DCE-MRI quantitative transport mapping for noninvasively detecting hypoxia inducible factor-1α, epidermal growth factor receptor overexpression, and Ki-67 in nasopharyngeal carcinoma patients.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to noninvasively detect expression of hypoxia inducible factor-1-alpha (HIF-1α), epidermal growth factor receptor (EGFR), and Ki-67 in nasopharyngeal carcinoma (NPC) by quantitatively measuring tumor blood flow, vascularity, and permeability. PURPOSE: We aim to explore the utility of DCE-MRI in detecting HIF-1α, EGFR, and Ki-67 expression levels using traditional Kety's/Tofts' modeling and quantitative transport mapping (QTM). MATERIALS AND METHODS: Eighty-nine NPC patients underwent DCE-MRI before treatment were enrolled. DCE-MRI was processed to generate the following kinetic parameters: |u| and D from the QTM model, tumor blood flow (TBF) from Kety's model, and Ktrans, Ve, and Kep from Tofts' model. Pretreatment levels of HIF-1α, EGFR, and Ki-67 were assessed by immunohistochemistry and classified into low and high expression groups. RESULTS: |u| (p < 0.001) and TBF (p = 0.015) values were significantly higher in the HIF-1α high-expression group compared to low-expression group. Only Ktrans (p = 0.016) was significantly higher in the EGFR high-expression group. Only |u| (p < 0.001) values were significantly higher in the Ki-67 high-expression group compared to low-expression group. Multiple linear regression analyses showed that |u| independently correlated with HIF-1α and Ki-67 expression, and Ktrans independently correlated with EGFR. The areas under the ROC curves of |u| for HIF-1α and Ki-67, and Ktrans for EGFR were 0.83, 0.74, and 0.70, respectively. CONCLUSION: |u| and Ktrans derived from DCE-MRI may be considered as noninvasive imaging markers for detecting hypoxia and proliferation in NPC patients.

Multicenter reproducibility of quantitative susceptibility mapping in a gadolinium phantom using MEDI+0 automatic zero referencing.

PURPOSE: To determine the reproducibility of quantitative susceptibility mapping at multiple sites on clinical and preclinical scanners (1.5 T, 3 T, 7 T, and 9.4 T) from different vendors (Siemens, GE, Philips, and Bruker) for standardization of multicenter studies. METHODS: Seven phantoms distributed from the core site, each containing 5 compartments with gadolinium solutions with fixed concentrations between 0.625 mM and 10 mM. Multi-echo gradient echo scans were performed at 1.5 T, 3 T, 7 T, and 9.4 T on 12 clinical and 3 preclinical scanners. DICOM images from the scans were processed into quantitative susceptibility maps using the Laplacian boundary value (LBV) and MEDI+0 automatic uniform reference algorithm. Region of interest (ROI) analyses were performed by a physicist to determine agreement between results from all sites. Measurement reproducibility was assessed using regression, Bland-Altman plots, and the intra-class correlation coefficient (ICC). RESULTS: Quantitative susceptibility mapping (QSM) from all scanners had similar, artifact-free visual appearance. Regression analysis showed a linear relationship between gadolinium concentrations and average QSM measurements for all phantoms (y = 350x - 0.0346, r2 >0.99). The SD of measurements increased almost linearly from 32 ppb to 230 ppb as the measured susceptibility increased from 0.26 ppm to 3.56 ppm. A Bland-Altman plot showed the bias, upper, and lower limits of agreement for all comparisons were -10, -210, and 200 ppb, respectively. The ICC was 0.991 with a 95% CI (0.973, 0.99). CONCLUSIONS: QSM shows excellent multicenter reproducibility for a large range of susceptibility values encountered in cranial and extra-cranial applications on a diverse set of scanner platforms.