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

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.

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, $$ , and diffusional kurtosis, $$ . Additionally, the Kärger model was used to estimate cellular-interstitial water exchange time ( $$ ) from $$ .

Diffusivity measured by time-dependent STEAM-EPI measurements and commercial SE-EPI showed comparable results with R² above 0.98 and overall 5.4 ± 3.0% deviation across diffusion times. Diffusional kurtosis phantom data showed expected patterns: constant $$ and $$  = 0 for negative controls and slow varying $$ and $$ for samples made of nanoscopic vesicles. Time-dependent diffusion MRI in patients with head and neck cancer found that the Kärger 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.

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 Kärger model for the metastatic lymph nodes in patients with head and neck cancer.