Evidence map›Paper›PMID 34058334›Full record

ArticleNeuroImage2021

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.

Sara Lorio, Jan Sedlacik, Po-Wah So, Harold G Parkes, Roxana Gunny, Ulrike Löbel, Yao-Feng Li, Olumide Ogunbiyi, Talisa Mistry, Emma Dixon and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NeuroImage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Sara LorioDevelopmental Neurosciences, Great Ormond Street Institute of Child Health, University College London, London, UK; Wellcome EPSRC Centre for Medical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London SE1 7EH, UK.
Jan SedlacikBiomedical Engineering Department, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK; Center for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
Po-Wah SoDepartment of Neuroimaging, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
Harold G ParkesDepartment of Neuroimaging, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
Roxana GunnyDepartment of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Ulrike LöbelDepartment of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Yao-Feng LiDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London and Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; Pathology Department, Tri-Service General Hospital and National Defence Medical Centre, Taipei, Taiwan, ROC.
Olumide OgunbiyiDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London and Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Talisa MistryDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London and Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Emma DixonMRI Group, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
Sophie AdlerDevelopmental Neurosciences, Great Ormond Street Institute of Child Health, University College London, London, UK.
J Helen CrossDevelopmental Neurosciences, Great Ormond Street Institute of Child Health, University College London, London, UK.
Torsten BaldewegDevelopmental Neurosciences, Great Ormond Street Institute of Child Health, University College London, London, UK.
Thomas S JacquesDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London and Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Karin ShmueliMRI Group, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
David W CarmichaelDevelopmental Neurosciences, Great Ormond Street Institute of Child Health, University College London, London, UK; Wellcome EPSRC Centre for Medical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London SE1 7EH, UK. Electronic address: david.carmichael@kcl.ac.uk.

Funding

Wellcome TrustWellcome Trust 203148/Z/16/Z
6 · The paper itself

Abstract

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.

Indexed as

AdolescentBrain MappingCalciumCerebral CortexChildChild, PreschoolDrug Resistant EpilepsyFemaleGray MatterHumansImage Processing, Computer-AssistedIronMagnetic Resonance ImagingMaleMalformations of Cortical DevelopmentRetrospective StudiesCalciumIronZincBrain mineral contentDrug-resistant epilepsyFocal cortical dysplasiaMalformation of cortical developmentQuantitative magnetic susceptibility

Identifiers

PMID34058334
PMCPMC8350142

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.