Toward MR protocol-agnostic, bias-corrected brain age predicted from clinical-grade MRIs

The predicted brain age minus the chronological age ('brain-PAD') could become a clinical biomarker. However, most brain age methods were developed to use research-grade high-resolution T1-weighted MRIs, limiting their applicability to clinical-grade MRIs from multiple protocols. To overcome this, we adopted a double transfer learning approach to develop a brain age model agnostic to modality, resolution, or slice orientation. Using 6,224 clinical MRIs among 7 modalities, scanned from 1,540 patients using 8 scanners among 15 + facilities of the University of Florida's Health System, we retrained a convolutional neural network (CNN) to predict brain age from synthetic research-grade magnetization-prepared rapid gradient-echo MRIs (MPRAGEs) generated by a deep learning-trained 'super-resolution' method. We also modeled the "regression dilution bias", a typical overestimation of younger ages and underestimation of older ages, which correction is paramount for personalized brain age-based biomarkers. This bias was independent of modality or scanner and generalizable to new samples, allowing us to add a bias-correction layer to the CNN. The mean absolute error in test samples was 4.67-6.47 years across modalities, with similar accuracy between original MPRAGEs and their synthetic counterparts. Brain-PAD was also reliable across modalities. We demonstrate the feasibility of clinical-grade brain age predictions, contributing to personalized medicine.