Time-dependent diffusivity and kurtosis in phantoms and patients with head and neck cancer

Purpose To assess the reliability of measuring diffusivity, diffusional kurtosis, and cellular-interstitial water exchange time with long diffusion times (100-800 ms) using stimulated-echo DWI. Methods Time-dependent diffusion MRI was tested on two well-established diffusion phantoms and in 5 patients with head and neck cancer. Measurements were conducted using an in-house diffusion-weighted STEAM-EPI pulse sequence with multiple diffusion times at a fixed TE on three scanners. We used the weighted linear least-squares fit method to estimate time-dependent diffusivity, D(t)$$ D(t) $$, and diffusional kurtosis, K(t)$$ K(t) $$. Additionally, the Karger model was used to estimate cellular-interstitial water exchange time (tau ex$$ {\tau}_{ex} $$) from K(t)$$ K(t) $$. Results Diffusivity measured by time-dependent STEAM-EPI measurements and commercial SE-EPI showed comparable results with R-2 above 0.98 and overall 5.4 +/- 3.0% deviation across diffusion times. Diffusional kurtosis phantom data showed expected patterns: constant D$$ D $$ and K$$ K $$ = 0 for negative controls and slow varying D$$ D $$ and K$$ K $$ for samples made of nanoscopic vesicles. Time-dependent diffusion MRI in patients with head and neck cancer found that the Karger model could be considered valid in 72% +/- 23% of the voxels in the metastatic lymph nodes. The median cellular-interstitial water exchange time estimated for lesions was between 58.5 ms and 70.6 ms. Conclusions Based on two well-established diffusion phantoms, we found that time-dependent diffusion MRI measurements can provide stable diffusion and kurtosis values over a wide range of diffusion times and across multiple MRI systems. Moreover, estimation of cellular-interstitial water exchange time can be achieved using the Karger model for the metastatic lymph nodes in patients with head and neck cancer.