Predicting Clinical Variable from MRI Features: Application to MMSE in MCI

The ability to predict a clinical variable from automated analysis of single, cross-sectional T1-weighted (T1w) MR scans stands to improve the management of patients with neurological diseases. We present a methodology for predicting yearly Mini-Mental Score Examination (MMSE) changes in Mild Cognitive Impairment (MCI) patients. We begin by generating a non-pathological, multidimensional reference space from a group of 152 healthy volunteers by Principal Component Analyses of (i) T1w MR intensity of linearly registered Volumes of Interest (VOI); and (ii) trace of the deformation fields of nonlinearly registered VOIs. We use multiple regression to build linear models from eigenvectors where the projection eigencoordinates of patient data in the reference space are highly correlated with the clinical variable of interest. In our cohort of 47 MCI patients, composed of 16 decliners, 26 stable and 5 improvers (based on MMSE at 1 yr follow-up), there was a significant difference (P = 0.0003) for baseline MMSE scores between decliners and improvers, but no other differences based on age or sex. First, we classified our three groups using leave-one-out, forward stepwise linear discriminant analyses of the projection eigencoordinates with 100% accuracy. Next, we compared various linear models by computing F-statistics on the residuals of predicted vs actual values. The best model was based on 10 eigenvectors + baseline MMSE, with predicted yearly changes highly correlated (r = 0.6955) with actual data. Prospective study of an independent cohort of patients is the next logical step towards establishing this promising technique for clinical use.