B1 inhomogeneity correction of RARE MRI at low SNR: Quantitative in vivo 19 F MRI of mouse neuroinflammation with a cryogenically-cooled transceive surface radiofrequency probe.

PURPOSE: Low SNR in fluorine-19 (19 F) MRI benefits from cryogenically-cooled transceive surface RF probes (CRPs), but strong B1 inhomogeneities hinder quantification. Rapid acquisition with refocused echoes (RARE) is an SNR-efficient method for MRI of neuroinflammation with perfluorinated compounds but lacks an analytical signal intensity equation to retrospectively correct B1 inhomogeneity. Here, a workflow was proposed and validated to correct and quantify 19 F-MR signals from the inflamed mouse brain using a 19 F-CRP. METHODS: In vivo 19 F-MR images were acquired in a neuroinflammation mouse model with a quadrature 19 F-CRP using an imaging setup including 3D-printed components to acquire co-localized anatomical and 19 F images. Model-based corrections were validated on a uniform 19 F phantom and in the neuroinflammatory model. Corrected 19 F-MR images were benchmarked against reference images and overlaid on in vivo 1 H-MR images. Computed concentration uncertainty maps using Monte Carlo simulations served as a measure of performance of the B1 corrections. RESULTS: Our study reports on the first quantitative in vivo 19 F-MR images of an inflamed mouse brain using a 19 F-CRP, including in vivo T1 calculations for 19 F-nanoparticles during pathology and B1 corrections for 19 F-signal quantification. Model-based corrections markedly improved 19 F-signal quantification from errors > 50% to < 10% in a uniform phantom (p < 0.001). Concentration uncertainty maps ex vivo and in vivo yielded uncertainties that were generally < 25%. Monte Carlo simulations prescribed SNR ≥ 10.1 to reduce uncertainties < 10%, and SNR ≥ 4.25 to achieve uncertainties < 25%. CONCLUSION: Our model-based correction method facilitated 19 F signal quantification in the inflamed mouse brain when using the SNR-boosting 19 F-CRP technology, paving the way for future low-SNR 19 F-MRI applications in vivo.

Pentafluorosulfanyl (SF5) as a Superior 19F Magnetic Resonance Reporter Group: Signal Detection and Biological Activity of Teriflunomide Derivatives.

Fluorine (19F) magnetic resonance imaging (MRI) is severely limited by a low signal-to noise ratio (SNR), and tapping it for 19F drug detection in vivo still poses a significant challenge. However, it bears the potential for label-free theranostic imaging. Recently, we detected the fluorinated dihydroorotate dehydrogenase (DHODH) inhibitor teriflunomide (TF) noninvasively in an animal model of multiple sclerosis (MS) using 19F MR spectroscopy (MRS). In the present study, we probed distinct modifications to the CF3 group of TF to improve its SNR. This revealed SF5 as a superior alternative to the CF3 group. The value of the SF5 bioisostere as a 19F MRI reporter group within a biological or pharmacological context is by far underexplored. Here, we compared the biological and pharmacological activities of different TF derivatives and their 19F MR properties (chemical shift and relaxation times). The 19F MR SNR efficiency of three MRI methods revealed that SF5-substituted TF has the highest 19F MR SNR efficiency in combination with an ultrashort echo-time (UTE) MRI method. Chemical modifications did not reduce pharmacological or biological activity as shown in the in vitro dihydroorotate dehydrogenase enzyme and T cell proliferation assays. Instead, SF5-substituted TF showed an improved capacity to inhibit T cell proliferation, indicating better anti-inflammatory activity and its suitability as a viable bioisostere in this context. This study proposes SF5 as a novel superior 19F MR reporter group for the MS drug teriflunomide.

Evaluation of a small volume oil-free in vitro production system for bovine embryos.

BACKGROUND: Embryos are usually produced in culture systems with an oil overlay, which conveys protection against the evaporation of water and microbial contamination. The oil can also release toxic substances and absorb essential components, such as hormones, which adversely affect the quality of the oocytes and the development of embryos in vitro. OBJECTIVE: The aim of this study was to validate an oil-free bovine in vitro production (IVP) system. METHOD: Cumulus-oocyte complexes collected from abattoir-derived ovaries were matured, fertilized and cultured employing a standard system. The quantity of medium in both groups (with and without an oil overlay) and throughout all stages of IVP was maintained at a volume of 100 µl. The oil group was covered with paraffin oil. The maturation stage of oocytes was assessed using fluorescence staining after 24 hr and developmental stages of embryos were evaluated on day 8. The expanded day 8 blastocysts were assessed by live-dead staining. RESULTS: Oocytes matured in the absence of an oil overlay had significantly higher maturation rates when compared against matured oocytes in medium with an oil overlay. Steroid concentration is higher in medium after maturation without oil cover. The developmental rate was significantly higher after culture without oil overlay. The total cell number and the live-dead ratio was not significantly different. The osmolality did not differ between both groups during maturation and slightly decreased during culture without oil. CONCLUSION: Based on the current study, bovine oil-free IVP systems can be suggested as an alternative to oil-covered medium.