scholarly journals Analysis of deep grey nuclei susceptibility in early childhood: a quantitative susceptibility mapping and R2* study at 3 Tesla

2021 ◽  
Author(s):  
Peter Raab ◽  
Stefan Ropele ◽  
Eva Bültmann ◽  
Rolf Salcher ◽  
Heinrich Lanfermann ◽  
...  
Keyword(s):  
Early Childhood ◽  
Caudate Nucleus ◽  
Grey Matter ◽  
Brain Mri ◽  
Iron Accumulation ◽  
Iron Deposition ◽  
3 Tesla ◽  
Brain Maturation ◽  
Brain Iron ◽  
Deep Grey Matter

Abstract Purpose Aging is the most significant determinant for brain iron accumulation in the deep grey matter. Data on brain iron evolution during brain maturation in early childhood are limited. The purpose of this study was to investigate age-related iron deposition in the deep grey matter in children using quantitative susceptibility (QSM) and R2* mapping. Methods We evaluated brain MRI scans of 74 children (age 6–154 months, mean 40 months). A multi-echo gradient-echo sequence obtained at 3 Tesla was used for the QSM and R2* calculation. Susceptibility of the pallidum, head of caudate nucleus, and putamen was correlated with age and compared between sexes. Results Susceptibility changes in all three nuclei correlated with age (correlation coefficients for QSM/R2*: globus pallidus 0.955/0.882, caudate nucleus 0.76/0.65, and putamen 0.643/0.611). During the first 2 years, the R2* values increased more rapidly than the QSM values, indicating a combined effect of iron deposition and myelination, followed by a likely dominating effect of iron deposition. There was no significant gender difference. Conclusion QSM and R2* can monitor myelin maturation processes and iron accumulation in the deep grey nuclei of the brain in early life and may be a promising tool for the detection of deviations of this normal process. Susceptibility in the deep nuclei is almost similar early after birth and increases more quickly in the pallidum. The combined use of QSM and R2* analysis is beneficial.

Deep grey matter iron accumulation in alcohol use disorder

NeuroImage ◽  
2017 ◽  
Vol 148 ◽  
pp. 115-122 ◽  
Author(s):  
Michal Juhás ◽  
Hongfu Sun ◽  
Matthew R.G. Brown ◽  
Marnie B. MacKay ◽  
Karl F. Mann ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Grey Matter ◽  
Iron Accumulation ◽  
Deep Grey Matter

scholarly journals Brain MRI Pattern Recognition in Neurodegeneration With Brain Iron Accumulation

2020 ◽  
Vol 11 ◽  
Author(s):  
Jae-Hyeok Lee ◽  
Ji Young Yun ◽  
Allison Gregory ◽  
Penelope Hogarth ◽  
Susan J. Hayflick
Keyword(s):  
Pattern Recognition ◽  
Brain Mri ◽  
Iron Accumulation ◽  
Brain Iron

Deep grey matter `black T2` on 3 tesla magnetic resonance imaging correlates with disability in multiple sclerosis

2007 ◽  
Vol 13 (7) ◽  
pp. 880-883 ◽  
Author(s):  
Y. Zhang ◽  
RK Zabad ◽  
X. Wei ◽  
LM Metz ◽  
MD Hill ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Caudate Nucleus ◽  
Signal Intensity ◽  
Grey Matter ◽  
Expanded Disability Status Scale ◽  
Resonance Imaging ◽  
Disability Status ◽  
Deep Grey Matter

T2 hypointensity (black T2, BT2) in the deep grey matter of multiple sclerosis (MS) patients correlate weakly with disability at 1.5 T. BT2 is likely to be caused by abnormal iron deposition. We compared the correlation between disability and deep grey matter BT2 measured on 3 T MRI and on 1.5 T MRI in 17 MS patients. We observed a significant correlation between expanded disability status scale and signal intensity on 3 T MRI in the globus pallidus and the caudate nucleus ( r = —0.5, P < 0.05). BT2 at 3 T may be a useful MRI measure associated with disability in MS and warrants further study. Multiple Sclerosis 2007; 13: 880—883. http://msj.sagepub.com

