Microstructural mapping with time-dependent diffusion MRI: From OGSE sequence to clinical translation

Tumorous lesions and neurological disorders are major causes of disability and death worldwide. Evaluating alterations in the microstructural characteristics of tumor cells and the damage to small axons in neurological diseases has become an emerging area of research. Time-Dependent Diffusion magnetic resonance imaging (TDD-MRI) is one of the most promising techniques for imaging tissue microstructure, with remarkable progress achieved in both tumor and neuroimaging studies. Traditional TDD-MRI typically employs pulsed gradient spin-echo (PGSE) sequences, which probe relatively long diffusion times. In contrast, oscillating gradient spin-echo (OGSE) sequences probe diffusion over shorter effective timescales by modulating the oscillation frequency of the diffusion gradients, rather than varying the diffusion interval as in PGSE. This approach enables the detection of faster diffusion processes and improves sensitivity to the restrictive effects of cell membranes on the Brownian motion of water molecules, thereby providing more detailed insights into tissue microstructure. OGSE can probe diffusion dynamics on short timescales (≤10 ms), offering sensitivity to microscopic tissue features on the order of ≤10 μm. OGSE-based microstructural imaging techniques have been established in preclinical studies to characterize cell size and cellular density. The unique contrast provided by OGSE has shown potential in distinguishing tumor types and grades, enabling early assessment of therapeutic responses, and revealing neurological disorders. This review focuses on the technical principles and clinical applications of TDD-MRI, highlighting its potential to bridge the gap between microstructural characterization and clinical diagnosis.