• Gut-muscle-brain axis
• Mechanisms
• Parkinson's disease
• Sarcopenia
• Therapy

• anaesthesia
• basal nucleus of Meynert
• cholinergic system
• delirium
• magnetic resonance imaging
• postoperative cognitive dysfunction
• surgery
• susceptibility weighted imaging

• Humans
• Female
• Male
• Aged
• Cognitive Dysfunction/etiology
• Cognitive Dysfunction/physiopathology
• Postoperative Complications
• Magnetic Resonance Imaging
• Delirium/etiology
• Brain/diagnostic imaging
• Brain/metabolism
• Aged, 80 and over
• Postoperative Cognitive Complications

• RF1 NS023945 NINDS NIH HHS
• R01 NS023945 NINDS NIH HHS
• Clinician Scientist Program Berlin Institute of Health
• 602461 European Commission
• European Union Seventh Framework Program
• Charité-Universitätsmedizin Berlin and the BIH at Charité

• Humans
• Down Syndrome/therapy
• Retrospective Studies
• Case-Control Studies
• Neuroimaging/methods
• Immunotherapy

• P30 DK048520 NIDDK NIH HHS

• Humans
• Child, Preschool
• Magnetic Resonance Imaging/methods
• Brain/diagnostic imaging
• Brain Mapping/methods
• Aging
• Iron

• Mean susceptibility value (MSV)
• Mineralization
• PSP rating scale (PSPRS)
• Progressive supranuclear palsy (PSP)
• Quantitative susceptibility mapping (QSM)

• Humans
• Supranuclear Palsy, Progressive/diagnostic imaging
• Parkinson Disease
• Substantia Nigra/diagnostic imaging
• Caudate Nucleus
• Patient Acuity
• Magnetic Resonance Imaging

• BT/PR19115/MED/122/11/2016 Department of Biotechnology, Ministry of Science and Technology, India

The present paper investigated the association of Parkinson’s disease etiology with phosphate toxicity, a pathophysiological condition in which dysregulated phosphate metabolism causes excessive inorganic phosphate sequestration in body tissue that damages organ systems. Excessive phosphate is proposed to reduce Complex I function of the mitochondrial electron transport chain in Parkinson’s disease and is linked to opening of the mitochondrial permeability transition pore, resulting in increased reactive oxygen species, inflammation, DNA damage, mitochondrial membrane depolarization, and ATP depletion causing cell death. Parkinson’s disease is associated with α-synuclein and Lewy body dementia, a secondary tauopathy related to hyperphosphorylation of tau protein, and tauopathy is among several pathophysiological pathways shared between Parkinson’s disease and diabetes. Excessive phosphate is also associated with ectopic calcification, bone mineral disorders, and low levels of serum vitamin D in patients with Parkinson’s disease. Sarcopenia and cancer in Parkinson’s disease patients are also associated with phosphate toxicity. Additionally, Parkinson’s disease benefits are related to low dietary phosphate intake. More studies are needed to investigate the potential mediating role of phosphate toxicity in the etiology of Parkinson’s disease.

• Calcium
• Computed tomography
• Globus pallidus
• Iron
• Quantitative susceptibility mapping

• iron
• magnetic resonance imaging
• aging
• alzheimer disease
• vascular dementia

• National Research Foundation of Korea
• Hankuk University of Foreign Studies

In recent studies, iron overload has been reported in atypical parkinsonian syndromes. The topographic patterns of iron distribution in deep brain nuclei vary by each subtype of parkinsonian syndrome, which is affected by underlying disease pathologies. In this study, we developed a novel framework that automatically analyzes the disease-specific patterns of iron accumulation using susceptibility weighted imaging (SWI). We constructed various machine learning models that can classify diseases using radiomic features extracted from SWI, representing distinctive iron distribution patterns for each disorder. Since radiomic features are sensitive to the region of interest, we used a combination of T1-weighted MRI and SWI to improve the segmentation of deep brain nuclei. Radiomics was applied to SWI from 34 patients with a parkinsonian variant of multiple system atrophy, 21 patients with cerebellar variant multiple system atrophy, 17 patients with progressive supranuclear palsy, and 56 patients with Parkinson’s disease. The machine learning classifiers that learn the radiomic features extracted from iron-reflected segmentation results produced an average area under receiver operating characteristic curve (AUC) of 0.8607 on the training data and 0.8489 on the testing data, which is superior to the conventional classifier with segmentation using only T1-weighted images. Our radiomic model based on the hybrid images is a promising tool for automatically differentiating atypical parkinsonian syndromes.

