A Skewed Loss Function for Correcting Predictive Bias in Brain Age Prediction.

In neuroimaging, the difference between predicted brain age and chronological age, known as brain age delta, has shown its potential as a biomarker related to various pathological phenotypes. There is a frequently observed bias when estimating brain age delta using regression models. This bias manifests as an overestimation of brain age for young participants and an underestimation of brain age for older participants. Therefore, the brain age delta is negatively correlated with chronological age, which can be problematic when evaluating relationships between brain age delta and other age-associated variables. This paper proposes a novel bias correction method for regression models by introducing a skewed loss function to replace the normal symmetric loss function. The regression model then behaves differently depending on whether it makes overestimations or underestimations. Our approach works with any type of MR image and no specific preprocessing is required, as long as the image is sensitive to age-related changes. The proposed approach has been validated using three classic deep learning models, namely ResNet, VGG, and GoogleNet on publicly available neuroimaging aging datasets. It shows flexibility across different model architectures and different choices of hyperparameters. The corrected brain age delta from our approach then has no linear relationship with chronological age and achieves higher predictive accuracy than a commonly-used two-stage approach.