Time-dependent diffusion magnetic resonance imaging: principles, acquisition sequences, main models, current applications, and future directions

Time-dependent diffusion magnetic resonance imaging (TDDMRI) has emerged as a prominent technique for probing the microstructure of biological tissues. By varying diffusion time and exploiting the time dependence of restricted water diffusion, TDDMRI enables noninvasive inference and mapping of tissue microstructure. This technology is expanding its applications in disease research. In this article, we review the technique's physical principles, primary diffusion encoding sequences, and widely adopted biophysical models. Beyond this, we systematically examine its specific applications in clinical diseases: spanning intracranial, cervical, thoracic, abdominopelvic tumors, and skeletal muscle-related diseases, we detail its superiority over conventional imaging modalities-notably its high diagnostic value for malignant tumor detection and characterization. Finally, we identify current limitations in clinical translation and potential directions for future technical development.