A specific biomarker for amyotrophic lateral sclerosis: Quantitative susceptibility mapping


      • Motor cortex quantitative susceptibility values were significantly higher in ALS patients compared to patients without motor neuron symptoms.
      • Significantly higher motor cortex quantitative susceptibility values were found in ALS patients compared to patients with diseases mimicking ALS.
      • Measurements along the hand homunculus showed 100% specificity in differentiating ALS from mimics.
      • Quantitative susceptibility mapping has a diagnostic role in differentiating ALS from disease mimics.



      Accurate and timely diagnosis of amyotrophic lateral sclerosis (ALS) is a diagnostic challenge given the lack of specific diagnostic and imaging biomarkers as well as the significant clinic overlap with mimic syndromes. We hypothesize that MR quantitative susceptibility mapping (QSM) can help differentiate ALS from mimic diagnoses.


      In a blinded retrospective study of MRIs with QSM from 2015 to 2018, we compared motor cortex susceptibility along the hand and face homunculi in ALS patients and patients with similar clinical presentations. Inclusion required a confirmed ALS or a mimic diagnosis. Comparative groups included age-matched patients with MRIs performed for non-motor neuron symptoms that were reported as normal or demonstrated leukoaraiosis. Quantitative susceptibility values were compared with ANOVA and Tukey-Kramer (post-hoc). ROC analysis and Youden's index were used to identify optimal cutoff values.


      Fifty ALS, 35 mimic, and 70 non-motor neuron symptom patients (35 normal, 35 leukoaraiosis) were included. Hand and face homunculus mean susceptibility values were significantly higher in the ALS group compared to the mimic (p=0.001, p=0.004), leukoaraiosis (p<0.001, p=0.003), and normal (p<0.001, p<0.001) groups. ROC curve analysis comparing ALS to mimics resulted in an area under the curve of 0.71 and 0.67 for the hand and face homunculus measurements, respectively. In differentiating ALS from mimics, Youden's index showed 100% specificity and 36% sensitivity for hand homunculus measurements.


      QSM has diagnostic potential in the assessment of suspected ALS patients, demonstrating very high specificity in differentiating ALS from mimic diagnoses.


      ALS (Amyotrophic lateral sclerosis), QSM (quantitative susceptibility mapping), PLS (primary lateral sclerosis), ROC (receiver operating characteristic), MND (motor neuron disease), ROI (region on interest), ANOVA (analysis of variance), DICOM (Digital Imaging and Communications in Medicine), PPB (parts per billion), RS (relative susceptibility), UMN (upper motor neuron)


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