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

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 [Td = 2.5/5 ms with 11 b-values (0–600 s/mm2) and Td = 9/27.6 ms with 17 b-values (0–3000 s/mm2), respectively]. The apparent diffusion coefficient (ADC) was estimated using 2 b-values in different combinations (ADC0–600 using b = 0 and 600 s/mm2 and shifted ADC [sADC200–1500] using b = 200 and 1500 s/mm2) 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 (ADC0, 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 ΔsADC9–27.6 (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 ΔADC2.5_sADC27.6 (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 ΔADC2.5_sADC27.6 was positively correlated with Ki67max and APT SI. ADC0 decreased significantly in MDA-MB-231 group and K increased significantly with Td 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 ΔADC2.5_sADC27.6 and API SI with Ki-67 parameters indicate that the Td-dependent DW and CEST parameters are useful to predict the histological markers of breast cancers.

Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer

“…4T1 tumors exhibited increasing intratumoral hemorrhage due to vascular leakiness over time, while 67NR tumors were largely homogenous. However, the observed changes in MRI might be similar to the changes in certain pathological features, as assessment of the changes in diffusion-weighted imaging has already been found to correlate with the Ki67 proliferation status in a mouse model of rhabdomyosarcoma ( 61 ) and has been found useful to predict histological markers such as Ki67 in the breast cancer xenografts MCF-7 and MDA-MB-231 ( 62 ). Although only visually assessed in this study, 4T1 tumors exhibited a higher Ki67 proliferation status overall, with an increase over time and 67NR tumors had a lower Ki67 index overall and a decrease over time, which was also found in the p90 histogram analysis.…”

<i>In Vivo</i> and <i>Post-mortem</i> Comparisons of IVIM/Time-dependent Diffusion MR Imaging Parameters in Melanoma and Breast Cancer Xenograft Models

“…We previously reported that the decrease in ADC values with longer diffusion time could suggest the presence of hindered/restricted diffusion. [18][19][20] Under free diffusion, the root-mean-square of water molecule displacement is known to be proportional to the root of diffusion time (the diffusion coefficient is constant, regardless of diffusion time). However, under hindered/restricted diffusion, the probability of water molecules hitting obstacles increases with longer measurement time.…”

Advanced Magnetic Resonance Imaging Modalities for Breast Cancer Diagnosis: An Overview of Recent Findings and Perspectives

“…A study on the application of APTWI to assess breast lesions recently commenced. While several research findings have evaluated the utility of APTWI in tumor grading, cell proliferation [ 85 ], and its importance in treatment-related lymphedema therapy [ 86 ], few studies have examined APTWI’s effectiveness in diagnosing benign and malignant lesions and the connection among its parameters and prognostic factors [ 87 ]. Meng et al attempted to evaluate the roles of diffusion kurtosis imaging (DKI) and APTWI in distinguishing benign and malignant breast lesions and examine the correlation coefficients between the obtained parameters and breast cancer prognostic factors to develop novel concepts for breast cancer diagnosis, treatment, and prognostic assessment.…”