The Rate of Apparent Diffusion Coefficient Change With Diffusion Time on Breast Diffusion-Weighted Imaging Depends on Breast Tumor Types and Molecular Prognostic Biomarker Expression

Abstract

Introduction:The aim of this study was to investigate the variation of apparent diffusion coefficient (ADC) values with diffusion time according to breast tumor type and prognostic biomarkers expression. Materials and Methods: A total of 201 patients with known or suspected breast tumors were prospectively enrolled in this study, and 132 breast tumors (86 malignant and 46 benign) were analyzed. Diffusion-weighted imaging scans with 2 diffusion times were acquired on a clinical 3-T magnetic resonance imaging scanner using oscillating and pulsed diffusion-encoding gradients (effective diffusion times, 4.7 and 96.6 milliseconds) and b values of 0 and 700 s/mm 2 . Diagnostic performances to differentiate malignant and benign breast tumors for ADC values at short and long diffusion times (ADC short and ADC long ), ΔADC (the rate of change in ADC values with diffusion time), ADC 0-1000 (ADC value from a standard protocol), and standard reading including dynamic contrast-enhanced magnetic resonance imaging (BI-RADS) were investigated. The correlations of ADC short , ADC long , and ΔADC values with hormone receptor expression and breast cancer subtypes were also analyzed. Results:The ADC values were lower, and ΔADC was higher in malignant tumors compared with benign tumors. The specificity of ADC values at all diffusion times and ΔADC values for differentiating malignant and benign breast tumors was superior to that of BI-RADS (87.0%-95.7% vs 73.9%), whereas the sensitivity was inferior (87.2%-90.7% vs 100%). Lower ADC short and ADC 0-1000 in ER-positive compared with ER-negative cancers (false discovery rate [FDR]-adjusted P = 0.037 and 0.018, respectively) and lower ADC short , ADC long , and ADC 0-1000 in progesterone receptor-positive compared with progesterone receptor-negative cancers (FDR-adjusted P = 0.037, 0.036, and 0.018, respectively) were found. Ki-67-positive cancers had larger ΔADCs than Ki-67-negative cancers (FDR-adjusted P = 0.018). Conclusions:The ADC values vary with different diffusion time and vary in correlation with molecular biomarkers, especially Ki-67. Those results suggest that the diffusion time, which should be reported, might be a useful parameter to consider for breast cancer management.

Investigation of Breast Cancer Microstructure and Microvasculature from Time-Dependent DWI and CEST in Correlation with Histological Biomarkers

“…The observed decrease in ADC and sADC values with T d in breast tumors was in agreement with the literature, as were the results of our previous investigation 11,32,42 . This con rms the hypothesis that diffusion hindrance in tumors increases when the T d value increases, as more molecules might hit the increased number of obstacles such as cell membranes.…”

“…A previous study that compared between benign and malignant tumors revealed greater ADC change in malignant than benign lesions 32,42 . In this study, we assumed that more malignant pathological features like active proliferation, tight structure, and small cell spacing hinder the diffusion of water molecules inside tissue and ultimately decrease the ADC value in MDA-MB-231 tumors.…”

“…We found that the combined ADC change using different T d values had a signi cant positive correlation with APT SI. Previous studies have reported that time-dependent DWI or CEST imaging might provide information about tumor microstructure indicating tumor proliferation in oncologic imaging [28][29][30][31][32] . Comparisons of APT SI and IVIM parameters in cervical cancers 33 , gliomas 34 , and hepatocellular carcinomas 35 , as well as comparisons of APT SI and diffusion kurtosis imaging in rectal carcinomas 36 , have been reported.…”

“…Indeed, although the T d settings available on clinical MRI scanners used to be similar, the availability of new, stronger gradient hardware now allows access to a broad range of T d values while maintaining high b values. In general, the previous studies implicated that the ADC values obtained at very short T d might diminish the contrast for differentiation between lesion types (i.e., malignant vs. benign lesions) because of a reduced sensitivity to diffusion hindrance 11,32 tissue structure, such as cell size, cell density, or cell membranes 44 .…”

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

“…We found that the ΔADC 2.5 _sADC 27.6 using different T d values had a significant positive correlation with APT SI. Previous studies have reported that time-dependent DWI or CEST imaging might provide information about tumor microstructure indicating tumor proliferation in oncologic imaging 29 – 33 . Comparisons of APT SI and IVIM parameters in cervical cancers 34 , gliomas 35 , and hepatocellular carcinomas 36 , as well as comparisons of APT SI and diffusion kurtosis imaging in rectal carcinomas 37 , have been reported.…”