Disentangling Normal Aging From Severity of Disease via Weak Supervision on Longitudinal MRI.

The continuous progression of neurological diseases are often categorized into conditions according to their severity. To relate the severity to changes in brain morphometry, there is a growing interest in replacing these categories with a continuous severity scale that longitudinal MRIs are mapped onto via deep learning algorithms. However, existing methods based on supervised learning require large numbers of samples and those that do not, such as self-supervised models, fail to clearly separate the disease effect from normal aging. Here, we propose to explicitly disentangle those two factors via weak-supervision. In other words, training is based on longitudinal MRIs being labelled either normal or diseased so that the training data can be augmented with samples from disease categories that are not of primary interest to the analysis. We do so by encouraging trajectories of controls to be fully encoded by the direction associated with brain aging. Furthermore, an orthogonal direction linked to disease severity captures the residual component from normal aging in the diseased cohort. Hence, the proposed method quantifies disease severity and its progression speed in individuals without knowing their condition. We apply the proposed method on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N =632 ). We then show that the model properly disentangled normal aging from the severity of cognitive impairment by plotting the resulting disentangled factors of each subject and generating simulated MRIs for a given chronological age and condition. Moreover, our representation obtains higher balanced accuracy when used for two downstream classification tasks compared to other pre-training approaches. The code for our weak-supervised approach is available at https://github.com/ouyangjiahong/longitudinal-direction-disentangle.