spared from hypoxic ischemic damage and has shown promise in alleviating patient symptoms both in early work in the 1970s and in more recent case series with DBS. The authors performed bilateral cerebellar DBS implantation, targeting the dentate nucleus (DN) and cerebellar outflow pathway, in 3 patients with DCP. Leads were connected to a pulse generator that senses local field potentials during chronic continuous DBS. The authors report their surgical methods, examples of chronic cerebellar local field potential recordings, and preliminary clinical outcomes. Motor outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale. Three patients 14-22 years old with DCP and MRI evidence of structural damage to the basal ganglia were offered cerebellar stimulation targeting the DN. All patients tolerated the procedure well and demonstrated improvement in subjective motor function as well as objective improvement in the Burke-Fahn-Marsden Dystonia Rating Scale movement subscale, although the range of responses was variable (19%-40%). Patients experienced subjective improvement in motor function including ease of hand movements and coordination, gait, head control, speech, decreased overflow, and diminished muscle tightness. DBS of the dentate nuclei in patients with DCP appears to be safe and shows preliminary evidence of clinical benefit. New chronic sensing technology may allow for determination of in vivo mechanisms of network disruption in DCP and allow for further understanding of the effects of neuromodulation on brain physiology. Larger studies with long-term follow up will be required to further elucidate the clinical benefits of this therapy. This report addresses a gap in the literature regarding the technical approach to image-based stereotactic targeting and chronic neural recording in the DN.

Evaluation of the correlation between thalamic area and cognitive functions in patients with early-stage relapsing-remitting multiple sclerosis

Background: The aim of this study is to investigate the presence of cognitive dysfunction and deep gray matter involvement in the early-stages of Relapsing-Remitting Multiple Sclerosis(RRMS) disease and examine the relationship between them.&#x0D; Materials and Methods: Thirty-four patients and 23 healthy individuals were included in the study. Patients diagnosed with RRMS according to the Revised 2010 and 2017 McDonald criteria, aged between 18-50, were enrolled in the study. The control group consisted of 23 healthy individuals with normal neurological examination, cranial magnetic resonance imaging(MRI), and cognitive functions. All participants underwent a neuropsychological test battery that covers memory, executive functions, language, and visuospatial domains, and the results of these tests were compared among the study groups. The data on MRI parameters, including the areas of the thalamus and corpus callosum as well as the width of the third ventricle, were compared among the study groups. Finally, the relationship between neuropsychological test results and MRI parameters was investigated in patients with early-stage RRMS.&#x0D; Results: The mean duration of the disease for MS patients was 3.53 years, and their median EDSS score was 2. It was observed that memory, executive functions, and fine motor skills were affected in early-stage RRMS patients. This impairment correlated with a decrease in the thalamus and corpus callosum areas and an increase in the third ventricle width.&#x0D; Conclusion: The MRI parameters defined as biomarkers for potential cognitive impairments in RRMS have critical importance in predicting the prognosis of the disease and taking early measures against future cognitive dysfunction.

Cortical thickness and cognition in older people with multiple sclerosis.

The structural changes associated with cognitive performance in older people with multiple sclerosis (PwMS; age ≥ 50years old) remain unknown. To determine the relationship between whole-brain (WBV), thalamus as the largest deep gray matter nuclei, and cortex-specific volume measurements with both cognitive impairment and numerical performance in older PwMS. The main hypothesis is that cognitive impairment (CI) in older PwMS is explained by cortical thinning in addition to global and thalamic neurodegenerative changes. A total of 101 older PwMS underwent cognitive and neuroimaging assessment. Cognitive assessment included tests established as sensitive in MS samples (Minimal Assessment of Cognitive Function in MS; MACFIMS), as well as those tests often utilized in Alzheimer's dementia studies (Wechsler's Memory Scale, Boston Naming Test, Visual Motor Integration and language). Cognitive impairment (CI) was based on -1.5 standard deviations in at least 2 cognitive domains (executive function, learning and memory, spatial processing, processing speed and working memory and language) when compared to healthy controls. WBV and thalamic volume were calculated using SIENAX/FIRST and cortical thickness using FreeSurfer. Differences in cortical thickness between CI and cognitively preserved (CP) were determined using age, sex, education, depression and WBV-adjusted analysis of covariance (ANCOVA). The relationship between domain-specific cognitive performance and cortical thickness was analyzed by linear regression models adjusted for age, sex, education, depression, WBV and thalamic volume. Benjamini-Hochberg-adjusted p-values lower than 0.05 were considered significant. The average age of the study population was 62.6 (5.9) years old. After adjustment, CI PwMS had significantly thinner left fusiform (p = 0.0003), left inferior (p = 0.0032), left transverse (p = 0.0013), and bilateral superior temporal gyri (p = 0.002 and p = 0.0011) when compared to CP PwMS. After adjusting for age, sex, education, depression WBV, and thalamic volume, CI status was additionally predicted by the thickness of the left fusiform (p = 0.001) and left cuneus gyri (p = 0.004). After the adjustment, SDMT scores were additionally associated with left fusiform gyrus (p < 0.001) whereas letter-based verbal fluency performance with left pars opercularis gyrus (p < 0.001). In addition to global and thalamic neurodegenerative changes, the presence of CI in older PwMS is additionally explained by the thickness of multiple cortical regions.