Brain iron load is one of the most important neuropathological hallmarks in movement disorders. Specifically, the iron provides most of the paramagnetic metal signals in the brain and its accumulation seems to play a key role, although not completely explained, in the degeneration of the basal ganglia, as well as other brain structures. Moreover, iron distribution patterns have been implicated in depicting different movement disorders. This work reviewed current literature on Magnetic Resonance Imaging for Brain Iron Detection and Quantification (MRI-BIDQ) in neurodegenerative processes underlying movement disorders.

The aim of the study was to investigate the possible influence of changes in the brain caused by age on relaxometric and relaxation time–weighted magnetic resonance imaging (MRI) parameters in the deep cerebellar nuclei (DCN) and the globus pallidus (GP) of Gd-exposed and control rats over the course of 1 year.

• COVID-19
• SARS-CoV-2
• UK Biobank (UKB)
• brain magnetic resonance imaging (MRI)
• multi-organ MRI

• MC_PC_17228 Medical Research Council
• MR/V027859/1 Medical Research Council
• MR/T033371/1 Medical Research Council
• 202788/Z/16/Z Wellcome Trust
• MR/M024962/1 Medical Research Council
• RE/18/3/34214 British Heart Foundation
• Wellcome Trust
• MC_EX_MR/N50192X/1 Medical Research Council
• MC_QA137853 Medical Research Council
• Engineering and Physical Sciences Research Council
• NIHR Oxford Biomedical Research Centre

• calcium, ex vivo, histology, iron, quantitative susceptibility mapping

• Aged
• Basal Ganglia/diagnostic imaging
• Basal Ganglia/pathology
• Calcinosis/diagnostic imaging
• Female
• Globus Pallidus/diagnostic imaging
• Globus Pallidus/pathology
• Humans
• Magnetic Resonance Imaging
• Male
• Tomography, X-Ray Computed

• AV-1451
• Flortaucipir
• Longitudinal tau pet
• Reference region
• Tau pet

Myelin loss and iron accumulation are cardinal features of aging and various neurodegenerative diseases. Oligodendrocytes incorporate iron as a metabolic substrate for myelin synthesis and maintenance. An emerging hypothesis in Alzheimer’s disease research suggests that myelin breakdown releases substantial stores of iron that may accumulate, leading to further myelin breakdown and neurodegeneration. We assessed associations between iron content and myelin content in critical brain regions using quantitative magnetic resonance imaging (MRI) on a cohort of cognitively unimpaired adults ranging in age from 21 to 94 years. We measured whole-brain myelin water fraction (MWF), a surrogate of myelin content, using multicomponent relaxometry, and whole-brain iron content using susceptibility weighted imaging in all individuals. MWF was negatively associated with iron content in most brain regions evaluated indicating that lower myelin content corresponds to higher iron content. Moreover, iron content was significantly higher with advanced age in most structures, with men exhibiting a trend towards higher iron content as compared to women. Finally, relationship between MWF and age, in all brain regions investigated, suggests that brain myelination continues until middle age, followed by degeneration at older ages. This work establishes a foundation for further investigations of the etiology and sequelae of myelin breakdown and iron accumulation in neurodegeneration and may lead to new imaging markers for disease progression and treatment.

