Longitudinal Causal Image Synthesis

Clinical decision-making relies heavily on causal reasoning and longitudinal analysis. For example, for a patient with Alzheimer's disease (AD), how will the brain grey matter atrophy in a year if intervened on the A-beta level in cerebrospinal fluid? The answer is fundamental to diagnosis and follow-up treatment. However, this kind of inquiry involves counterfactual medical images which can not be acquired by instrumental or correlation-based image synthesis models. Yet, such queries require counterfactual medical images, not obtainable through standard image synthesis models. Hence, a causal longitudinal image synthesis (CLIS) method, enabling the synthesis of such images, is highly valuable. However, building a CLIS model confronts three primary yet unmet challenges: mismatched dimensionality between high-dimensional images and low-dimensional tabular variables, inconsistent collection intervals of follow-up data, and inadequate causal modeling capability of existing causal graph methods for image data. In this paper, we established a tabular-visual causal graph (TVCG) for CLIS overcoming these challenges through a novel integration of generative imaging, continuous-time modeling, and structural causal models combined with a neural network. We train our CLIS based on the ADNI dataset and evaluate it on two other AD datasets, which illustrate the outstanding yet controllable quality of the synthesized images and the contributions of synthesized MRI to the characterization of AD progression, substantiating the reliability and utility in clinics.