Quantitative assessment of brain iron by R2* relaxometry in patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis

2009 ◽  
Vol 15 (9) ◽  
pp. 1048-1054 ◽  
Author(s):  
M Khalil ◽  
C Enzinger ◽  
C Langkammer ◽  
M Tscherner ◽  
M Wallner-Blazek ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Basal Ganglia ◽  
Quantitative Assessment ◽  
Disease Duration ◽  
Clinically Isolated Syndrome ◽  
Iron Accumulation ◽  
Iron Deposition ◽  
Relaxation Rates ◽  
Brain Iron ◽  
Relapsing Remitting

Background Increased iron deposition has been implicated in the pathophysiology of multiple sclerosis (MS), based on visual analysis of signal reduction on T2-weighted images. R2* relaxometry allows to assess brain iron accumulation quantitatively. Objective To investigate regional brain iron deposition in patients with a clinically isolated syndrome (CIS) or relapsing–remitting MS (RRMS) and its associations with demographical, clinical, and conventional magnetic resonance imaging (MRI) parameters. Methods We studied 69 patients (CIS, n = 32; RRMS, n = 37) with 3T MRI and analyzed regional R2* relaxation rates and their correlations with age, disease duration, disability, T2 lesion load, and normalized brain volumes. Results Basal ganglia R2* relaxation rates increased in parallel with age ( r = 0.3–0.6; P < 0.01) and were significantly higher in RRMS than in CIS ( P < 0.05). Using multivariate linear regression analysis, the rate of putaminal iron deposition was independently predicted by the patients’ age, disease duration, and gray matter atrophy. Conclusions Quantitative assessment by R2* relaxometry suggests increased iron deposition in the basal ganglia of MS patients, which is associated with disease duration and brain atrophy. This technique together with long-term follow-up thus appears suited to clarify whether regional iron accumulation contributes to MS morbidity or merely reflects an epiphenomenon.

Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in Clinically Isolated Syndrome

2012 ◽  
Vol 19 (7) ◽  
pp. 896-903 ◽  
Author(s):  
Ali M Al-Radaideh ◽  
Samuel J Wharton ◽  
Su-Yin Lim ◽  
Christopher R Tench ◽  
Paul S Morgan ◽  
...  
Keyword(s):  
Magnetic Susceptibility ◽  
Caudate Nucleus ◽  
Globus Pallidus ◽  
High Field ◽  
Grey Matter ◽  
Demyelinating Disease ◽  
Clinically Isolated Syndrome ◽  
Susceptibility Mapping ◽  
Ultra High Field ◽  
Deep Grey Matter

Objective:To determine, using ultra-high field magnetic resonance imaging (MRI), whether changes in iron content occur in the earliest phases of demyelinating disease, by quantifying the magnetic susceptibility of deep grey matter structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive of multiple sclerosis (MS), as compared with age-matched healthy subjects.Methods:We compared 19 CIS patients to 20 age-matched, healthy controls. Scanning of the study subjects was performed on a 7T Philips Achieva system, using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were first high-pass filtered, using a dipole fitting method, and then inverted to produce magnetic susceptibility maps. Region of interest (ROI) analysis was used to estimate magnetic susceptibility values for deep grey matter structures (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar).Results:Significantly increased relative susceptibilities were found in the CIS group, compared with controls, for the caudate nucleus ( p = < 0.01), putamen ( p < 0.01), globus pallidus ( p < 0.01) and pulvinar ( p < 0.05). We found no significant nor consistent trends in the relationship between susceptibility and age for either the study controls or CIS patients, in any ROI ( r2< 0.5; p > 0.05). In CIS patients, the time elapsed since the clinical event and the Expanded Disability Status Scale (EDSS) scores were not correlated with iron levels in any ROI ( r2< 0.5; p > 0.05); however, a moderate correlation ( r2= 0.3; p < 0.01) was found between the T1 lesion load and the mean susceptibility of the caudate nucleus.Conclusion:CIS patients showed an increased iron accumulation, as measured using susceptibility mapping of the deep grey matter, suggesting that iron changes did occur at the earlier stages of CIS disease.

