Diffusion-time dependent diffusion MRI: effect of diffusion-time on microstructural mapping and prediction of prognostic features in breast cancer

Objectives This study aimed to evaluate the effect of achievable t d on the accuracy of microstructural mapping based on simulation and patient experiments, and investigate the feasibility of t d -dMRI in distinguishing prognostic factors in breast cancer patients. Methods Simulation was performed using different t d settings. Patients with breast cancer were enrolled prospectively between November 2020 and January 2021, who underwent oscillating and pulsed gradient encoded dMRI on a 3-T scanner using short-/long- t d protocol with oscillating frequency up to 50/33 Hz. Data were fitted with a two-compartment model to estimate cell diameter ( d ), intracellular fraction ( f in ), and diffusivities. Estimated microstructural markers were used to differentiate immunohistochemical receptor status and the presence of lymph node (LN), which were correlated with histopathological measurements. Results Simulation results showed that d fitted from the short- t d protocol significantly reduced estimation error than those from long- t d (2.07 ± 1.51% versus 3.05 ± 1.92%, p < 0.0001) while the estimation error of f in was robust to different protocols. Among a total of 37 breast cancer patients, the estimated d was significantly higher in HER2-positive and LN-positive ( p < 0.05) groups compared to their negative counterparts only using the short- t d protocol. Histopathological validation in a subset of 6 patients with whole slide images showed the estimated d was highly correlated with measurements from H&E staining ( r = 0.84, p = 0.03) only using the short- t d protocol. Conclusions The results indicated the necessity of short- t d for accurate microstructural mapping in breast cancer. The current t d -dMRI with a total acquisition time of 4.5 min showed its potential in the diagnosis of breast cancer. Key Points • Short t d is important for accurate microstructural mapping in breast cancer using the t d -dMRI technique, based on simulation and histological validation. • The 4.5-min t d -dMRI protocol showed potential clinical value for breast cancer, given the difference in cell diameter between HER2/LN positive and negative groups.