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 ( τ 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 τ 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 τ 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 τ 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.