scholarly journals Neurodegeneration with brain iron accumulation: A case report

2016 ◽  
Vol 10 (2) ◽  
pp. 160-164 ◽  
Author(s):  
Daniel Nassif ◽  
João Santos Pereira ◽  
Mariana Spitz ◽  
Cláudia Capitão ◽  
Alessandra Faria
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Autosomal Recessive ◽  
Psychiatric Symptoms ◽  
Brain Mri ◽  
Autosomal Recessive Disorder ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Diagnostic Importance ◽  
Abnormal Brain

ABSTRACT Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by mutation in the PANK2 gene. It is characterized by abnormal brain iron accumulation, mainly in the globus pallidus. PKAN is included in a group of disorders known as neurodegeneration with brain iron accumulation (NBIA). We report a case of atypical PKAN with its most characteristic presentation, exhibiting marked psychiatric symptoms, speech disorder and focal dystonia. Brain MRI has great diagnostic importance in this group of disorders and, in this case, disclosed the eye-of-the-tiger sign. Genetic testing confirmed the diagnosis.

scholarly journals Hemochromatosis mutations, dementia and brain iron deposition: a prospective cohort study

2020 ◽  
Author(s):  
David Melzer ◽  
Janice L Atkins ◽  
Luke C Pilling ◽  
Christine J Heales ◽  
Sharon Savage ◽  
...  
Keyword(s):  
Iron Overload ◽  
Gray Matter ◽  
Brain Mri ◽  
Iron Deposition ◽  
European Ancestry ◽  
Brain Iron ◽  
Incident Dementia ◽  
Gray Matter Volumes ◽  
Brain Iron Deposition

ABSTRACTImportanceBrain iron deposition is common in dementia, but its causal significance is uncertain. The HFE p.C282Y homozygous mutation in European ancestry populations can lead to iron overload and hemochromatosis, mainly in males. Data on brain outcomes in homozygotes are scarce.ObjectiveTo estimate HFE variant associations with MRI features plus incident dementia diagnoses during follow-up in a large community based cohort.DesignUK Biobank cohort with follow-up in routine hospitalization records (mean 8.8 years). MRI imaging available on a participant subset scanned 2014 to 2018.SettingCommunity cohort participants across England, Wales and Scotland.ParticipantsEuropean ancestry participants (n=451,186) aged 40 to 70 years at baseline, including 2,890 p.C282Y homozygotes (predominantly without baseline haemochromatosis diagnoses). MRI scanning on 9,464 males and 10,475 females, including 40 male and 75 female p.C282Y homozygotes.ExposureHFE C282Y and H63D genetic variantsMain outcome and measuresBrain MRI site specific T2* measures (lower values associated with iron deposition) and gray matter volumes. Incident dementia diagnoses during follow-up.ResultsMale p.C282Y homozygotes had lower T2* measures in several brain areas including the thalamus (beta = -1.04 standard deviations, 95% CI -1.33 to -0.76, multiple testing adjusted p-value=4.9*10-10), putamen and hippocampus, compared to those without HFE mutations. Male homozygotes also had smaller gray matter volumes in the putamen (beta -0.80 sd, 95%CI -1.12 to - 0.47, adjusted p=2.2*10-4) and ventral striatum.Diagnoses of incident dementia (Hazard Ratio HR=2.27; 95% CI 1.36 to 3.80, p=0.002) were more common in p.C282Y homozygous men, as were delirium diagnoses (HR=2.04, CI 1.09 to 3.82, p=0.03), but there was no association with Stroke.In p.C282Y homozygote females and p.C282Y/H63D heterozygotes, MRI associations were less marked.Conclusion and RelevanceIn a community sample, men with the HFE p.C282Y homozygote genotype had more brain iron deposition, smaller specific gray matter volumes, and increased incidence of dementia. As iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.Key PointsQuestionIs the hemochromatosis HFE p.C282Y homozygous variant in men associated with brain MRI features and incident dementia?FindingsOn MRI, p.C282Y homozygote males had evidence of more iron deposition in areas including the thalamus, putamen and hippocampus, plus smaller putamen gray matter volumes, compared to men without HFE mutations. In 451,186 UK Biobank participants during the mean 8.8 year follow-up, incident dementia diagnoses were more than twice as common in the 1,294 homozygous men.MeaningAs iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.

