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. 2010 Feb 23;107(8):3834-9.
doi: 10.1073/pnas.0911177107. Epub 2010 Feb 3.

Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast

Affiliations

Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast

Masaki Fukunaga et al. Proc Natl Acad Sci U S A. .

Abstract

Recent advances in high-field MRI have dramatically improved the visualization of human brain anatomy in vivo. Most notably, in cortical gray matter, strong contrast variations have been observed that appear to reflect the local laminar architecture. This contrast has been attributed to subtle variations in the magnetic properties of brain tissue, possibly reflecting varying iron and myelin content. To establish the origin of this contrast, MRI data from postmortem brain samples were compared with electron microscopy and histological staining for iron and myelin. The results show that iron is distributed over laminae in a pattern that is suggestive of each region's myeloarchitecture and forms the dominant source of the observed MRI contrast.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Example of in vivo MRI contrast in the occipital lobe. (A) Localizer image shows region of interest for (B). (B) R2* weighted magnitude and frequency images. The frequency image reflecting resonance frequency shifts. Intracortical contrast is particularly strong in the frequency image, revealing the centrally located Line of Gennari (arrows).
Fig. 2.
Fig. 2.
Comparison of histochemical myelin and iron staining with MRI R2* data in the visual cortex. The myelin stain shows the characteristic density increase in the line of Gennari in the pericalcarine cortex (solid arrow). The V1/V2 boundaries are indicated by asterisks. A dashed line represents the calcarine fissure. The distribution of intracortical iron mimics that of myelin, with elevated iron in the line of Gennari. The MRI data show a striking similarity with the iron stain, with increased R2* in the line of Gennari (solid arrow), and in the deeper layers (open arrow), and subcortical white matter in area V2 (arrowhead).
Fig. 3.
Fig. 3.
Cellular colocalization of myelin and ferritin in the primary visual cortex. (A) Immunofluorescence costaining of MBP and ferritin protein shows strong colocalization in intracortical fibers on composite images (yellow in composite). The dashed lines represent gray/white matter boundaries. (Scale bar: 500 μm.) (B) Enlarged areas of superficial layers in the gray matter (sGM), the line of Gennari, deeper layers in the gray matter (dGM), and white matter (WM) all show widespread colocalization of MBP and ferritin. (Scale bar: 50 μm.) Image correlation between myelin and ferritin stains is indicated by r values.
Fig. 4.
Fig. 4.
Distribution of individual ferritin particles measured by EM. (A) Sample bright-field TEM image shows scattered foci of reduced signal intensity, presumably originating from ferritin particles (arrow). (B) EELS spectrum of a single particle confirms iron as source of TEM contrast. (C) STEM-EELS spectroscopic image (3.5 nm/pixel) of iron suggests particle sizes of 1 to 2 pixels, consistent with the range of 3 to 8 nm reported for the ferritin core size (13). (Scale bars: 100 nm in A, 50 nm in C.)
Fig. 5.
Fig. 5.
Effect of iron extraction on MRI contrast in postmortem brain tissue. Iron extraction strongly reduces intracortical magnetic susceptibility–based contrast as evidenced from R2*-weighted, R2*, and frequency shift images. The frequency images show subtle signs of contrast reversal with extraction, suggesting a small, opposing frequency shift caused by the remaining myelin. The circular area of susceptibility shift at right bottom of postextraction images is caused by an entrapped air bubble.

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