PURPOSE: A supervised deep learning (DL) approach for frequency and phase correction (FPC) of MRS data recently showed encouraging results, but obtaining transients with labels for supervised learning is challenging. This work investigates the feasibility and efficiency of unsupervised deep learning-based FPC. METHODS: Two novel deep learning-based FPC methods (deep learning-based Cr referencing and deep learning-based spectral registration), which use a priori physics domain knowledge, are presented. The proposed networks were trained, validated, and evaluated using simulated, phantom, and publicly accessible in vivo MEGA-edited MRS data. The performance of our proposed FPC methods was compared with other generally used FPC methods, in terms of precision and time efficiency. A new measure was proposed in this study to evaluate the FPC method performance. The ability of each of our methods to carry out FPC at varying SNR levels was evaluated. A Monte Carlo study was carried out to investigate the performance of our proposed methods. RESULTS: The validation using low-SNR manipulated simulated data demonstrated that the proposed methods could perform FPC comparably with other methods. The evaluation showed that the deep learning-based spectral registration over a limited frequency range method achieved the highest performance in phantom data. The applicability of the proposed method for FPC of GABA-edited in vivo MRS data was demonstrated. Our proposed networks have the potential to reduce computation time significantly. CONCLUSIONS: The proposed physics-informed deep neural networks trained in an unsupervised manner with complex data can offer efficient FPC of large MRS data in a shorter time.

• Klíčová slova
• MR spectroscopy, deep learning, edited MRS, frequency correction, phase correction,
• MeSH
• deep learning * MeSH
• fantomy radiodiagnostické MeSH
• metoda Monte Carlo MeSH
• neuronové sítě (počítačové) MeSH
• počítačové zpracování obrazu metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In this study, we present a method for the detection of n-3 fatty acid (n-3 FA) signals using MRS in adipose tissue in vivo. This method (called oMEGA-PRESS) is based on the selective detection of the CH3 signal of n-3 FA using the MEGA-PRESS (MEshcher-GArwood Point-RESolved Spectroscopy) J-difference editing technique. We optimized the envelope shape and frequency of spectral editing pulses to minimize the spurious co-editing and incomplete subtraction of the CH3 signal of other FAs, which normally obscure the n-3 FA CH3 signal in MR spectra acquired using standard PRESS techniques. The post-processing of the individual data scans with the phase and frequency correction before data subtraction and averaging was implemented to further improve the quality of in vivo spectra. The technique was optimized in vitro on lipid phantoms using various concentrations of n-3 FA and examined in vivo at 3 T on 15 healthy volunteers. The proportion of n-3 FA estimated by the oMEGA-PRESS method in phantoms showed a highly significant linear correlation with the n-3 FA content determined by gas chromatography. The signal attributed to n-3 FA was observed in all subjects. Comparisons with the standard PRESS technique revealed an enhanced identification of the n-3 FA signal using oMEGA-PRESS. The presented method may be useful for the non-invasive quantification of n-3 FA in adipose tissue, and could aid in obtaining a better understanding of various aspects of n-3 FA metabolism.

• Klíčová slova
• J-difference editing, MEGA-PRESS, in vivo MRS, n-3 fatty acids, oMEGA-PRESS,
• MeSH
• chromatografie plynová MeSH
• fantomy radiodiagnostické MeSH
• index tělesné hmotnosti MeSH
• kyseliny mastné omega-3 analýza   MeSH
• lidé MeSH
• lněný olej chemie   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• oleje rostlin chemie   MeSH
• podkožní tuk chemie   MeSH
• slunečnicový olej MeSH
• tuková tkáň chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyseliny mastné omega-3 MeSH
• lněný olej MeSH
• oleje rostlin MeSH
• slunečnicový olej MeSH

BACKGROUND & AIMS: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. METHODS: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. RESULTS: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. CONCLUSIONS: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. LAY SUMMARY: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer.

