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Advanced science (2021). doi:10.1002/advs.202100370, Published by Wiley-VCH, Weinheim

The first aim of this study was to determine how complete or perivascular loss of aquaporin-4 (AQP4) water channels affects membrane permeability for water in the mouse brain grey matter in the steady state. Time-dependent diffusion magnetic resonance imaging was performed on global Aqp4 knock out (KO) and α-syntrophin (α-syn) KO mice, in the latter perivascular AQP4 are mislocalized, but still functioning. Control animals were corresponding wild type (WT) mice. By combining in vivo diffusion measurements with the effective medium theory and previously measured extra-cellular volume fractions, the effects of membrane permeability and extracellular volume fraction were uncoupled for Aqp4 and α-syn KO. The second aim was to assess the effect of α-syn KO on cortical intermediary metabolism combining in vivo [1-13C]glucose and [1,2-13C]acetate injection with ex vivo 13C MR spectroscopy. Aqp4 KO increased the effective diffusion coefficient at long diffusion times by 5%, and a 14% decrease in membrane water permeability was estimated for Aqp4 KO compared with WT mice. α-syn KO did not affect the measured diffusion parameters. In the metabolic analyses, significantly lower amounts of [4-13C]glutamate and [4-13C]glutamine, and percent enrichment in [4-13C]glutamate were detected in the α-syn KO mice. [1,2-13C]acetate metabolism was unaffected in α-syn KO, but the contribution of astrocyte derived metabolites to GABA synthesis was significantly increased. Taken together, α-syn KO mice appeared to have decreased neuronal glucose metabolism, partly compensated for by utilization of astrocyte derived metabolites. This is the authors' accepted and refereed manuscript to the article. Locked until 30 December 2017 due to copyright restrictions. The final publication is available at link.springer.com via https://link.springer.com/article/10.1007%2Fs11064-016-2139-y

There are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI) of physiological parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK) cells. Contrast enhanced conventional T1-weighted MRI at 761 and 1762 days posttreatment failed to detect differences in tumour size between the treatment groups, whereas, follow-up scans at 3 months demonstrated diminished signal intensity and tumour volume in the surviving NK+mAb9.2.27 treated animals. Notably, interstitial volume fraction (ve), was significantly increased in the NK+mAb9.2.27 combination therapy group compared mAb9.2.27 and NK cell monotherapy groups (p = 0.002 and p = 0.017 respectively) in cohort 1 animals treated with 1 million NK cells. ve was reproducibly increased in the combination NK+mAb9.2.27 compared to NK cell monotherapy in cohort 2 treated with increased dose of 2 million NK cells (p,0.0001), indicating greater cell death induced by NK+mAb9.2.27 treatment. The interstitial volume fraction in the NK monotherapy group was significantly reduced compared to mAb9.2.27 monotherapy (p,0.0001) and untreated controls (p = 0.014) in the cohort 2 animals. NK cells in monotherapy were unable to kill the U87MG cells that highly expressed class I human leucocyte antigens, and diminished stress ligands for activating receptors. A significant association between apparent diffusion coefficient (ADC) of water and ve in combination NK+ mAb9.2.27 and NK monotherapy treated tumours was evident, where increased ADC corresponded to reduced ve in both cases. Collectively, these data support histological measures at end-stage demonstrating diminished tumour cell proliferation and pronounced apoptosis in the NK+mAb9.2.27 treated tumours compared to the other groups. In conclusion, ve was the most reliable radiological parameter for detecting response to intralesional NK cellular therapy. (c) 2014 Rygh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Introduction The MRI contrast media manganese-dipyridoxyl-diphosphate (MnDPDP) has been shown to be a marker of viability in patients with myocardial infarction, as manganese-ions follow the calcium-pathways and accumulate in viable myocardial cells. However, the contrastto-noise ratio is presently too low for clinical use. In a previous study in rats given manganese-cloride (MnCl2), dobutamine increased the myocardial uptake of Mn significantly.

Objectives We have explored the usefulness of an on-table, cross-sectional radiological imaging (DynaCT) in endovascular aortic repair (EVAR). DynaCT images were compared to images from a regular multidetector (16 slice) CT. In the comparison, we tested the accordance of firstly 5 relevant clinical measurements and secondly the visibility of 9 anatomical areas in the two different types of images. This imaging was carried out in addition to the usual angiographic imaging. Design, material and method 20 patients with infrarenal abdominal aortic aneurysm (AAA) were prospectively enrolled in the study. We compared Images from DynaCT with two different doses of contrast medium to MDCT-images in two different ways. Firstly relevant arterial diameters and lengths and secondly, 9 anatomical areas were evaluated regarding visibility which was scored on a 4-point scale. Results There were no significant differences in the measured arterial diameters and lengths. MDCT had a significantly higher visibility score than both DynaCT investigations. However, with the highest contrast medium dose we found acceptable diagnostic quality in 78–94% of the cases for 8 of the 9 investigated anatomical areas. Conclusion Our findings indicate that on-table DynaCT are of sufficient quality to give relevant information of arterial measurements, needed in endovascular repair of infrarenal aortic aneurysms.