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The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
Safety of subjects during radiofrequency exposure in ultra-high-field magnetic resonance imaging
(2020)
Magnetic resonance imaging (MRI) is one of the most important medical imaging techniques. Since the introduction of MRI in the mid-1980s, there has been a continuous trend toward higher static magnetic fields to obtain i.a. a higher signal-to-noise ratio. The step toward ultra-high-field (UHF) MRI at 7 Tesla and higher, however, creates several challenges regarding the homogeneity of the spin excitation RF transmit field and the RF exposure of the subject. In UHF MRI systems, the wavelength of the RF field is in the range of the diameter of the human body, which can result in inhomogeneous spin excitation and local SAR hotspots. To optimize the homogeneity in a region of interest, UHF MRI systems use parallel transmit systems with multiple transmit antennas and time-dependent modulation of the RF signal in the individual transmit channels. Furthermore, SAR increases with increasing field strength, while the SAR limits remain unchanged. Two different approaches to generate the RF transmit field in UHF systems using antenna arrays close and remote to the body are investigated in this letter. Achievable imaging performance is evaluated compared to typical clinical RF transmit systems at lower field strength. The evaluation has been performed under consideration of RF exposure based on local SAR and tissue temperature. Furthermore, results for thermal dose as an alternative RF exposure metric are presented.