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Synchrotron XRF imaging of Alzheimer’s disease basal ganglia reveals linear dependence of high-field magnetic resonance microscopy on tissue iron concentration

DOI: 10.1016/j.jneumeth.2019.03.002 DOI Help

Authors: Mary E. Finnegan (University of Warwick) , Naomi P. Visanji (Toronto Western Hospital) , Isolda Romero-canelon (University of Warwick) , Emily House (Lancaster University) , Surya Rajan (University of Warwick) , J. Frederick W. Mosselmans (Diamond Light Source) , Lili-naz Hazrati (The Hospital for Sick Children, Canada) , Jon Dobson (University of Florida) , Joanna F. Collingwood (Warwick University; University of Florida)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Neuroscience Methods

State: Published (Approved)
Published: March 2019
Diamond Proposal Number(s): 1125 , 7453

Open Access Open Access

Abstract: Background: Chemical imaging of the human brain has great potential for diagnostic and monitoring purposes. The heterogeneity of human brain iron distribution, and alterations to this distribution in Alzheimer’s disease, indicate iron as a potential endogenous marker. The influence of iron on certain magnetic resonance imaging (MRI) parameters increases with magnetic field, but is under-explored in human brain tissues above 7 T. New Method: Magnetic resonance microscopy at 9.4 T is used to calculate parametric images of chemically-unfixed post-mortem tissue from Alzheimer’s cases (n = 3) and healthy controls (n = 2). Iron-rich regions including caudate nucleus, putamen, globus pallidus and substantia nigra are analysed prior to imaging of total iron distribution with synchrotron X-ray fluorescence mapping. Iron fluorescence calibration is achieved with adjacent tissue blocks, analysed by inductively coupled plasma mass spectrometry or graphite furnace atomic absorption spectroscopy. Results: Correlated MR images and fluorescence maps indicate linear dependence of R2, R2* and R2’ on iron at 9.4 T, for both disease and control, as follows: [R2(s−1) = 0.072[Fe] + 20]; [R2*(s−1) = 0.34[Fe] + 37]; [R2’(s−1) = 0.26[Fe] + 16] for Fe in μg/g tissue (wet weight). Comparison with Existing Methods: This method permits simultaneous non-destructive imaging of most bioavailable elements. Iron is the focus of the present study as it offers strong scope for clinical evaluation; the approach may be used more widely to evaluate the impact of chemical elements on clinical imaging parameters. Conclusion: The results at 9.4 T are in excellent quantitative agreement with predictions from experiments performed at lower magnetic fields.

Journal Keywords: Alzheimer's; Imaging; Iron; MRI; Relaxometry; Synchrotron; X-ray fluorescence

Subject Areas: Biology and Bio-materials, Technique Development

Instruments: I18-Microfocus Spectroscopy