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Background: To overcome flow and electrocardiogram-trigger artifacts in cardiovascular magnetic resonance (CMR), we have implemented a cardiac and respiratory self-gated cine ultra-short echo time (UTE) sequence. We have assessed its performance in healthy mice by comparing the results with those obtained with a self-gated cine fast low angle shot (FLASH) sequence and with echocardiography. Methods: 2D self-gated cine UTE (TE/TR = 314 μs/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 5 min 5 sec) and self-gated cine FLASH (TE/TR = 3 ms/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 4 min 49 sec) images were acquired at 9.4 T. Volume of the left and right ventricular (LV, RV) myocardium as well as the end-diastolic and - systolic volume was segmented manually in MR images and myocardial mass, stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were determined. Statistical differences were analyzed by using Student t test and Bland-Altman analyses. Results: Self-gated cine UTE provided high quality images with high contrast-to-noise ratio (CNR) also for the RV myocardium (CNRblood-myocardium = 25.5 ± 7.8). Compared to cine FLASH, susceptibility, motion, and flow artifacts were considerably reduced due to the short TE of 314 μs. The aortic valve was clearly discernible over the entire cardiac cycle. Myocardial mass, SV, EF and CO determined by self-gated UTE were identical to the values measured with selfgated FLASH and showed good agreement to the results obtained by echocardiography. Conclusions: Self-gated UTE allows for robust measurement of cardiac parameters of diagnostic interest. Image quality is superior to self-gated FLASH, rendering the method a powerful alternative for the assessment of cardiac function at high magnetic fields. [ABSTRACT FROM AUTHOR]

Background: Detection of inflamed atherosclerotic plaques is of crucial importance. The carotid artery cuff-model in ApoE−/− mice results in shear-stress induced atherosclerosis with inflamed plaques upstream (US) and ‘stable’ plaques downstream (DS) of the cuff. We evaluated the potential of F-18-FDG PET/CT to differentiate these plaque phenotypes. Methods: A predefined cuff was implanted round the left (n = 23) or right (n = 12) common carotid artery (CCA) of 35 ApoE−/− mice on a cholesterol-rich diet. Small animal F-18-FDG PET/CT was performed after 4, 6 and 8 weeks. F-18-FDG uptake was quantified US and DS of the cuff and on the contralateral CCA. Subsequently, regional F-18-FDG uptake was normalized by the contralateral CCA uptake to obtain plaque-to-background (P/B)-ratios. Thereafter, CCA were explanted and investigated by immunohistology. Results: P/B-ratio in the US-plaques increased from 1.22 ± 0.23 at 4 weeks over 1.23 ± 0.32 at 6 weeks to 1.37 ± 0.56 (p = ns) at 8 weeks after cuff implantation (left and right side of cuff implantation considered together). Uptake in the DS-plaques remained stable (1.14 ± 0.23, 1.10 ± 0.26 and 1.11 ± 0.25; p = ns). Uptake in the US-plaques was significantly higher than in the DS-plaques (all p < 0.05). P/B-ratios correlated with plaque size, degree of stenosis and macrophage density in the plaques. Moreover, there was a correlation between plaque size and macrophage density in the plaque. Conclusions: F-18-FDG-PET/CT distinguishes atherosclerotic plaques with an inflamed from those with a ‘stable’ phenotype in a mouse model of shear-stress induced atherosclerosis in vivo. [ABSTRACT FROM AUTHOR]

Despite treatments combining surgery, radiation-, and chemotherapy, patients affected by glioblastoma (GBM) have a limited prognosis. Addition of temozolomide (TMZ) to radiation therapy is the standard therapy in clinical application, but effectiveness of TMZ is limited by the tumor's overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). The goal of this study was to use the highly specific and efficient RNA interference (RNAi) pathway to modulate MGMT expression to increase TMZ efficiency in chemotherapy resistant GBM. Using lentiviral-based anti-MGMT small hairpin RNA (shRNA) technology we observed a specific inhibition of the MGMT expression in GBM cell lines as well as in subcutaneous tumors. Tumor growth inhibition was observed following TMZ treatment of xenografts with low MGMT expression in contrast to xenografts with high MGMT expression. Bioluminescence imaging (BLI) measurements indicated that luciferase and shRNA-expressing lentiviruses were able to efficiently transduce the GBM xenografts in vivo. Treatment combining injection of a lentivirus expressing an anti-MGMT shRNA and TMZ induced a reduction of the size of the tumors, in contrast with treatment combining the lentivirus expressing the control shRNA and TMZ. Our data suggest that anti-MGMT shRNA therapy could be used in combination with TMZ chemotherapy in order to improve the treatment of resistant GBM. [ABSTRACT FROM AUTHOR]