Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging
Quantitative susceptibility mapping (QSM) is influenced by iron as well as myelin, which makes interpretation of pathologic changes challenging. Concurrent acquisition of MR sequences that are sensitive to axonal/myelin integrity, such as diffusion tensor imaging (DTI), may provide context for interpreting quantitative susceptibility (QS) signal. The purpose of our study was to investigate alterations in normal-appearing white matter (NAWM) in multiple sclerosis (MS) using QSM in conjunction with DTI.
Twenty relapsing–remitting MS patients and 20 age-matched healthy controls (HC) were recruited for this prospective study. QS, radial diffusivity (RD), fractional anisotropy (FA), and R2* maps within the whole brain as well as individual tracts were generated for comparison between NAWM and HC white matter (HCWM).
MS lesions demonstrated significant differences in QS, FA, RD, and R2* compared to HCWM (p < 0.03). These metrics did not show a significant difference between whole-brain NAWM and HCWM. Among NAWM tracts, the cingulate gyri demonstrated significantly decreased QS compared to HCWM (p = 0.004). The forceps major showed significant differences in FA and RD without corresponding changes in QS (p < 0.01).
We found discordant changes in QSM and DTI metrics within the cingulate gyri and forceps major. This may potentially reflect the influence of paramagnetic substrates such as iron, which could be decreased along these NAWM tracts. Our results point to the potential role of QSM as a unique biomarker, although additional validation studies are needed.
KeywordsQuantitative susceptibility mapping Multiple sclerosis Diffusion tensor imaging Normal-appearing white matter
The authors would like to acknowledge Dr. Wei Li for his invaluable help with the MRI protocol and data processing. The authors would also like to acknowledge Mr. Gilbert Gortez for his help with data collection.
Compliance with ethical standards
This work was funded, in part, by grants from the Conrad N. Hilton Foundation 17330 and the Radiological Society of North America Research Resident Grants RR1427 and RR1577.
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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