scholarly journals Diagnosing neurodegeneration with brain iron accumulation before iron starts to accumulate

2019 ◽  
pp. 17
Author(s):  
Ine Hoogwijs
Keyword(s):  
Genetic Testing ◽  
Brain Mri ◽  
Molecular Genetic ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Ataxic Gait ◽  
Myelinated Nerve ◽  
Axonal Spheroids ◽  
Elevated Liver Enzymes ◽  
Epilepsy Gene

Introduction Neurodegeneration with brain iron accumulation (NBIA) consists of a heterogeneous group of disorders with brain iron accumulation as common radiological endpoint. Mutations in multiple genes have been associated with NBIA. We present 2 cases with a different type of NBIA, in whom the diagnosis was confirmed before brain iron accumulation became evident on MRI.  Case description The first patient was referred because of frequent falls at the age of 4 years. She had an ataxic gait and weak Achilles tendon reflexes. Two years later, pyramidal and more prominent cerebellar signs became evident. A skin and muscle biopsy revealed intra-axonal spheroids in the peri-and endomysial myelinated nerve bundles as well as in the motor endplates, which led to the diagnosis of PLA2G6-associated neurodegeneration (PLAN). Brain iron accumulation occurred at follow-up MRI at 9 years of age. The second patient was referred because of developmental stagnation and detection of elevated liver enzymes at 3 months of age. Seizures started at 15 months of age, and were refractory to treatment with multiple anti-epileptic drugs. Molecular genetic testing using an epilepsy gene panel revealed a mutation in the WDR45 gene, a known cause of beta-propeller protein-associated neurodegeneration (BPAN). Brain MRI at 14 months of age showed diffuse hypomyelination in the absence of BIA.  Discussion This report highlights that NBIA can be suspected on a clinical basis and confirmed by genetic testing before iron accumulation becomes present on brain MRI. Early diagnosis will provide a longer timeframe for potential disease modulating treatments in the future.

scholarly journals Neurodegeneration with Brain Iron Accumulation Disorders: Valuable Models Aimed at Understanding the Pathogenesis of Iron Deposition

2019 ◽  
Vol 12 (1) ◽  
pp. 27 ◽  
Author(s):  
Sonia Levi ◽  
Valeria Tiranti
Keyword(s):  
Neurodegenerative Disorders ◽  
Clinical Symptoms ◽  
Experimental Models ◽  
Iron Accumulation ◽  
Iron Deposition ◽  
Brain Iron ◽  
Pathogenetic Mechanism ◽  
Human Phenotype ◽  
Iron Proteins ◽  
Brain Iron Deposition

Neurodegeneration with brain iron accumulation (NBIA) is a set of neurodegenerative disorders, which includes very rare monogenetic diseases. They are heterogeneous in regard to the onset and the clinical symptoms, while the have in common a specific brain iron deposition in the region of the basal ganglia that can be visualized by radiological and histopathological examinations. Nowadays, 15 genes have been identified as causative for NBIA, of which only two code for iron-proteins, while all the other causative genes codify for proteins not involved in iron management. Thus, how iron participates to the pathogenetic mechanism of most NBIA remains unclear, essentially for the lack of experimental models that fully recapitulate the human phenotype. In this review we reported the recent data on new models of these disorders aimed at highlight the still scarce knowledge of the pathogenesis of iron deposition.

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