Explainable Brain Age Prediction using coVariance Neural Networks

In computational neuroscience, there has been an increased interest in developing machine learning algorithms that leverage brain imaging data to provide estimates of "brain age" for an individual. Importantly, the discordance between brain age and chronological age (referred to as "brain age gap") can capture accelerated aging due to adverse health conditions and therefore, can reflect increased vulnerability towards neurological disease or cognitive impairments. However, widespread adoption of brain age for clinical decision support has been hindered due to lack of transparency and methodological justifications in most existing brain age prediction algorithms. In this paper, we leverage coVariance neural networks (VNN) to propose an anatomically interpretable framework for brain age prediction using cortical thickness features. Specifically, our brain age prediction framework extends beyond the coarse metric of brain age gap in Alzheimer's disease (AD) and we make two important observations: (i) VNNs can assign anatomical interpretability to elevated brain age gap in AD by identifying contributing brain regions, (ii) the interpretability offered by VNNs is contingent on their ability to exploit specific eigenvectors of the anatomical covariance matrix. Together, these observations facilitate an explainable perspective to the task of brain age prediction.

Transferability of coVariance Neural Networks and Application to Interpretable Brain Age Prediction using Anatomical Features

Graph convolutional networks (GCN) leverage topology-driven graph convolutional operations to combine information across the graph for inference tasks. In our recent work, we have studied GCNs with covariance matrices as graphs in the form of coVariance neural networks (VNNs) that draw similarities with traditional PCA-driven data analysis approaches while offering significant advantages over them. In this paper, we first focus on theoretically characterizing the transferability of VNNs. The notion of transferability is motivated from the intuitive expectation that learning models could generalize to "compatible" datasets (possibly of different dimensionalities) with minimal effort. VNNs inherit the scale-free data processing architecture from GCNs and here, we show that VNNs exhibit transferability of performance over datasets whose covariance matrices converge to a limit object. Multi-scale neuroimaging datasets enable the study of the brain at multiple scales and hence, can validate the theoretical results on the transferability of VNNs. To gauge the advantages offered by VNNs in neuroimaging data analysis, we focus on the task of "brain age" prediction using cortical thickness features. In clinical neuroscience, there has been an increased interest in machine learning algorithms which provide estimates of "brain age" that deviate from chronological age. We leverage the architecture of VNNs to extend beyond the coarse metric of brain age gap in Alzheimer's disease (AD) and make two important observations: (i) VNNs can assign anatomical interpretability to elevated brain age gap in AD, and (ii) the interpretability offered by VNNs is contingent on their ability to exploit specific principal components of the anatomical covariance matrix. We further leverage the transferability of VNNs to cross validate the above observations across different datasets.