Quantitative susceptibility mapping as an early neuroimaging biomarker for amyotrophic lateral sclerosis: A review

Quantitative susceptibility mapping (QSM) is an advanced post-processing technique in magnetic resonance imaging that offers precise measurements of tissue magnetic susceptibility with impressive spatial resolution and sensitivity. This review examines the potential of QSM as a biomarker for early detection and monitoring of amyotrophic lateral sclerosis (ALS). Since 2015, studies have consistently reported increased QSM values in the motor regions of individuals with ALS, indicating significant iron deposition. Iron accumulation is associated with dysfunction of the upper motor neurons and faster disease progression. Notably, increased QSM values were also observed in the critical subcortical areas responsible for motor function and cognitive control. However, standardizing optimized protocols, including background field removal algorithms, phase unwrapping approaches, and methods for final susceptibility map reconstruction, has the potential to enhance the consistency and reliability of QSM as an ALS biomarker. Overall, the current body of evidence strongly supports QSM in detecting iron dysregulation associated with neurodegeneration in both motor and extra-motor regions in ALS. Furthermore, QSM's remarkable sensitivity to early pathological iron changes and its high specificity in distinguishing ALS positions make it a promising diagnostic and progression-tracking biomarker.