MRI R2 and quantitative susceptibility mapping in brain tissue with extreme iron overload

Background R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear...

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Vydané v:	European radiology experimental Ročník 9; číslo 1; s. 80 - 13
Hlavní autori:	Birkl, Christoph, Panzer, Marlene, Kames, Christian, Birkl-Toeglhofer, Anna Maria, Rauscher, Alexander, Glodny, Bernhard, Gizewski, Elke R., Zoller, Heinz
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Vienna Springer Vienna 23.08.2025 Springer Nature B.V SpringerOpen
Predmet:	Adult Algorithms Alzheimer's disease Brain Brain - diagnostic imaging Brain - metabolism Ceruloplasmin Ceruloplasmin - deficiency Diagnostic Radiology Disease Female Humans Imaging Internal Medicine Interventional Radiology Iron Iron Metabolism Disorders - diagnostic imaging Iron overload Iron Overload - diagnostic imaging Magnetic fields Magnetic resonance imaging Magnetic Resonance Imaging - methods Male Medicine Medicine & Public Health Middle Aged Multiple sclerosis Neurodegenerative Diseases - diagnostic imaging Neuroradiology Original Original Article Patients Putamen Radiology Statistical analysis Tissues Ultrasound Ceruloplasmin Iron overload Brain Magnetic resonance imaging Putamen
ISSN:	2509-9280, 2509-9280
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Abstract	Background R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls. Materials and methods We acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus. Results R2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm). Conclusion Extreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload. Relevance statement As QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences. Key Points R2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail. Graphical Abstract
AbstractList	Abstract Background R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls. Materials and methods We acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus. Results R2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm). Conclusion Extreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload. Relevance statement As QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences. Key Points R2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail. Graphical Abstract Background R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls. Materials and methods We acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus. Results R2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm). Conclusion Extreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload. Relevance statement As QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences. Key Points R2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail. Graphical Abstract R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls. We acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus. R2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm). Extreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload. As QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences. R2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail. R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls.BACKGROUNDR2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls.We acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus.MATERIALS AND METHODSWe acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus.R2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm).RESULTSR2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm).Extreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload.CONCLUSIONExtreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload.As QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences.RELEVANCE STATEMENTAs QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences.R2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail.KEY POINTSR2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail. BackgroundR2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls.Materials and methodsWe acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus.ResultsR2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm).ConclusionExtreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload.Relevance statementAs QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences.Key PointsR2* and QSM vary across algorithms in brain tissue with iron overload.Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients.QSM, if properly processed, provides reliable maps in iron overload brain regions.In brain regions with extremely high iron content, R2* mapping might fail.
ArticleNumber	80
Author	Birkl-Toeglhofer, Anna Maria Glodny, Bernhard Gizewski, Elke R. Zoller, Heinz Panzer, Marlene Rauscher, Alexander Birkl, Christoph Kames, Christian
Author_xml	– sequence: 1 givenname: Christoph orcidid: 0000-0003-3101-4002 surname: Birkl fullname: Birkl, Christoph email: christoph.birkl@i-med.ac.at organization: Department of Radiology, Medical University of Innsbruck, Neuroimaging Research Core Facility, Medical University of Innsbruck – sequence: 2 givenname: Marlene surname: Panzer fullname: Panzer, Marlene organization: Department of Medicine I, Medical University of Innsbruck, Christian Doppler Laboratory for Iron and Phosphate Biology, Medical University of Innsbruck – sequence: 3 givenname: Christian surname: Kames fullname: Kames, Christian organization: Department of Physics and Astronomy, University of British Columbia – sequence: 4 givenname: Anna Maria surname: Birkl-Toeglhofer fullname: Birkl-Toeglhofer, Anna Maria organization: Institute of Neuropathology and Neuromolecular Pathology, Medical University of Innsbruck – sequence: 5 givenname: Alexander surname: Rauscher fullname: Rauscher, Alexander organization: Department of Physics and Astronomy, University of British Columbia, Department of Pediatrics, University of British Columbia – sequence: 6 givenname: Bernhard surname: Glodny fullname: Glodny, Bernhard organization: Department of Radiology, Medical University of Innsbruck – sequence: 7 givenname: Elke R. surname: Gizewski fullname: Gizewski, Elke R. organization: Department of Radiology, Medical University of Innsbruck, Neuroimaging Research Core Facility, Medical University of Innsbruck – sequence: 8 givenname: Heinz surname: Zoller fullname: Zoller, Heinz organization: Department of Medicine I, Medical University of Innsbruck, Christian Doppler Laboratory for Iron and Phosphate Biology, Medical University of Innsbruck
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Keywords	Ceruloplasmin Iron overload Brain Magnetic resonance imaging Putamen
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Snippet	Background R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques... R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are... BackgroundR2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques... Abstract Background R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these...
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SubjectTerms	Adult Algorithms Alzheimer's disease Brain Brain - diagnostic imaging Brain - metabolism Ceruloplasmin Ceruloplasmin - deficiency Diagnostic Radiology Disease Female Humans Imaging Internal Medicine Interventional Radiology Iron Iron Metabolism Disorders - diagnostic imaging Iron overload Iron Overload - diagnostic imaging Magnetic fields Magnetic resonance imaging Magnetic Resonance Imaging - methods Male Medicine Medicine & Public Health Middle Aged Multiple sclerosis Neurodegenerative Diseases - diagnostic imaging Neuroradiology Original Original Article Patients Putamen Radiology Statistical analysis Tissues Ultrasound
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Title	MRI R2 and quantitative susceptibility mapping in brain tissue with extreme iron overload
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