A validation study of manual atrophy measures in patients with Multiple Sclerosis

Purpose: Manual measures such as corpus callosum index, normalized corpus callosum area, and width of the third ventricle are potential biomarkers for brain atrophy. In this work, we investigate their suitability to assess the neurodegenerative component of multiple sclerosis (MS) by comparing them to volumetric measures and expanded disability status scale (EDSS). Methods: Fifty-eight patients with a clinically isolated syndrome, 48 MS patients treated with interferon β, and 26 treated with natalizumab underwent a brain MRI at baseline and after 1 year. Manual measures were evaluated by two observers using Jim v.6.0 at both time points. Volumetric tools (SIENA/x and Freesurfer) were used to calculate normalized brain volume, brain parenchymal fraction, annualized percentage of brain volume change, corpus callosum volume, ventricle volume, and volume of the third ventricle. Statistical analyses were performed with SPSS v.13. Results: Usage of corpus callosum volume and third ventricle volume to validate normalized corpus callosum area and width of the third ventricle, respectively, showed very good correlations (r = 0.85, r = 0.83; p < 0.01). Width of the third ventricle, corpus callosum index, and normalized corpus callosum area correlations were significant with EDSS in all patients and moderate to strong with normalized brain volume and brain parenchymal fraction in natalizumab-treated patients (respectively r = − 0.54, r = − 0.61; r = 0.55, r = 0.67; and r = 0.58, r = 0.67; with p < 0.05). Conclusion: Width of the third ventricle and normalized corpus callosum area seem the more robust manual measures regarding correlation with volumetric measures and EDSS, especially in patients with more advanced disease.