Neurite orientation dispersion and density imaging in stroke: current applications, limitations, and future...

Stroke is currently one of the leading causes of death and disability worldwide among neurological diseases. Although traditional imaging techniques can clearly delineate lesion extent and hemorrhagic patterns, they are limited in quantifying microscopic structural changes and repair processes in early-stage brain tissue damage. Neurite Orientation Dispersion and Density Imaging (NODDI), an advanced diffusion-weighted MRI technique, enables accurate, non-invasive quantification of post-stroke microstructural changes in brain tissue. NODDI objectively quantifies neurite damage and remodeling, providing crucial imaging evidence for stroke severity, prognosis, and rehabilitation outcome evaluation. This review critically synthesizes NODDI's biophysical principles, evaluates its expanding applications in both ischemic and hemorrhagic stroke-highlighting recent advancements in modeling and clinical translation-discusses persistent limitations, and proposes a roadmap for future research to maximize its clinical utility and address current challenges. Importantly, this review focuses exclusively on magnetic resonance imaging (MRI)-based techniques and does not cover non-MRI modalities such as computed tomography (CT) or positron emission tomography (PET). Notably, post-stroke depression (PSD) affects approximately one-third of stroke survivors and represents a major neuropsychiatric complication that impedes functional recovery and reduces quality of life. Emerging evidence demonstrates that NODDI-derived metrics-particularly ODI and ISO-can identify microstructural disruptions in emotion-related white matter pathways that are specific to PSD, offering potential neuroimaging biomarkers that surpass conventional DTI parameters. These findings position NODDI as a promising tool not only for stroke characterization but also for bridging the gap between focal brain injury and subsequent psychiatric manifestations.