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3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1518-1528.

are current employees of Geneplus-Beijing. C. Wang and Z. Yu are current employees of Geneplus-Shenzhen. L. Yang holds leadership positions of Geneplus-Beijing. The other authors declare no conflicts of interest. Translational Relevance Neoadjuvant chemoradiotherapy (nCRT) was the standard of care for patients with locally advanced rectal cancer (LARC), however the uniform regimen may not be applicable for all patients with different tumor loads and heterogeneous biological behaviors. In this study, the preoperative ctDNA status was significantly consistent with the postoperative pathological results, showing that ctDNA can accurately reflect the real-time tumor burden. Additionally, ctDNA showed a predictive ability for distant metastasis as early as prior to treatment. Besides, tumors with POLD1 mutation had significantly better response to nCRT than those without POLD1 mutation. These findings imply that ctDNA and tumor mutational information may potentially be powerful tools to guide the individualized multidisciplinary therapy for patients with LARC by assisting the selection of initial treatment strategies and regimens, or guiding the adjustment of treatment methods.

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Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute proteins and peptides as well as microenvironmental properties. However, the complexity of the CEST MRI effect, which varies with the labile proton content, exchange rate and experimental conditions, underscores the need for development of quantitative CEST (qCEST) analysis. Towards this goal, it has been shown that the omega plot is capable of quantifying paramagnetic CEST (PARACEST) MRI. However, the use of omega plot is somewhat limited for diamagnetic CEST (DIACEST) MRI because it is more susceptible to direct RF saturation (spillover) effects owing to their relatively small chemical shift. Recently, it has been found that for dilute DIACEST agents that undergo slow to intermediate chemical exchange, the RF spillover effect varies little with the labile proton ratio and exchange rate. Therefore, we postulated that the omega plot analysis can be improved if RF spillover effect could be estimated and taken into account. Specifically, simulation showed that both labile proton ratio and exchange rate derived using the spillover effect-corrected omega plot are in good agreement with simulated values. In addition, the modified omega plot was confirmed experimentally, and we showed that the derived labile proton ratio increases linearly with creatine concentration (P< 0.01), with little difference in their exchange rate (P=0.32). In summary, our study extended the conventional omega plot for quantitative analysis of DIACEST MRI.

Our previous studies demonstrate that CXCL6/CXCR6 chemokine axis induces prostate cancer progression by the AKT/mTOR signaling pathway; however, its role and mechanisms underlying invasiveness and metastasis of breast cancer are yet to be elucidated. In this investigation, CXCR6 protein expression was examined using high-density tissue microarrays and immunohistochemistry. Expression of CXCR6 shows a higher epithelial staining in breast cancer nest site and metastatic lymph node than the normal breast tissue, suggesting that CXCR6 may be involved in breast cancer (BC) development. In vitro and in vivo experiments indicate that overexpression of CXCR6 in BC cells has a marked effect on increasing cell migration, invasion and metastasis. In contrast, reduction of CXCR6 expression by shRNAs in these cells greatly reduce its invasion and metastasis ability. Mechanistic analyses show that CXCL16/CXCR6 chemokine axis is capable of modulating activation of RhoA through activating ERK1/2 signaling pathway, which then inhibits the activity of cofilin, thereby enhancing the stability of F-actin, responsible for invasiveness and metastasis of BC.Taken together, our data shows for the first time that the CXCR6 / ERK1/2/ RhoA / cofilin /F-actin pathway plays a central role in the development of BC. Targeting the signaling pathway may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for BC.

pH-sensitive chemical exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, CEST effect depends on not only exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used X-Ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent chemical exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T1 and T2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20 mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH above 7. Moreover, we determined base-catalyzed chemical exchange for 2-hydrooxypropanamido (ksw=1.2*10pH−4.1) and amide (ksw=1.2*10pH−4.6) protons that are statistically different from each other (P<0.01, ANCOVA), understanding of which should help guide in vivo translation of iopamidol pH imaging.

BackgroundThe methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with treatment response in glioblastoma(GBM). Using pre-operative MRI techniques to predict MGMT promoter methylation status remains inconclusive. In this study, we investigated the value of features from structural and advanced imagings in predicting the methylation of MGMT promoter in primary glioblastoma patients.MethodsNinety-two pathologically confirmed primary glioblastoma patients underwent preoperative structural MR imagings and the efficacy of structural image features were qualitatively analyzed using Fisher’s exact test. In addition, 77 of the 92 patients underwent additional advanced MRI scans including diffusion-weighted (DWI) and 3-diminsional pseudo-continuous arterial spin labeling (3D pCASL) imaging. Apparent diffusion coefficient (ADC) and relative cerebral blood flow (rCBF) values within the manually drawn region-of-interest (ROI) were calculated and compared using independent sample t test for their efficacies in predicting MGMT promoter methylation. Receiver operating characteristic curve (ROC) analysis was used to investigate the predicting efficacy with the area under the curve (AUC) and cross validations. Multiple-variable logistic regression model was employed to evaluate the predicting performance of multiple variables.ResultsMGMT promoter methylation was associated with tumor location and necrosis (P <  0.05). Significantly increased ADC value (P <  0.001) and decreased rCBF (P <  0.001) were associated with MGMT promoter methylation in primary glioblastoma. The ADC achieved the better predicting efficacy than rCBF (ADC: AUC, 0.860; sensitivity, 81.1%; specificity, 82.5%; vs rCBF: AUC, 0.835; sensitivity, 75.0%; specificity, 78.4%; P = 0.032). The combination of tumor location, necrosis, ADC and rCBF resulted in the highest AUC of 0.914.ConclusionADC and rCBF are promising imaging biomarkers in clinical routine to predict the MGMT promoter methylation in primary glioblastoma patients.