• Aging
• Iron
• Myelin
• Quantitative MRI

• Iron
• MRI
• QSM
• concussion
• quantitative susceptibility mapping
• traumatic brain injury

• Aging
• Deep grey nuclei
• Healthy subjects
• MR imaging
• T2 gradient-echo hypointensity

• Magnetic resonance imaging
• Parkinson disease
• cerebral amyloid angiopathy
• dementia

• Age prediction
• Brain aging
• Canonical correlation analysis
• Machine learning
• Magnetic resonance imaging
• Magnetoencephalography

Pathological mineralization has been reported countless times in the literature and is a well-known phenomenon in the medical field for its connections to a wide range of diseases, including cancer, cardiovascular, and neurodegenerative diseases. The minerals involved in calcification, however, have not been directly studied as extensively as the organic components of each of the pathologies. These have been studied in isolation and, for most of them, physicochemical properties are hitherto not fully known. In a parallel development, materials science methods such as electron microscopy, spectroscopy, thermal analysis, and others have been used in biology mainly for the study of hard tissues and biomaterials and have only recently been incorporated in the study of other biological systems. This review connects a range of soft tissue diseases, including breast cancer, age-related macular degeneration, aortic valve stenosis, kidney stone diseases, and Fahr’s syndrome, all of which have been associated with mineralization processes. Furthermore, it describes how physicochemical material characterization methods have been used to provide new information on such pathologies. Here, we focus on diseases that are associated with calcium-composed minerals to discuss how understanding the properties of these minerals can provide new insights on their origins, considering that different conditions and biological features are required for each type of mineral to be formed. We show that mineralomics, or the study of the properties and roles of minerals, can provide information which will help to improve prevention methods against pathological mineral build-up, which in the cases of most of the diseases mentioned in this review, will ultimately lead to new prevention or treatment methods for the diseases. Importantly, this review aims to highlight that chemical composition alone cannot fully support conclusions drawn on the nature of these minerals.

• calcification
• ectopic calcification
• mineralomics
• minerals
• pathological mineralization

Objectives: To validate a visual rating scale reflecting sub-regional patterns of putaminal hypointensity in susceptibility-weighted imaging of patients with multiple system atrophy (MSA).

Methods: Using a visual rating scale (from G0 to G3), 2 examiners independently rated putaminal hypointensities of 37 MSA patients and 21 control subjects. To investigate the correlation with the scales, R2^* values and the volume of the entire putamen were measured.

Results: MSA patients with parkinsonian variant had significantly higher scores than those with cerebellar variant. Visual rating scores in MSA were correlated with R2^* values [General estimating equation (GEE), Wald chi-square = 25.89, corrected p < 0.001] and volume (Wald chi-square = 75.44, corrected p < 0.001). They correlated with UPDRS motor scores. Binary logistic regression analyses revealed that the visual rating scale was a significant predictor for discriminating MSA patients from controls [multivariate model adjusted for age and sex, odds ratio 52.722 (corrected p = 0.009)]. Pairwise comparison between areas under the curve (AUCs) revealed that the visual rating scale demonstrated higher accuracy than R2^* values [difference between AUCs; univariate model = 0.247 (corrected p < 0.001); multivariate model = 0.186 (corrected p = 0.003)]. There were no significant differences in clinical characteristics between the high-iron group, defined as putamen with visual rating scale ≥ G2 and R2^* values ≥ third quartile, and the remaining patients.

Conclusion: The visual rating scale, which reflects quantitative iron content and atrophy of the putamen as well as motor severities, could be useful for the discrimination and evaluation of patients with MSA.

• brain MR image
• multiple system atrophy
• putaminal hypointensity
• susceptibility weight imaging
• visual rating scale

Patients with Parkinson’s disease (PD) have elevated levels of brain iron, especially in the nigrostriatal dopaminergic system. The purpose of this study was to evaluate the iron deposition in the substantia nigra (SN) and other deep gray matter nuclei of PD patients using quantitative susceptibility mapping (QSM) and its clinical relationship, and to explore whether there is a gradient of iron deposition pattern in globus pallidus (GP)–fascicula nigrale (FN)–SN pathway.

Thirty-three PD patients and 26 age- and sex-matched healthy volunteers (HVs) were included in this study. Subjects underwent brain MRI and constructed QSM data. The differences in iron accumulation in the deep gray matter nuclei of the subjects were compared, including the PD group and the control group, the early-stage PD (EPD) group and the late-stage PD (LPD) group. The iron deposition pattern of the GP–FN–SN pathway was analyzed.

