Myelin and iron concentration in the human brain: a quantitative study of MRI contrast
Abstract
During the last five years ultra-high-field magnetic resonance imaging (MRI) has enabled an unprecedented view of living human brain. Brain tissue contrast in most MRI sequences is known to reflect mainly the spatial distributions of myelin and iron. These distributions have been shown to overlap significantly in many brain regions, especially in the cortex. It is of increasing interest to distinguish and identify cortical areas by their appearance in MRI, which has been shown to be feasible in vivo. Parcellation can benefit greatly from quantification of the independent contributions of iron and myelin to MRI contrast. Recent studies using susceptibility mapping claim to allow such a separation of the effects of myelin and iron in MRI. We show, using post-mortem human brain tissue, that this goal can be achieved. After MRI scanning of the block with appropriate T1 mapping and T2* weighted sequences, we section the block and apply a novel technique, proton induced X-ray emission (PIXE), to spatially map iron, phosphorus and sulfur elemental concentrations, simultaneously with 1μm spatial resolution. Because most brain phosphorus is located in myelin phospholipids, a calibration step utilizing element maps of sulfur enables semi-quantitative ex vivo mapping of myelin concentration. Combining results for iron and myelin concentration in a linear model, we have accurately modeled MRI tissue contrasts. Conversely, iron and myelin concentrations can now be estimated from appropriate MRI measurements in post-mortem brain samples.
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Methods developed for quantification, rather than visualisation, of molecules (PIXE and lipid mass spectrometry) could provide quantification of myelin for each imaging pixel, for example by estimating myelin concentration from sulfur and phosphorus.
“One solution to address the limitations of these commonly used metrics would be to employ methods developed for quantification, rather than visualisation, of molecules. These methods include proton induced X-ray emission (PIXE, Stüber et al. (2014)) and lipid mass spectrometry (González de San Román et al., 2018), which could provide quantification of myelin for each imaging pixel, for example by”
From Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology (2021) · cites this paper as Stüber et al. (2014)
With the exception of one study (Stüber et al., 2014), quantification methods such as PIXE and lipid mass spectrometry have not been used in the validation papers reviewed.
“With the exception of one study (Stüber et al., 2014), these methods have not been used in the validation papers we reviewed, but may be used in future studies to provide complementary information to traditional histological techniques.”
From Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology (2021) · cites this paper as Stüber et al., 2014
Postmortem factors such as the interval between death and fixation, and the known effects of the fixative on the tissue, can alter results.
“Postmortem factors, such as the interval between death and fixation, as well as the known effects of the fixative on the tissue can also alter results (18–21).”
From Superior Longitudinal Fasciculus: A Review of the Anatomical Descriptions With Functional Correlates (2022) · cites this paper as [20]
Many investigators regard R1 (1/T1) as the best MR measure of myelin content.
“many investigators consider R1 (1/T1) to be the best MR measure of myelin content (Stüber et al., 2014; Lutti et al., 2013).”
From Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise (2016) · cites this paper as Stüber et al., 2014
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De Guio, F., Reyes, S., Vignaud, A., Duering, M., Ropele, S., Duchesnay, E., Chabriat, H., & Jouvent, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106311 · Cited by 28 · see citing works
- Authors
- Stüber, C., Morawski, M., Schäfer, A., Labadie, C., Wähnert, M., Leuze, C., Streicher, M., Barapatre, N., Reimann, K., Geyer, S., Spemann, D., & Turner, R.
- Affiliations
- Max Planck Institute for Human Cognitive and Brain Sciences (DE)
- SUNY Upstate Medical University (US)
- Lyon 1 Université (FR)
- Leipzig University (DE)
- Corresponding author
- Stüber, Carsten
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 93
- Pages
- 95-106
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2071718644
- Cited by
- 635
- References
- 80
- Citations by year
- 2026: 55 · 2025: 44 · 2024: 48 · 2023: 58 · 2022: 72 · 2021: 76 · 2020: 53 · 2019: 47 · 2018: 56 · 2017: 48 · 2016: 44 · 2015: 27 · 2014: 6
- FWCI
- 32.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- European Commission
- Max-Planck-Institut für Kognitions- und Neurowissenschaften
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Physical Sciences › Physics and Astronomy › Nuclear and High Energy Physics › NMR spectroscopy and applications
- Keywords
- iron content, ultra-high field MRI, PIXE, elemental mapping, phosphorus, sulfur, cortical parcellation, susceptibility mapping, T1 mapping, T2-weighted imaging, postmortem brain
- MeSH terms
- Aged, Brain Chemistry, Female, Humans, Iron, Magnetic Resonance Imaging, Male, Middle Aged, Myelin Proteins
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