While utilizing machine learning models, one of the most crucial aspects is how bias and fairness affect model outcomes for diverse demographics. This becomes especially relevant in the context of machine learning for medical imaging applications as these models are increasingly being used for diagnosis and treatment planning. In this paper, we study biases related to sex when developing a machine learning model based on brain magnetic resonance images (MRI). We investigate the effects of sex by performing brain age prediction considering different experimental designs: model trained using only female subjects, only male subjects and a balanced dataset. We also perform evaluation on multiple MRI datasets (Calgary-Campinas(CC359) and CamCAN) to assess the generalization capability of the proposed models. We found disparities in the performance of brain age prediction models when trained on distinct sex subgroups and datasets, in both final predictions and decision making (assessed using interpretability models). Our results demonstrated variations in model generalizability across sex-specific subgroups, suggesting potential biases in models trained on unbalanced datasets. This underlines the critical role of careful experimental design in generating fair and reliable outcomes.

Deep learning models have achieved state-of-the-art results in estimating brain age, which is an important brain health biomarker, from magnetic resonance (MR) images. However, most of these models only provide a global age prediction, and rely on techniques, such as saliency maps to interpret their results. These saliency maps highlight regions in the input image that were significant for the model's predictions, but they are hard to be interpreted, and saliency map values are not directly comparable across different samples. In this work, we reframe the age prediction problem from MR images to an image-to-image regression problem where we estimate the brain age for each brain voxel in MR images. We compare voxel-wise age prediction models against global age prediction models and their corresponding saliency maps. The results indicate that voxel-wise age prediction models are more interpretable, since they provide spatial information about the brain aging process, and they benefit from being quantitative.