Biophysical contrast sources for magnetic susceptibility and R2 mapping: A combined 7 Tesla, mass spectrometry and electron paramagnetic resonance study

• Published in: NeuroImage (Orlando, Fla.) Vol. 302; p. 120892
• Main Authors: Otsuka, Fábio Seiji, Otaduy, Maria Concepción Garcia, Rodriguez, Roberta Diehl, Langkammer, Christian, Barbosa, Jeam Haroldo Oliveira, Salmon, Carlos Ernesto Garrido
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2024; Elsevier Limited; Elsevier
• Subjects: 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; R2; Quantitative susceptibility mapping; Iron; Ferritin; Magnetic susceptibility; R
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2024.120892

•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.