The PD group showed increased susceptibility values in the FN, substantia nigra pars compacta (SNc), internal globus pallidus (GPi), red nucleus (RN), putamen and caudate nucleus compared with the HV group (P < 0.05). In both PD and HV group, iron deposition along the GP–FN–SN pathway did not show an increasing gradient pattern. The SNc, substantia nigra pars reticulata (SNr) and RN showed significantly increased susceptibility values in the LPD patients compared with the EPD patients.

PD is closely related to iron deposition in the SNc. The condition of PD patients is related to the SNc and the SNr. There is not an increasing iron deposition gradient along the GP–FN–SN pathway. The source and mechanism of iron deposition in the SN need to be further explored, as does the relationship between the iron deposition in the RN and PD.

• Iron deposition
• Parkinson’s disease
• Quantitative susceptibility mapping

Recent data suggest mechanistic links among perturbed iron homeostasis, oxidative stress, and misfolded protein aggregation in neurodegenerative diseases. Iron overload and toxicity toward dopaminergic neurons have been established as playing a role in the pathogenesis of Parkinson's disease (PD). Brain iron accumulation has also been documented in atypical parkinsonian syndromes (APS), mainly comprising multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Iron-sensitive magnetic resonance imaging (MRI) has been applied to identify iron-related signal changes for the diagnosis and differentiation of these disorders. Topographic patterns of widespread iron deposition in deep brain nuclei have been described as differing between patients with MSA and PSP and those with PD. A disease-specific increase of iron occurs in the brain regions mainly affected by underlying disease pathologies. However, whether iron changes are a primary pathogenic factor or an epiphenomenon of neuronal degeneration has not been fully elucidated. Moreover, the clinical implications of iron-related pathology in APS remain unclear. In this review study, we collected data from qualitative and quantitative MRI studies on brain iron accumulation in APS to identify disease-related patterns and the potential role of iron-sensitive MRI.

• atypical parkinsonian syndromes
• iron
• magnetic resonance imaging
• multiple system atrophy
• neurodegeneration
• progressive supranuclear palsy

During the past several decades there has been much interest in the existence of magnetite particles in the human brain and their accumulation with age. These particles also appear to play an important role in neurodegenerative diseases of the brain. However, up to now the amount and distribution of these particles has been measured only in post‐mortem brain tissue. Although in‐vivo MRI measurements do show iron compounds generally, MRI cannot separate them according to their magnetic phases, which are associated with their chemical interactions. In contrast, we here offer a new noninvasive, in‐vivo method which is selectively sensitive only to particles which can be strongly magnetized. We magnetize these particles with a strong magnetic field through the head, and then measure the resulting magnetic fields, using the dcMagnetoencephalogram (dcMEG). From these data, the mass and locations of the particles can be estimated, using a distributed inverse solution. To test the method, we measured 11 healthy male subjects (ages 19–89 year). Accumulation of magnetite, in the hippocampal formation or nearby structures, was observed in the older men. These in‐vivo findings agree with reports of post‐mortem measurements of their locations, and of their accumulation with age. Thus, our findings allow in‐vivo measurement of magnetite in the human brain, and possibly open the door for new studies of neurodegenerative diseases of the brain.

• MEG
• MEG methods development
• brain aging

• Brain
• Ischemia
• Magnetic resonance imaging
• Quantitative susceptibility mapping
• Susceptibility weighted imaging

• R2*
• brain
• calcification
• epilepsy
• iron
• lesions
• quantitative susceptibility mapping

• Animals
• Calcium/metabolism
• Disease Models, Animal
• Iron/metabolism
• Magnetic Resonance Imaging/methods
• Male
• Rats
• Rats, Wistar
• Sensitivity and Specificity
• Status Epilepticus/metabolism
• Status Epilepticus/pathology
• Thalamus/diagnostic imaging
• Thalamus/metabolism
• Thalamus/pathology

• U54 HD079123 NICHD NIH HHS
• R03 EB017806 NIBIB NIH HHS
• K08 NS063956 NINDS NIH HHS
• R21 NS096249 NINDS NIH HHS
• P41 EB015909 NIBIB NIH HHS

• Perl's stain
• basal ganglia
• brain
• perivascular

Calcification has been well reported in basal ganglia and it grows rapidly in globus pallidus (GP) followed by putamen (PUT) and caudate nucleus because of their high metabolic rate and displays high susceptibility effects. Therefore, the current study focused on magnetic susceptibility effect of calcium content in normal and diseased tissue due to metabolic changes.

