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Background and Purpose: The heart is important in radiotherapy either as target or organ at risk. Quantitative T1 and T2 cardiac magnetic resonance imaging (qMRI) may aid in target definition for cardiac radioablation, and imaging biomarker for cardiotoxicity assessment. Hybrid MR-linac devices could facilitate daily cardiac qMRI of the heart in radiotherapy. The aim of this work was therefore to enable cardiac-synchronized T1 and T2 mapping on a 1.5 T MR-linac and test the reproducibility of these sequences on phantoms and in vivo between the MR-linac and a diagnostic 1.5 T MRI scanner. Materials and methods: Cardiac-synchronized MRI was performed on the MR-linac using a wireless peripheral pulse-oximeter unit. Diagnostically used T1 and T2 mapping sequences were acquired twice on the MR-linac and on a 1.5 T MR-simulator for a gel phantom and 5 healthy volunteers in breath-hold. Phantom T1 and T2 values were compared to gold-standard measurements and percentage errors (PE) were computed, where negative/positive PE indicate underestimations/overestimations. Manually selected regions-of-interest were used for in vivo intra/inter scanner evaluation. Results: Cardiac-synchronized T1 and T2 qMRI was enabled after successful hardware installation on the MR-linac. From the phantom experiments, the measured T1/T2 relaxation times had a maximum percentage error (PE) of −4.4%/−8.8% on the MR-simulator and a maximum PE of −3.2%/+8.6% on the MR-linac. Mean T1/T2 of the myocardium were 1012±34/51±2 ms on the MR-simulator and 1034±42/51±1 ms on the MR-linac. Conclusions: Accurate cardiac-synchronized T1 and T2 mapping is feasible on a 1.5 T MR-linac and might enable novel plan adaptation workflows and cardiotoxicity assessments.

Pregnancy complications such as preeclampsia cause increased fetal oxidative stress and fetal growth restriction, and associate with a higher incidence of adult metabolic syndrome. However, the pathophysiological contribution of oxidative stress per se is experimentally difficult to discern and has not been investigated. This study determined, if increased intrauterine oxidative stress (IUOx) affects adiposity, glucose and cholesterol metabolism in adult Ldlr−/−xSod2+/+ offspring from crossing male Ldlr−/−xSod2+/+ mice with Ldlr−/−xSod2 +/- dams (IUOx) or Ldlr−/−xSod2 +/- males with Ldlr−/−xSod2+/+ dams (control). At 12 weeks of age mice received Western diet for an additional 12 weeks. Adult male IUOx offspring displayed lower body weight and reduced adiposity associated with improved glucose tolerance compared to controls. Reduced weight gain in IUOx was conceivably due to increased energy dissipation in white adipose tissue conveyed by higher expression of Ucp1 and an accompanying decrease in DNA methylation in the Ucp1 enhancer region. Female offspring did not show comparable phenotypes. These results demonstrate that fetal oxidative stress protects against the obesogenic effects of Western diet in adulthood by programming energy dissipation in white adipose tissue at the level of Ucp1. Keywords: Fetal oxidative stress, Mitohormesis, Metabolic programming, Adiposity, Epigenetics, Methylation

Background and purpose: Diffusion weighted (DW) MRI may facilitate target volume delineation for head-and-neck (HN) radiation treatment planning. In this study we assessed the use of a dedicated, geometrically accurate, DW-MRI sequence for target volume delineation. The delineations were compared with semi-automatic segmentations on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images and evaluated for interobserver variation. Methods and materials: Fifteen HN cancer patients underwent both DW-MRI and FDG-PET for RT treatment planning. Target delineation on DW-MRI was performed by three observers, while for PET a semi-automatic segmentation was performed using a Gaussian mixture model. For interobserver variation and intermodality variation, volumes, overlap metrics and Hausdorff distances were calculated from the delineations. Results: The median volumes delineated by the three observers on DW-MRI were 10.8, 10.5 and 9.0 cm3 respectively, and was larger than the median PET volume (8.0 cm3). The median conformity index of DW-MRI for interobserver variation was 0.73 (range 0.38–0.80). Compared to PET, the delineations on DW-MRI by the three observers showed a median dice similarity coefficient of 0.71, 0.69 and 0.72 respectively. The mean Hausdorff distance was small with median (range) distances between PET and DW-MRI of 2.3 (1.5–6.8), 2.5 (1.6–6.9) and 2.0 (1.35–7.6) mm respectively. Over all patients, the median 95th percentile distances were 6.0 (3.0–13.4), 6.6 (4.0–24.0) and 5.3 (3.4–26.0) mm. Conclusion: Using a dedicated DW-MRI sequence, target volumes could be defined with good interobserver agreement and a good overlap with PET. Target volume delineation using DW-MRI is promising in head-and-neck radiotherapy, combined with other modalities, it can lead to more precise target volume delineation. Keywords: Radiotherapy, Head and neck, Target volume delineation, Diffusion MRI, PET

Hodgkin lymphoma (HL) is derived from preapoptotic germinal center B cells, although a general loss of B cell phenotype is noted. Using quantitative reverse transcription-polymerase chain reaction and miRNA microarray, we determined the microRNA (miRNA) profile of HL and compared this with the profile of a panel of B-cell non-Hodgkin lymphomas. The two methods showed a strong correlation for the detection of miRNA expression levels. The HL-specific miRNA included miR-17-92 cluster members, miR-16, miR-21, miR-24, and miR-155. Using a large panel of cell lines, we found differential expression between HL and other B-cell lymphoma-derived cell lines for 27 miRNA. A significant down-regulation in HL compared to non-Hodgkin lymphoma was observed only for miR-150. Next, we performed target gene validation of predicted target genes for miR-155, which is highly expressed in HL and is differentially expressed between HL and Burkitt lymphoma. Using luciferase reporter assays, we validated 11 predicted miR-155 target genes in three different HL cell lines. We demonstrated that AGTR1, FGF7, ZNF537, ZIC3, and IKBKE are true miR-155 target genes in HL.