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We investigated the associations of time-dependent DWI, non-Gaussian DWI, and CEST parameters with histological biomarkers in a breast cancer xenograft model. 22 xenograft mice (7 MCF-7 and 15 MDA-MB-231) were scanned at 4 diffusion times [T d  = 2.5/5 ms with 11 b-values (0–600 s/mm 2 ) and T d  = 9/27.6 ms with 17 b-values (0–3000 s/mm 2 ), respectively]. The apparent diffusion coefficient (ADC) was estimated using 2 b-values in different combinations (ADC 0–600  using b = 0 and 600 s/mm 2  and shifted ADC [sADC 200–1500 ] using b = 200 and 1500 s/mm 2 ) at each of those diffusion times. Then the change (Δ) in ADC/sADC between diffusion times was evaluated. Non-Gaussian diffusion and intravoxel incoherent motion (IVIM) parameters (ADC 0 , the virtual ADC at b = 0; K, Kurtosis from non-Gaussian diffusion;  f , the IVIM perfusion fraction) were estimated. CEST images were acquired and the amide proton transfer signal intensity (APT SI) were measured. The ΔsADC 9–27.6  (between    $${\text{sADC}}_{{9\,{\text{ms}}}}^{200{-}1500}$$  sADC 9 ms 200 - 1500 and    $${\text{sADC}}_{{27.6\,{\text{ms}}}}^{200{-}1500}$$  sADC 27.6 ms 200 - 1500 and ΔADC 2.5 _sADC 27.6  (between    $${\text{ADC}}_{{2.5\, {\text{ms}}}}^{0{-}600}$$  ADC 2.5 ms 0 - 600 and    $${\text{sADC}}_{{27.6\,{\text{ms}}}}^{200{-}1500}$$  sADC 27.6 ms 200 - 1500 ) was significantly larger for MCF-7 groups, and ΔADC 2.5 _sADC 27.6  was positively correlated with Ki67 max  and APT SI. ADC 0  decreased significantly in MDA-MB-231 group and K increased significantly with T d  in MCF-7 group. APT SI and cellular area had a moderately strong positive correlation in MDA-MB-231 and MCF-7 tumors combined, and there was a positive correlation in MDA-MB-231 tumors. There was a significant negative correlation between APT SI and the Ki-67-positive ratio in MDA-MB-231 tumors and when combined with MCF-7 tumors. The associations of ΔADC 2.5 _sADC 27.6  and API SI with Ki-67 parameters indicate that the T d -dependent DW and CEST parameters are useful to predict the histological markers of breast cancers.

Investigation of breast cancer microstructure and microvasculature from time-dependent DWI and CEST in correlation with histological biomarkers