Iron Deposition Versus Demyelination: Chi-Separation Insights into Increased Magnetic Susceptibility in ALS Motor Cortex

Motivation: The role of iron deposition and demyelination in amyotrophic lateral sclerosis (ALS) remains poorly understood. Investigating these factors can provide crucial insights into disease mechanisms. Goal(s): To elucidate the contributions of iron deposition versus demyelination to increased magnetic susceptibility (χ) observed in the ALS motor cortex using Chi-separation. Approach: Applied Chi-separation to five patients, generating Chi-paramagnetic, Chi-diamagnetic, and Chi-total maps to differentiate the iron deposition from myelin content. Results: Chi-separation confirmed the elevated χ values on Chi-para while stable χ values on Chi-dia particularly in the precentral gyrus compared to the postcentral gyrus, indicating iron deposition and less myelin changes. Impact: This research clarifies the underlying mechanism driving changes in χ values in ALS using Chi-separation, emphasizing the predominant role of iron deposition over demyelination. Such insight highlights its potential for better understanding and potentially monitoring ALS progression.