AUTHOR=Ganzetti Marco , Valsasina Paola , Barkhof Frederik , Rocca Maria A. , Filippi Massimo , Prados Ferran , Craveiro Licinio TITLE=SynSpine: an automated workflow for the generation of longitudinal spinal cord synthetic MRI data JOURNAL=Frontiers in Neuroinformatics VOLUME=Volume 19 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/neuroinformatics/articles/10.3389/fninf.2025.1649440 DOI=10.3389/fninf.2025.1649440 ISSN=1662-5196 ABSTRACT=BackgroundSpinal cord atrophy is a key biomarker for tracking disease progression in neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and spinal cord injury. Recent MRI advancements have improved atrophy detection, particularly in the cervical region, facilitating longitudinal studies. However, validating atrophy quantification algorithms remains challenging due to limited ground truth data.ObjectiveThis study introduces SynSpine, a workflow for generating synthetic spinal cord MRI data (i.e., digital phantoms) with controlled levels of artificial atrophy. These phantoms support the development and preliminary validation of spinal cord imaging pipelines designed to measure degeneration over time.MethodsThe workflow consists of two phases: (1) generating synthetic MR images by isolating, extracting and scaling the spinal cord, simulating atrophy on the PAM50 template; (2) performing non-rigid registration to align the synthetic images with the subject’s native space, ensuring accurate anatomical correspondence. A proof-of-concept application utilizing the Active Surface and Reg methods implemented in Jim demonstrated its effectiveness in detecting atrophy across various levels of simulated atrophy and noise.ResultsSynSpine successfully generates synthetic spinal cord images with varying atrophy levels. Non-rigid registration did not significantly affect atrophy measurements. Atrophy estimation errors, estimated using Active Surface and Reg methods, varied with both simulated atrophy magnitude and noise level, exhibiting region-dependent differences. Increased noise led to higher measurement errors.ConclusionThis work presents a novel and modular framework for simulating spinal cord atrophy data using digital phantoms, offering a controlled setting for testing spinal cord analysis pipelines. As the simulated atrophy may over-simplify in vivo conditions, future research will focus on enhancing the realism of the synthetic dataset by simulating additional pathologies, thus improving its application for evaluating spinal cord atrophy in clinical and research contexts.