• Klíčová slova
• 14q32, BLCAP, CHKA, DLK1-DIO3 locus, Hepatoblastoma (HB), Molecular risk stratification, Prognostic biomarker, RNA editing,
• MeSH
• beta-katenin genetika   MeSH
• cholinkinasa * antagonisté a inhibitory   metabolismus   MeSH
• epigeneze genetická MeSH
• hepatoblastom * genetika   metabolismus   mortalita   patologie   MeSH
• hodnocení rizik metody   MeSH
• kojenec MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• metylace DNA MeSH
• nádorové biomarkery analýza   MeSH
• nádorové proteiny genetika   MeSH
• nádory jater * genetika   metabolismus   mortalita   patologie   MeSH
• objevování léků metody   MeSH
• prognóza MeSH
• proteiny vázající vápník genetika   MeSH
• rychlé screeningové testy MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• beta-katenin MeSH
• BLCAP protein, human MeSH Prohlížeč
• CHKA protein, human MeSH Prohlížeč
• cholinkinasa * MeSH
• CTNNB1 protein, human MeSH Prohlížeč
• DLK1 protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• nádorové biomarkery MeSH
• nádorové proteiny MeSH
• proteiny vázající vápník MeSH

AIMS: The aim of our study was to assess the yield of routine brain magnetic resonance imaging (MRI) performed at our hospital as part of the diagnostic procedures focused on autism. METHODS: Our retrospective study involved children who had attended a diagnostic examination focused on autism and underwent brain MRIs between 1998-2015. The International Classification of Diseases, 10th edition was used to make clinical diagnoses. In 489 children (404 boys, 85 girls; mean age 8.0±4.2 years), a diagnosis of a pervasive developmental disorder was confirmed. Forty-five children, where the autism diagnosis was ruled out (but other psychiatric diagnoses found), served as a control group (36 boys, 9 girls; mean age 7.0±2.4 years). We can assume that in such a control group, brain abnormalities might occur at a higher frequency than in truly healthy children which would have the effect of reducing the difference between the groups. RESULTS: MRI pathologies were more common in the autistic (45.4 %) compared to the control group (31.8%) but the difference was significant only at the trend level (P=0.085). Hypoplasia of the corpus callosum (CC) was significantly more common in the autistic vs. the control group (13.7 vs. 0%; P=0.009). In contrast, nonmyelinated areas of white matter were significantly more common in controls (31.8 vs.17.3%; P=0.018). Differences in other parameters were not significant. CONCLUSION: The occurrence of CC hypoplasia on routine MRI scans could represent a "red flag" for suspicion of autism.

• Klíčová slova
• MRI, autism spectrum disorders, brain, corpus callosum,
• MeSH
• autistická porucha diagnostické zobrazování   MeSH
• dítě MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladiství MeSH
• mozek diagnostické zobrazování   patofyziologie   MeSH
• poruchy autistického spektra diagnóza   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To update the 2011 ESTRO-EFOMP core curriculum (CC) for education and training of medical physics experts (MPE)s working in radiotherapy (RT), in line with recent EU guidelines, and to provide a framework for European countries to develop their own curriculum. MATERIAL AND METHODS: Since September 2019, 27 European MPEs representing ESTRO, EFOMP and National Societies, with expertise covering all subfields of RT physics, have revised the CC for recent advances in RT. The ESTRO and EFOMP Education Councils, all European National Societies and international stakeholders have been involved in the revision process. RESULTS: A 4-year training period has been proposed, with a total of 240 ECTS (European Credit Transfer and Accumulation System). Training entrance levels have been defined ensuring the necessary physics and mathematics background. The concept of competency-based education has been reinforced by introducing the CanMEDS role framework. The updated CC includes (ablative) stereotactic-, MR-guided- and adaptive RT, particle therapy, advanced automation, complex quantitative data analysis (big data/artificial intelligence), use of biological images, and personalized treatments. Due to the continuously increasing RT complexity, more emphasis has been given to quality management. Clear requirements for a research project ensure a proper preparation of MPE residents for their central role in science and innovation in RT. CONCLUSION: This updated, 3rd edition of the CC provides an MPE training framework for safe and effective practice of modern RT, while acknowledging the significant efforts needed in some countries to reach this level. The CC can contribute to further harmonization of MPE training in Europe.

• Klíčová slova
• Core curriculum (CC), ESTRO-EFOMP, Education and training, Medical Physics Expert (MPE), Radiotherapy physics,
• MeSH
• biofyzika záření výchova   MeSH
• kurikulum MeSH
• lidé MeSH
• radiační onkologie * výchova   MeSH
• umělá inteligence * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH