Deep Learning in neuroimaging for neurodegenerative diseases: State-of-the art, Challenges, and Opportunities

Taymaz Akan, Sara Akan, Sait Alp, Christina Raye Ledbetter, Ahmad P. Tafti, Octavio Arevalo, Mohammad Alfrad Nobel Bhuiyan,
Deep Learning in neuroimaging for neurodegenerative diseases: State-of-the art, Challenges, and Opportunities,
Journal of the Neurological Sciences,
Volume 478,
2025,
123735,
ISSN 0022-510X,
https://doi.org/10.1016/j.jns.2025.123735.
(https://www.sciencedirect.com/science/article/pii/S0022510X25003557)
Abstract: Neuroimaging is commonly used to diagnose neurodegenerative diseases (NDDs), providing crucial insights into brain changes before clinical symptoms manifest. Deep learning (DL) for neuroimaging can improve early diagnosis and disease monitoring. Clinical implementation of DL faces challenges in accurately representing real-world data. Recent models, particularly those focused on diagnostic categorization, have achieved high accuracy, but their applicability to patients is limited. Conflicting inferences have been reported, with findings from small cohorts generalizing conclusions without considering inter-scanner, intra- and inter-site variations. A theoretically feasible method involves gathering a comprehensive dataset that encompasses all patient demographics, but this presents practical challenges including harmonization, data incompleteness, class imbalance, and substantial costs. Existing research has also mostly focused on common NDDs like Alzheimer's Disease (AD) and Parkinson's Disease (PD). This contribution expands the literature by looking at a wider range of NDDs, exploring the latest advancements in applying deep learning algorithms to neuroimaging analysis for the diagnosis and monitoring of NDDs, including AD, Frontotemporal Dementia (FTD), Lewy Body Dementia, PD, Huntington's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. We emphasize how these approaches are handling spatial/temporal information available in brain volume imaging data. We conclude by discussing the challenges associated with the use of voxel-based, patch-based, ROI-based, and slice-based approaches in brain volume imaging. These challenges are further compounded by issues such as inter-site and inter-scanner variability, class imbalances in medical datasets, and the scarcity of accurately annotated data, all of which impact the performance and generalizability of deep learning models.
Keywords: Deep learning; Neurodegenerative diseases; Brain disorders; Brain volume; 3D brain scans; CNN; Transformers; Neuroimaging modalities; Early diagnosis