Quantifying iron content in magnetic resonance imaging

Ghassaban, Kiarash; Liu, Saifeng; Jiang, Caihong; Haacke, E. Mark

doi:10.1016/j.neuroimage.2018.04.047

Cited by 72 publications

(81 citation statements)

References 207 publications

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“…Our second hypothesis was that global changes in brain iron in the deep grey matter nuclei might be present in children with poorly controlled focal epilepsy compared to healthy control subjects. While we found a positive correlation between age and both χ and R2* values in deep brain nuclei, consistent with previous reports (HALLGREN and SOURANDER, 1958;Ordidge et al, 1994;Yao et al, 2009;Ashraf et al, 2018;Ghassaban et al, 2019), there was also a positive correlation with disease duration.…”

Section: Measurements Of Across Cortical Depth In Groups With Well-losupporting

confidence: 92%

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

Lorio

Sedlacik

et al. 2020

Preprint

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Objective Malformations 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 its 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. Methods QSM (χ) and R2* maps were calculated for 40 paediatric patients with suspected FCD (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* were performed within lesions, using a surface-based approach with comparison to homologous regions, and globally 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. Results Compared to fluid‐attenuated inversion recovery (FLAIR) or T1‐weighted imaging, QSM improved lesion conspicuity in 5% of patients. In patients with well-localised and confirmed FCDIIb 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 2-3mm 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, and decreased iron in the brain region exhibiting low χ and high R2*. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus, but these changes were not altered in epilepsy. Conclusion QSM 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. Theses findings suggests that the measurements of cortical χ measurements could be used to detect and delineate epilepsy lesions.

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Section: Measurements Of Across Cortical Depth In Groups With Well-losupporting

confidence: 92%

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

Lorio

Sedlacik

et al. 2020

Preprint

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“…Quantitative T2 mapping, for example, may not be adequately sensitive to detect changes driven by changes in NfL levels, explaining the lack of association. Alternative MRI techniques, such as multiparameter mapping 42 and quantitative susceptibility mapping, 43 may offer more sensitive and/or biologically specific approaches to further investigate the role of demyelination and iron toxicity in HD pathology.…”

Section: Discussionmentioning

confidence: 99%

Characterizing White Matter in Huntington's Disease

Gregory

Johnson

Byrne

et al. 2019

Movement Disord Clin Pract

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Background Background: Investigating early white matter (WM) change in Huntington's disease (HD) can improve our understanding of the way in which disease spreads from the striatum. Objectives Objectives: We provide a detailed characterization of pathology-related WM change in HD. We first examined WM microstructure using diffusion-weighted imaging and then investigated both underlying biological properties of WM and products of WM damage including iron, myelin plus neurofilament light, a biofluid marker of axonal degeneration-in parallel with the mutant huntingtin protein. MethodsMethods: We examined WM change in HD gene carriers from the HD-CSFcohort, baseline visit. We used standard-diffusion magnetic resonance imaging to measure metrics including fractional anisotropy, a marker of WM integrity, and diffusivity; a novel diffusion model (neurite orientation dispersion and density imaging) to measure axonal density and organization; T1-weighted and T2-weighted structural magnetic resonance imaging images to derive proxy iron content and myelin-contrast measures; and biofluid concentrations of neurofilament light (in cerebrospinal fluid (CSF) and plasma) and mutant huntingtin protein (in CSF). ResultsResults: HD gene carriers displayed reduced fractional anisotropy and increased diffusivity when compared with controls, both of which were also associated with disease progression, CSF, and mutant huntingtin protein levels. HD gene carriers also displayed proxy measures of reduced myelin contrast and iron in the striatum. Conclusion Conclusion: Collectively, these findings present a more complete characterization of HD-related microstructural brain changes. The correlation between reduced fractional anisotropy, increased axonal orientation, and biofluid markers suggest that axonal breakdown is associated with increased WM degeneration, whereas higher quantitative T2 signal and lower myelin-contrast may indicate a process of demyelination limited to the striatum.The ongoing development of novel therapeutics to treat Huntington's disease (HD) necessitates improved characterization of HD-related brain changes. HD is a progressive neurodegenerative disorder characterized by a motor, cognitive, and neuropsychiatric phenotype and caused by CAG expansions in the huntingtin gene (HTT). Given the certainty of onset in those that inherit the gene combined with genetic testing, we can examine brain changes from the earliest, presymptomatic disease stages.Magnetic resonance imaging (MRI) measures of neuronal atrophy have characterized macrostructural brain changes associated with HD progression. 1,2 Neurodegeneration primarily originates in the striatum, extending to white matter (WM) and finally the cortex. 1,3 However, although a robust marker of disease progression, macrostructural changes provide limited descriptions of pathological mechanisms underlying HD. Investigating early WM microstructural changes in HD can improve our understanding of WM organization

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“…For instance, vessel wall characterization is important to atherosclerosis (Coolen et al, 2017). The quantification of iron content in the human brain is important to the understanding of diseases like Parkinson and multiple sclerosis (Ghassaban, Liu, Jiang, & Haacke, 2018). Ultrahigh-field (UHF) MRI at 7 T nowadays impacts functional MRI, which benefits of increased resolution and also opens the door to the investigation of brain functions at a submillimeter scale (De Martino et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Intensity‐curvature functional‐based filtering in image space and k‐space: Applications in magnetic resonance imaging of the human brain

Ciulla

2019

High Frequency

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This research examines the use of the intensity‐curvature functional (ICF) as filter in image space and in k‐space. The novelty of this study is three‐folded: (a) The evidence that the ICF calculated from three additional (International Journal of Imaging Systems and Technology, 28, 2018, 54) two‐dimensional model polynomial functions is an image space filter; (b) An additional (The use of the intensity‐curvature functional as k‐space filter: Applications in magnetic resonance imaging of the human brain, 2018) ICF‐based k‐space filtering technique applicable to two‐dimensional magnetic resonance images; (c) Results obtained through the calculation of the ICF of the trivariate cubic Lagrange model polynomial function (LGR3D). Although ICF‐based k‐space filtering delivers clear and well‐defined images, ICF‐based image space filtering remains superior when reconstructing vessel images in T2 MRI. The ICF of the LGR3D function provides sharp images too.

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Quantifying iron content in magnetic resonance imaging

Cited by 72 publications

References 207 publications

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

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

Characterizing White Matter in Huntington's Disease

Intensity‐curvature functional‐based filtering in image space and k‐space: Applications in magnetic resonance imaging of the human brain

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