Biophysical contrast sources for magnetic susceptibility and R2 mapping: A combined 7 Tesla, mass spectrometry and electron paramagnetic resonance study
•R2* and QSM show variable regional contrast patterns. With similar contrast in iron-rich structures.•Iron and its molecular form as ferritin were shown to be the main contributors for the overall R2* and QSM contrast.•Analysis individualized by ROI showed different contributions of iron and ferriti...
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| Published in | NeuroImage (Orlando, Fla.) Vol. 302; p. 120892 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Elsevier Inc
15.11.2024
Elsevier Limited Elsevier |
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| Abstract | •R2* and QSM show variable regional contrast patterns. With similar contrast in iron-rich structures.•Iron and its molecular form as ferritin were shown to be the main contributors for the overall R2* and QSM contrast.•Analysis individualized by ROI showed different contributions of iron and ferritin to R2* and QSM, resulting in three groups of structures according to the correlation of iron/ferritin to R2* and QSM.•Iron-rich structures displayed strong correlation to iron/ferritin, low-iron structures displayed no correlation to iron/ferritin, and the substantia nigra displayed partial correlation to iron and no correlation to ferritin.
Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R2* and QSM were calculated. We found that R2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R2*. This study demonstrated the quantitative correlations between R2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. |
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| AbstractList | Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R
* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26-91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R
* and QSM were calculated. We found that R
* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R
*. This study demonstrated the quantitative correlations between R
*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R₂* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R₂* and QSM were calculated. We found that R₂* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R₂*. This study demonstrated the quantitative correlations between R₂*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. •R2* and QSM show variable regional contrast patterns. With similar contrast in iron-rich structures.•Iron and its molecular form as ferritin were shown to be the main contributors for the overall R2* and QSM contrast.•Analysis individualized by ROI showed different contributions of iron and ferritin to R2* and QSM, resulting in three groups of structures according to the correlation of iron/ferritin to R2* and QSM.•Iron-rich structures displayed strong correlation to iron/ferritin, low-iron structures displayed no correlation to iron/ferritin, and the substantia nigra displayed partial correlation to iron and no correlation to ferritin. Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R2* and QSM were calculated. We found that R2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R2*. This study demonstrated the quantitative correlations between R2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R2* and QSM were calculated. We found that R2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R2*. This study demonstrated the quantitative correlations between R2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26-91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R2* and QSM were calculated. We found that R2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R2*. This study demonstrated the quantitative correlations between R2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation.Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26-91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R2* and QSM were calculated. We found that R2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R2*. This study demonstrated the quantitative correlations between R2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R 2 * mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R 2 * and QSM were calculated. We found that R 2 * and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R 2 > 0.7) and ferritin (R 2 > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R 2 > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R 2 * . This study demonstrated the quantitative correlations between R 2 * , QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R 2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R 2* and QSM were calculated. We found that R 2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R 2*. This study demonstrated the quantitative correlations between R 2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation. |
| ArticleNumber | 120892 |
| Author | Otsuka, Fábio Seiji Langkammer, Christian Rodriguez, Roberta Diehl Barbosa, Jeam Haroldo Oliveira Salmon, Carlos Ernesto Garrido Otaduy, Maria Concepción Garcia |
| AuthorAffiliation | d Setor de Radioterapia, Santa Casa de Misericórdia de Lavras, Minas Gerais, Brazil e Departamento de Imagens Médicas, Hematologia e Oncologia Clínica, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de Sãoo Paulo, Ribeirão Preto, Brazil c Department of Neurology, Medical University of Graz, Graz, Austria a InBrain, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo USP, Avenida Bandeirantes 3900, Vila Monte Alegre, Ribeirão Preto, São Paulo CEP 14040-901, Brazil b LIM44, Instituto de Radiologia (InRad), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, São Paulo, Brazil |
| AuthorAffiliation_xml | – name: b LIM44, Instituto de Radiologia (InRad), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, São Paulo, Brazil – name: a InBrain, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo USP, Avenida Bandeirantes 3900, Vila Monte Alegre, Ribeirão Preto, São Paulo CEP 14040-901, Brazil – name: e Departamento de Imagens Médicas, Hematologia e Oncologia Clínica, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de Sãoo Paulo, Ribeirão Preto, Brazil – name: c Department of Neurology, Medical University of Graz, Graz, Austria – name: d Setor de Radioterapia, Santa Casa de Misericórdia de Lavras, Minas Gerais, Brazil |
| Author_xml | – sequence: 1 givenname: Fábio Seiji orcidid: 0000-0001-6987-3270 surname: Otsuka fullname: Otsuka, Fábio Seiji email: fabio.otsuka@alumni.usp.br organization: InBrain, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo USP, Avenida Bandeirantes 3900, Vila Monte Alegre, Ribeirão Preto, São Paulo CEP 14040-901, Brazil – sequence: 2 givenname: Maria Concepción Garcia surname: Otaduy fullname: Otaduy, Maria Concepción Garcia organization: LIM44, Instituto de Radiologia (InRad), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, São Paulo, Brazil – sequence: 3 givenname: Roberta Diehl surname: Rodriguez fullname: Rodriguez, Roberta Diehl organization: LIM44, Instituto de Radiologia (InRad), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, São Paulo, Brazil – sequence: 4 givenname: Christian orcidid: 0000-0002-7097-9707 surname: Langkammer fullname: Langkammer, Christian organization: Department of Neurology, Medical University of Graz, Graz, Austria – sequence: 5 givenname: Jeam Haroldo Oliveira surname: Barbosa fullname: Barbosa, Jeam Haroldo Oliveira organization: InBrain, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo USP, Avenida Bandeirantes 3900, Vila Monte Alegre, Ribeirão Preto, São Paulo CEP 14040-901, Brazil – sequence: 6 givenname: Carlos Ernesto Garrido orcidid: 0000-0003-1441-1524 surname: Salmon fullname: Salmon, Carlos Ernesto Garrido email: garrido@ffclrp.usp.br organization: InBrain, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP), Universidade de São Paulo USP, Avenida Bandeirantes 3900, Vila Monte Alegre, Ribeirão Preto, São Paulo CEP 14040-901, Brazil |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39433113$$D View this record in MEDLINE/PubMed |
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| Keywords | R2 Quantitative susceptibility mapping Iron Ferritin Magnetic susceptibility R |
| Language | English |
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| Snippet | •R2* and QSM show variable regional contrast patterns. With similar contrast in iron-rich structures.•Iron and its molecular form as ferritin were shown to be... Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism,... |
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| SubjectTerms | Adult Aged Aged, 80 and over Algorithms atomic absorption spectrometry Basal ganglia Brain Brain - diagnostic imaging Brain - metabolism Brain mapping death electron paramagnetic resonance spectroscopy Electron spin resonance Electron Spin Resonance Spectroscopy - methods Female Ferritin Ferritins - analysis Ferritins - metabolism Gray Matter - diagnostic imaging Gray Matter - metabolism hippocampus Humans Iron Iron - analysis Iron - metabolism Magnetic resonance imaging Magnetic Resonance Imaging - methods Magnetic susceptibility Male Mass spectrometry Mass Spectrometry - methods Mass spectroscopy Middle Aged Neurological diseases paramagnetism postmortem changes Quantitative susceptibility mapping Red nucleus Scientific imaging Software Substantia grisea Substantia nigra |
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| Title | Biophysical contrast sources for magnetic susceptibility and R2 mapping: A combined 7 Tesla, mass spectrometry and electron paramagnetic resonance study |
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