Extensive evaluation of morphological statistical harmonization for brain age prediction

Characterizing both neurodevelopmental and aging brain structural trajectories is important for understanding normal biological processes and atypical patterns that are related to pathological phenomena. Initiatives to share open access morphological data contributed significantly to the advance in brain structure characterization. Indeed, such initiatives allow large brain morphology multi-site datasets to be shared, which increases the statistical sensitivity of the outcomes. However, using neuroimaging data from multi-site studies requires harmonizing data across the site to avoid bias. In this work we evaluated three different harmonization techniques on the Autism Brain Imaging Data Exchange (ABIDE) dataset for age prediction analysis in two groups of subjects (i.e., controls and autism spectrum disorder). We extracted the morphological features from T1-weighted images of a mixed cohort of 654 subjects acquired from 17 sites to predict the biological age of the subjects using three machine learning regression models. A machine learning framework was developed to quantify the effects of the different harmonization strategies on the final performance of the models and on the set of morphological features that are relevant to the age prediction problem in both the presence and absence of pathology. The results show that, even if two harmonization strategies exhibit similar accuracy of predictive models, a greater mismatch occurs between the sets of most age-related predictive regions for the Autism Spectrum Disorder (ASD) subjects. Thus, we propose to use a stability index to extract meaningful features for a robust clinical validation of the outcomes of multiple harmonization strategies.