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Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI.

ABSTRACT: Extracellular pH (pHe) decrease is associated with tumor growth, invasion, metastasis, and chemoresistance, which can be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of the liver cancer microenvironment. In in vitro studies, we firstly explored whether ioversol signal is pH-dependent, and calculated the function equation between the CEST effects of ioversol and pH values, in the range of 6.0 to 7.8, by a ratiometric method. Then we verified the feasibility of this technique and the equation in vivo by applying pHe imaging in an MMTV-Erbb2 transgenic mouse breast cancer model, which is often used in CEST pHe studies. Furthermore, in vivo ioversol CEST MRI, we were able to map relative pHe and differentiate between tumor and normal tissue in a McA-RH7777 rat hepatoma model. This suggests pHe may be a useful biomarker for human liver cancer.

SUBMITTER: Chen M

PROVIDER: S-EPMC5542224 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI.

Chen Miaomiao M Chen Chaoying C Shen Zhiwei Z Zhang Xiaolei X Chen Yanzi Y Lin Fengfeng F Ma Xilun X Zhuang Caiyu C Mao Yifei Y Gan Haochuan H Chen Peidong P Zong Xiaodan X Wu Renhua R

Oncotarget 20170701 28

Extracellular pH (pHe) decrease is associated with tumor growth, invasion, metastasis, and chemoresistance, which can be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of the liver cancer microenvironment. In in vitro studies, we firstly explored whether ioversol signal is pH-dependent, and calculated the function equation between the CEST effects of ioversol and pH va ...[more]

PMID: 28501855

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Project description:PurposeTo quantify chemical exchange saturation transfer contrast in upper extremities of participants with lymphedema before and after standardized lymphatic mobilization therapy using correction procedures for B0 and B1 heterogeneity, and T1 relaxation.MethodsFemales with (n = 12) and without (n = 17) breast cancer treatment-related lymphedema (BCRL) matched for age and body mass index were scanned at 3.0T MRI. B1 efficiency and T1 were calculated in series with chemical exchange saturation transfer in bilateral axilla (B1 amplitude = 2µT, Δω = ±5.5 ppm, slices = 9, spatial resolution = 1.8 × 1.47 × 5.5 mm3 ). B1 dispersion measurements (B1 = 1-3 µT; increment = 0.5 µT) were performed in controls (n = 6 arms in 3 subjects). BCRL participants were scanned pre- and post-manual lymphatic drainage (MLD) therapy. Chemical exchange saturation transfer amide proton transfer (APT) and nuclear Overhauser effect (NOE) metrics corrected for B1 efficiency were calculated, including proton transfer ratio (PTR'), magnetization transfer ratio asymmetry (MTRasymmetry') , and apparent exchange-dependent relaxation (AREX'). Nonparametric tests were used to evaluate relationships between metrics in BCRL participants pre- versus post-MLD (two-sided P < 0.05 required for significance).ResultsB1 dispersion experiments showed nonlinear dependence of Z-values on B1 efficiency in the upper extremities; PTR' showed < 1% mean fractional difference between subject-specific and group-level correction procedures. PTR'APT significantly correlated with T1 (Spearman's rho = 0.57, P < 0.001) and body mass index (Spearman's rho = -0.37, P = 0.029) in controls and with lymphedema stage (Spearman's rho = 0.48, P = 0.017) in BCRL participants. Following MLD therapy, PTR'APT significantly increased in the affected arm of BCRL participants (pre- vs. post-MLD: 0.41 ± 0.05 vs. 0.43 ± 0.03, P = 0.02), consistent with treatment effects from mobilized lymphatic fluid.ConclusionChemical exchange saturation transfer metrics, following appropriate correction procedures, respond to lymphatic mobilization therapies and may have potential for evaluating treatments in participants with secondary lymphedema.

Dataset Information

Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI.

Publications

Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI.

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