To evaluate calcium content in GP and PUT structures of multiple sclerosis (MS) patients versus healthy subjects using quantitative susceptibility mapping.

We compared 10 MS patients with mean age of 48.3 years (standard deviation [SD]=11.89) with 10 healthy subjects with mean age of 39.6 years (SD=11.52). Scanning of subjects was performed with high resolution (0.5×0.5×2 mm³) using susceptibility weighted imaging sequence on 3 Tesla (Trio-Siemens, Erlangen, Germany). Data was processed in homemade SPIN software to produce susceptibility mapping. Threshold was set in healthy subjects to detect calcium content in PUT and GP structures.

Magnetic susceptibility(x) of calcium content was assessed by number of pixels induced by GP and PUT in MS patients as well as healthy subjects. Two sample t-test was used to assess the difference between susceptibilities of GP and PUT of MS patients (P = 0.06, P > 0.05). Susceptibilities of GP and PUT also showed P = 0.3 in healthy subjects. One way analysis of variance was used to assess the difference of susceptibilities in four variables of both populations. Insignificant results (P = 0.7, P > 0.05) were found among four variables. There was no statistically significant difference between magnetic susceptibilities of both populations.

Statistical analysis of susceptibilities of MS patients versus healthy subjects found no excess deposition of calcium content in deep gray matter of MS patients. Calcification may not be considered as a biomarker of prognosis in MS.

• Basal Ganglia Calcification
• Brain Diseases
• Multiple Sclerosis

• imaging
• parkinsonian disorders
• susceptibility-weighted mri

• Aged
• Brain/diagnostic imaging
• Female
• Humans
• Imaging, Three-Dimensional
• Magnetic Resonance Imaging/methods
• Male
• Parkinsonian Disorders/diagnostic imaging

• Adult
• Aged
• Basal Ganglia/pathology
• Basal Ganglia/physiopathology
• Brain Mapping/methods
• Disease Progression
• Female
• Humans
• Iron/analysis
• Magnetic Resonance Imaging/methods
• Male
• Middle Aged
• Multiple Sclerosis/pathology
• Multiple Sclerosis/physiopathology

• Acute hepatic encephalopathy
• Microhemorrhage
• Susceptibility weighted imaging

Multifocal basal ganglia T2*-weighted (T2*w) hypointensities, which are believed to arise mainly from vascular mineralization, were recently proposed as a novel MRI biomarker for small vessel disease and ageing. These T2*w hypointensities are typically segmented semi-automatically, which is time consuming, associated with a high intra-rater variability and low inter-rater agreement. To address these limitations, we developed a fully automated, unsupervised segmentation method for basal ganglia T2*w hypointensities. This method requires conventional, co-registered T2*w and T1-weighted (T1w) volumes, as well as region-of-interest (ROI) masks for the basal ganglia and adjacent internal capsule generated automatically from T1w MRI. The basal ganglia T2*w hypointensities were then segmented with thresholds derived with an adaptive outlier detection method from respective bivariate T2*w/T1w intensity distributions in each ROI. Artefacts were reduced by filtering connected components in the initial masks based on their standardised T2*w intensity variance. The segmentation method was validated using a custom-built phantom containing mineral deposit models, i.e. gel beads doped with 3 different contrast agents in 7 different concentrations, as well as with MRI data from 98 community-dwelling older subjects in their seventies with a wide range of basal ganglia T2*w hypointensities. The method produced basal ganglia T2*w hypointensity masks that were in substantial volumetric and spatial agreement with those generated by an experienced rater (Jaccard index = 0.62 ± 0.40). These promising results suggest that this method may have use in automatic segmentation of basal ganglia T2*w hypointensities in studies of small vessel disease and ageing.

•

A novel method segmented focal T2*-weighted MRI hypointensities automatically.

• Ageing
• Automated segmentation
• Basal ganglia
• Focal T2*-weighted MRI hypointensities
• Magnetic resonance imaging (MRI)
• Mineralization
• Outlier detection

• alprostadil
• erectile dysfunction
• prostate cancer
• validation