Measurement of cellular-interstitial water exchange time in tumors based on diffusion-time-dependent diffusional kurtosis imaging

Purpose To assess the feasibility of using diffusion-time-dependent diffusional kurtosis imaging (tDKI) to measure cellular-interstitial water exchange time (tau(ex)) in tumors, both in animals and in humans. Methods Preclinical tDKI studies at 7 T were performed with the GL261 glioma model and the 4T1 mammary tumor model injected into the mouse brain. Clinical studies were performed at 3 T with women who had biopsy-proven invasive ductal carcinoma. tDKI measurement was conducted using a diffusion-weighted STEAM pulse sequence with multiple diffusion times (20-800 ms) at a fixed echo time, while keeping the b-values the same (0-3000 s/mm(2)) by adjusting the diffusion gradient strength. The tDKI data at each diffusion time t were used for a weighted linear least-squares fit method to estimate the diffusion-time-dependent diffusivity, D(t), and diffusional kurtosis, K(t). Results Both preclinical and clinical studies showed that, when diffusion time t >= 200 ms, D(t) did not have a noticeable change while K(t) decreased monotonically with increasing diffusion time in tumors and t >= 100 ms for the cortical ribbon of the mouse brain. The estimated tau(ex) averaged median and interquartile range (IQR) of GL261 and 4T1 tumors were 93 (IQR = 89) ms and 68 (78) ms, respectively. For the cortical ribbon, the estimated tau(ex) averaged median and IQR were 41 (34) ms for C57BL/6 and 30 (17) ms for BALB/c. For invasive ductal carcinoma, the estimated tau(ex) median and IQR of the two breast cancers were 70 (94) and 106 (92) ms. Conclusion The results of this proof-of-concept study substantiate the feasibility of using tDKI to measure cellular-interstitial water exchange time without using an exogenous contrast agent.

Automated summary

The feasibility of using diffusion-time-dependent diffusional kurtosis imaging (tDKI) to measure cellular-interstitial water exchange time (tau(ex)) in tumors was assessed in both animal and human studies. Both preclinical and clinical studies showed that D(t) did not change significantly when diffusion time t was greater than or equal to 200 ms, while K(t) decreased monotonically with increasing diffusion time.