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|Title:||MAGNETIC RESONANCE IMAGING AND X-RAY FLUORESCENCE RAPID SCANNING: PROBES FOR NEURODEGENERATION|
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|Authors/Affiliations:||1 Richard McCrea*; 1 Helen Nichol; 1 Sheri Harder; |
1 University of Saskatchewan, Saskatoon, SK, Canada
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|Content:||Objectives: The unambiguous identification of neurodegenerative disorders prior to disease progression and post mortem pathological confirmation remains a goal for the medical imaging community. The development of noninvasive testing for these diseases is necessary for early identification, and treatment. Susceptibility weighted imaging (SWI) is a magnetic resonance (MR) protocol that utilizes phase in addition to magnitude information to identify areas of high magnetic susceptibility. These regions include tissue interfaces, and areas of high concentrations of paramagnetic metals, such as iron. Iron dysregulation has been shown to be involved in the disease process of several neurodegenerative disorders, such as Alzheimer and Parkinson disease but the sensitivity of MR for iron in these diseases is controversial. We address this using a new synchrotron technique, Rapid Scanning X-ray Fluorescence (RS-XRF) that quantitatively maps metals in whole brain slices. Our goal is to compare these iron maps to MRI to assess the sensitivity and resolution of new MR protocols like SWI to localize and quantify brain iron.|
Materials and Methods: Brains were selected post mortem based on physician diagnosis of Parkinson disease, and Progressive Supranuclear Palsy as a disease control. The brains were preserved in 10% formalin, and suspended in a 15% gelatin solution to reduce MR artifacts due to air bubbles. The gelatin blocks were scanned using a susceptibility weighted magnetic resonance imaging sequence with 0.5 cm slice across plane resolution. The scanned images were analyzed by a trained radiologist, and sections displaying non-standard pathology were selected for further study. Using the MR slice as a guide, the brains were cut and 2 mm thick slices prepared that best matched the MR image. RS-XRF was used to simultaneously map iron, zinc, copper, and manganese by measuring fluorescent photons within 200 eV of their K-alpha fluorescent peaks using a 11300 eV incident beam energy. Fluorescence counts were normalized to sample thickness and incident beam intensity using Matlab, and compared to several measured standards to provide a range of concentration.
Results: RS-XRF showed that the basal ganglia, putamen and caudate were rich in iron in both the PD and disease controls. MRI demonstrated a reduced intensity halo effect around the caudate, as well as several low signal areas throughout the basal ganglia, features which did not appear on the disease control. Several of these areas appeared to correlate to areas of excess iron by RS-XRF and so we explored if the chemical form of iron might be different. Several areas of high metal concentration were excised and scanned using microprobe and near edge spectra were obtained to determine the chemical form of the iron. We identified high levels of ferritin but other chemical forms of iron were present in low concentration.
Conclusion: We conclude that MRI can detect high levels of iron at low resolution. RS-XRF is a useful tool to evaluate the sensitivity of MR for brain iron.
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