Investigation of breast cancer microstructure and microvasculature from time-dependent DWI and CEST in correlation with histological biomarkers
Yuko Someya, Mami Iima, Hirohiko Imai, Akihiko Yoshizawa, Masako Kataoka, Hiroyoshi Isoda, Denis Le Bihan, Yuji Nakamoto
Abstract
Abstract 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 $${\text{sADC}}_{{9\,{\text{ms}}}}^{200{-}1500}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msubsup> <mml:mtext>sADC</mml:mtext> <mml:mrow> <mml:mrow> <mml:mn>9</mml:mn> <mml:mspace/> <mml:mtext>ms</mml:mtext> </mml:mrow> </mml:mrow> <mml:mrow> <mml:mn>200</mml:mn> <mml:mo>-</mml:mo> <mml:mn>1500</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> and $${\text{sADC}}_{{27.6\,{\text{ms}}}}^{200{-}1500}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msubsup> <mml:mtext>sADC</mml:mtext> <mml:mrow> <mml:mrow> <mml:mn>27.6</mml:mn> <mml:mspace/> <mml:mtext>ms</mml:mtext> </mml:mrow> </mml:mrow> <mml:mrow> <mml:mn>200</mml:mn> <mml:mo>-</mml:mo> <mml:mn>1500</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> and ΔADC 2.5 _sADC 27.6 (between $${\text{ADC}}_{{2.5\, {\text{ms}}}}^{0{-}600}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msubsup> <mml:mtext>ADC</mml:mtext> <mml:mrow> <mml:mrow> <mml:mn>2.5</mml:mn> <mml:mspace/> <mml:mtext>ms</mml:mtext> </mml:mrow> </mml:mrow> <mml:mrow> <mml:mn>0</mml:mn> <mml:mo>-</mml:mo> <mml:mn>600</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> and $${\text{sADC}}_{{27.6\,{\text{ms}}}}^{200{-}1500}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msubsup> <mml:mtext>sADC</mml:mtext> <mml:mrow> <mml:mrow> <mml:mn>27.6</mml:mn> <mml:mspace/> <mml:mtext>ms</mml:mtext> </mml:mrow> </mml:mrow> <mml:mrow> <mml:mn>200</mml:mn> <mml:mo>-</mml:mo> <mml:mn>1500</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> ) 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.