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Brain Iron Imaging Markers in the Presence of White Matter Hyperintensities

By Kyle D Murray, Md Nasir Uddin, Giovanni Schifitto, Jianhui Zhong

Posted 22 Mar 2021
bioRxiv DOI: 10.1101/2021.03.22.436449

Purpose: To investigate the relationship between pathological brain iron deposition and white matter hyperintensities (WMHs) in cerebral small vessel disease (CSVD), via Monte Carlo simulations of magnetic susceptibility imaging and a novel imaging marker called the Expected Iron Coefficient (EIC). Methods: A synthetic pathological model of a different number of impenetrable spheres at random locations was employed to represent pathological iron deposition. The diffusion process was simulated with a Monte Carlo method with adjustable parameters to manipulate sphere size, distribution, and extracellular properties. Quantitative susceptibility mapping (QSM) was performed in a clinical dataset to study CSVD to derive and evaluate QSM, R2*, the iron microenvironment coefficient (IMC), and EIC in the presence of WMHs. Results: The simulations show that QSM signals increase in the presence of increased tissue iron, confirming that the EIC increases with pathology. Clinical results demonstrate that while QSM, R2*, and the IMC do not show differences in brain iron, the EIC does in the context of CSVD. Conclusion: The EIC is more sensitive to subtle changes in brain iron deposition caused by pathology, even when QSM, R2*, and the IMC do not.

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