A dual 1H/19F birdcage coil for small animals at 7 T MRI.

OBJECTIVE: Given the growing interest in fluorine, it is necessary to develop new multi-tuned RF coils. Therefore, our objective is to design a simple and versatile double-tuned RF coil that can be used as a transmitter and receiver double-tuned coil (1H and 19F) or as transmitter-only double-tuned coil. MATERIALS AND METHODS: A high-pass eight-element birdcage coil was built for 1H and 19F for a 7 T scanner. PIN diodes and cable traps to block unwanted common mode currents in cables were introduced to confer more flexibility to the coil. S-parameters and quality factor were measured in workbench and signal to noise ratio as well as signal intensity profiles in imaging experiments. RESULTS: Bench measurements show S11 values less than - 33 dB, S21 lower than - 13 dB and quality factors ratio of the order of 1.8 that are in agreement with good performances of a RF coil, as well as values of - 39 dB for 19F and - 30 dB for 1H as good detuning values. Signal intensity profiles prove excellent homogeneity at 1H and 19F. DISCUSSION: We present a simple structure of a double-tuned high-pass birdcage coil tuned to 1H and 19F that shows a great uniformity and sensitivity for 19F.

Corrigendum: Impact of a TAK-1 inhibitor as a single or as an add-on therapy to riociguat on the metabolic reprograming and pulmonary hypertension in the SUGEN5416/hypoxia rat model.

[This corrects the article DOI: 10.3389/fphar.2023.1021535.].

Impact of a TAK-1 inhibitor as a single or as an add-on therapy to riociguat on the metabolic reprograming and pulmonary hypertension in the SUGEN5416/hypoxia rat model.

Background: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-ß signaling is believed to be a critical factor in pulmonary vascular remodeling, we hypothesized that blocking TGFß-activated kinase 1 (TAK-1), alone or in combination with a vasodilator therapy (i.e., riociguat) could achieve a greater therapeutic benefit. Methods: PAH was induced in male Wistar rats by a single injection of the VEGF receptor antagonist SU5416 (20 mg/kg) followed by exposure to hypoxia (10%O2) for 21 days. Two weeks after SU5416 administration, vehicle, riociguat (3 mg/kg/day), the TAK-1 inhibitor 5Z-7-oxozeaenol (OXO, 3 mg/kg/day), or both drugs combined were administered for 7 days. Metabolic profiling of right ventricle (RV), lung tissues and PA smooth muscle cells (PASMCs) extracts were performed by magnetic resonance spectroscopy, and the differences between groups analyzed by multivariate statistical methods. Results: In vitro, riociguat induced potent vasodilator effects in isolated pulmonary arteries (PA) with negligible antiproliferative effects and metabolic changes in PASMCs. In contrast, 5Z-7-oxozeaenol effectively inhibited the proliferation of PASMCs characterized by a broad metabolic reprogramming but had no acute vasodilator effects. In vivo, treatment with riociguat partially reduced the increase in pulmonary arterial pressure (PAP), RV hypertrophy (RVH), and pulmonary vascular remodeling, attenuated the dysregulation of inosine, glucose, creatine and phosphocholine (PC) in RV and fully abolished the increase in lung IL-1ß expression. By contrast, 5Z-7-oxozeaenol significantly reduced pulmonary vascular remodeling and attenuated the metabolic shifts of glucose and PC in RV but had no effects on PAP or RVH. Importantly, combined therapy had an additive effect on pulmonary vascular remodeling and induced a significant metabolic effect over taurine, amino acids, glycolysis, and TCA cycle metabolism via glycine-serine-threonine metabolism. However, it did not improve the effects induced by riociguat alone on pulmonary pressure or RV remodeling. None of the treatments attenuated pulmonary endothelial dysfunction and hyperresponsiveness to serotonin in isolated PA. Conclusion: Our results suggest that inhibition of TAK-1 induces antiproliferative effects and its addition to short-term vasodilator therapy enhances the beneficial effects on pulmonary vascular remodeling and RV metabolic reprogramming in experimental PAH.

Fluorine Labeling of Nanoparticles and In Vivo 19F Magnetic Resonance Imaging.

Fluorinated nanoparticles have increasing applications, but they are still challenging to prepare, especially in the case of water-soluble fluorinated nanoparticles. Herein, a fluorine labeling strategy is presented that is based on the conjugation of custom-made small fluorinated building blocks, obtained by simple synthetic transformations, with carboxylated gold nanoparticles through a convenient phase-transfer process. The synthesis of four fluorinated building blocks with different chemical shifts in 19F nuclear magnetic resonance and varied functionalities is reported, along with their conjugation onto nanoparticles. Fluorinated nanoparticles of small core size obtained by this conjugation methodology and by direct synthesis presented high transverse relaxation times (T2) ranging from 518 to 1030 ms, and a large number of equivalent fluorine atoms per nanoparticle (340-1260 fluorine atoms), which made them potential candidates for 19F magnetic resonance related applications. Finally, nontargeted fluorinated nanoparticles were probed by performing in vivo 19F magnetic resonance spectroscopy (19F MRS) in mice. Nanoparticles were detected at both 1 and 2 h after being injected. 19F MRI images were also acquired after either intravenous or subcutaneous injection. Their fate was studied by analyzing the gold content in tissues by ICP-MS. Thus, the present work provides a general fluorination strategy for nanoparticles and shows the potential use of small fluorinated nanoparticles in magnetic-resonance-related applications.

Relevance of control diet choice in metabolic studies: impact in glucose homeostasis and vascular function.

The experimental approach for the study of cardiometabolic disorders requires the use of animal models fed with commercial diets whose composition differs notably, even between diets used for control groups. While chow diets are usually made of agricultural by-products, purified low-fat diets (LF) contain a higher percentage of easy metabolizable carbohydrates, together with a reduced amount of polyunsaturated fatty acids, micronutrients and fiber, all associated with metabolic and vascular dysfunction. We hypothesize that the LF diet, commonly used in control animals, could promote adverse vascular and metabolic outcomes. To address this issue, 5-week-old male C57BL6J mice were fed with a standard (Chow) or a LF diet for 6 weeks. Changes in body weight, adiposity, biochemical parameters, systemic and aortic insulin sensitivity and endothelial function were recorded. LF diet did not modify body weight but significantly impaired systemic glucose tolerance and increased triglycerides and cholesterol levels. Endothelial function and aortic insulin sensitivity were significantly impaired in the LF group, due to a reduction of NO availability. These findings highlight the importance of selecting the proper control diet in metabolic studies. It may also suggest that some cardiometabolic alterations obtained in experimental studies using LF as a control diet may be underestimated.

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile.

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30-65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile.