CASL-VAE: Learning Structured Latent Variables from Unpaired Data for Semi-supervised Clustering and Paired Sample Generation

Authors: Sai Spandana Chintapalli, Pratik Chaudhari, Christos Davatzikos

Abstract: Quantifying variability in a target population relative to a reference population is central to many scientific and clinical problems (e.g., diseased vs. healthy). Yet, without paired data and in the presence of heterogeneous target variation, existing methods struggle to separate multiple modes of target-specific variation. We propose \textit{CASL-VAE}, a deep contrastive latent variable model th… ▽ More Quantifying variability in a target population relative to a reference population is central to many scientific and clinical problems (e.g., diseased vs. healthy). Yet, without paired data and in the presence of heterogeneous target variation, existing methods struggle to separate multiple modes of target-specific variation. We propose \textit{CASL-VAE}, a deep contrastive latent variable model that learns structured latent generative factors from unpaired data. CASL-VAE factorizes variation into continuous common latent factors shared across populations and hierarchical salient latent factors that model target-specific heterogeneity as discrete subtypes and continuous within-subtype variation. Using variational inference, we show how approximate joint likelihood optimization over reference and target domains can be performed using unpaired data, providing a principled basis for paired-sample generation and cross-domain analysis. We validate CASL-VAE on semi-synthetic neuroimaging data, demonstrating improved subtype recovery and paired-sample generation compared to baseline clustering and generative models. We also validate its ability to reveal biologically plausible heterogeneity in Alzheimer's disease. △ Less

Submitted 9 July, 2026; originally announced July 2026.

Applications of Generative Adversarial Networks in Neuroimaging and Clinical Neuroscience

Authors: Rongguang Wang, Vishnu Bashyam, Zhijian Yang, Fanyang Yu, Vasiliki Tassopoulou, Sai Spandana Chintapalli, Ioanna Skampardoni, Lasya P. Sreepada, Dushyant Sahoo, Konstantina Nikita, Ahmed Abdulkadir, Junhao Wen, Christos Davatzikos

Abstract: Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to a broader family called generative methods, which generate new data with a probabilistic model by learning sample distribution from real examples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, n… ▽ More Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to a broader family called generative methods, which generate new data with a probabilistic model by learning sample distribution from real examples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases. △ Less

Submitted 29 January, 2023; v1 submitted 14 June, 2022; originally announced June 2022.