Measuring iron in the brain using quantitative susceptibility mapping and X-ray fluorescence imaging

Abstract

Measuring iron content in the brain has important implications for a number of neurodegenerative diseases. Quantitative susceptibility mapping (QSM), derived from magnetic resonance images, has been used to measure total iron content in vivo and in post mortem brain. In this paper, we show how magnetic susceptibility from QSM correlates with total iron content measured by X-ray fluorescence (XRF) imaging and by inductively coupled plasma mass spectrometry (ICPMS). The relationship between susceptibility and ferritin iron was estimated at 1.10±0.08 ppb susceptibility per μg iron/g wet tissue, similar to that of iron in fixed (frozen/thawed) cadaveric brain and previously published data from unfixed brains. We conclude that magnetic susceptibility can provide a direct and reliable quantitative measurement of iron content and that it can be used clinically at least in regions with high iron content.

Fig. 1

Photograph of the cadaveric brain sample in gelatin.

Fig. 2

Removing the background phase (TE = 21.73 ms). A) Geometry of the straws segmented from the spin echo images. B) Original phase. C) Background phase after extrapolation of magnetic fields into the straw regions. D) Subtraction of C from B to reveal pristine dipole effects due to the iron in the straws.

Fig. 3

Correlation between susceptibility measured by MRI and total iron measured by ICPMS and XRF for ferritin phantoms.

Fig. 4

Iron quantified from XRF Fe mapping (A, B) for left and right hemispheres; putative iron quantified as susceptibility (TE = 8.25 ms) (C, D). Images are co-registered and the ROIs used for a pixel by pixel correlation are outlined in both images. CN: caudate nucleus. PUT: putamen. GP: globus pallidus. ROIs were defined by excluding the edges in the map for each structure.

Fig. 5

Correlation between susceptibility and XRF iron measurements for all data points taken from each of the regions demarcated in Fig. 4. A: fitting for left hemisphere; B: fitting for right hemisphere.