ReMiND: Recovery of Missing Neuroimaging using Diffusion Models with Application to Alzheimer’s Disease

OBJECTIVE: Missing data is a significant challenge in medical research. In longitudinal studies of Alzheimer’s disease (AD) where structural magnetic resonance imaging (MRI) is collected from individuals at multiple time points, participants may miss a study visit or drop out. Additionally, technical issues such as participant motion in the scanner may result in unusable imaging data at designated visits. Such missing data may hinder the development of high-quality imaging-based biomarkers. Furthermore, when imaging data are unavailable in clinical practice, patients may not benefit from effective application of biomarkers for disease diagnosis and monitoring. METHODS: To address the problem of missing MRI data in studies of AD, we introduced a novel 3D diffusion model specifically designed for imputing missing structural MRI (Recovery of Missing Neuroimaging using Diffusion models (ReMiND)). The model generates a whole-brain image conditional on a single structural MRI observed at a past visit or conditional on one past and one future observed structural MRI relative to the missing observation. RESULTS: Experimental results show that our method can generate high-quality individual 3D structural MRI with high similarity to ground truth, observed images. Additionally, images generated using ReMiND exhibit relatively lower error rates and more accurately estimated rates of atrophy over time in important anatomical brain regions compared with two alternative imputation approaches: forward filling and image generation using variational autoencoders. CONCLUSION: Our 3D diffusion model can impute missing structural MRI data at a single designated visit and outperforms alternative methods for imputing whole-brain images that are missing from longitudinal trajectories.