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Neuroinflammation can be monitored using fluorine-19 (19F)-containing nanoparticles and 19F MRI. Previously we studied neuroinflammation in experimental autoimmune encephalomyelitis (EAE) using room temperature (RT) 19F radiofrequency (RF) coils and low spatial resolution 19F MRI to overcome constraints in signal-to-noise ratio (SNR). This yielded an approximate localization of inflammatory lesions. Here we used a new 19F transceive cryogenic quadrature RF probe (19 F-CRP) that provides the SNR necessary to acquire superior spatially-resolved 19F MRI. First we characterized the signal-transmission profile of the 19 F-CRP. The 19 F-CRP was then benchmarked against a RT 19F/1H RF coil. For SNR comparison we used reference compounds including 19F-nanoparticles and ex vivo brains from EAE mice administered with 19F-nanoparticles. The transmit/receive profile of the 19 F-CRP diminished with increasing distance from the surface. This was counterbalanced by a substantial SNR gain compared to the RT coil. Intraparenchymal inflammation in the ex vivo EAE brains was more sharply defined when using 150 μm isotropic resolution with the 19 F-CRP, and reflected the known distribution of EAE histopathology. At this spatial resolution, most 19F signals were undetectable using the RT coil. The 19 F-CRP is a valuable tool that will allow us to study neuroinflammation with greater detail in future in vivo studies.

Background: The use of rigid multi-exponential models (with a priori predefined numbers of components) is common practice for diffusion-weighted MRI (DWI) analysis of the kidney. This approach may not accurately reflect renal microstructure, as the data are forced to conform to the a priori assumptions of simplified models. This work examines the feasibility of less constrained, data-driven non-negative least squares (NNLS) continuum modelling for DWI of the kidney tubule system in simulations that include emulations of pathophysiological conditions.Methods: Non-linear least squares (LS) fitting was used as reference for the simulations. For performance assessment, a threshold of 5% or 10% for the mean absolute percentage error (MAPE) of NNLS and LS results was used. As ground truth, a tri-exponential model using defined volume fractions and diffusion coefficients for each renal compartment (tubule system: D tubules , f tubules ; renal tissue: D tissue , f tissue ; renal blood: D blood , f blood ;) was applied. The impact of: (I) signal-to-noise ratio (SNR) =40-1,000, (II) number of b-values (n=10-50), (III) diffusion weighting (b-range small =0-800 up to b-range large =0-2,180 s/mm 2 ), and (IV) fixation of the diffusion coefficients D tissue and D blood was examined. NNLS was evaluated for baseline and pathophysiological conditions, namely increased tubular volume fraction (ITV) and renal fibrosis (10%: grade I, mild) and 30% (grade II, moderate).Results: NNLS showed the same high degree of reliability as the non-linear LS. MAPE of the tubular volume fraction (f tubules ) decreased with increasing SNR. Increasing the number of b-values was beneficial for f tubules precision. Using the b-range large led to a decrease in MAPE ftubules compared to b-range small . The use of a medium b-value range of b=0-1,380 s/mm 2 improved f tubules precision, and further b max increases beyond this range yielded diminishing improvements. Fixing D blood and D tissue significantly reduced MAPE ftubules and provided near perfect distinction between baseline and ITV conditions. Without constraining the number of renal compartments in advance, NNLS was able to detect the (fourth) fibrotic compartment, to differentiate it from the other three diffusion components, and to distinguish between 10% vs. 30% fibrosis.Conclusions: This work demonstrates the feasibility of NNLS modelling for DWI of the kidney tubule

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Purpose The use of surface radiofrequency (RF) coils is common practice to boost sensitivity in (pre)clinical MRI. The number of transceive surface RF coils is rapidly growing due to the surge in cryogenically cooled RF technology and ultrahigh‐field MRI. Consequently, there is an increasing need for effective correction of the excitation field ( B1+) inhomogeneity inherent in these coils. Retrospective B1 correction permits quantitative MRI, but this usually requires a pulse sequence‐specific analytical signal intensity (SI) equation. Such an equation is not available for fast spin‐echo (Rapid Acquisition with Relaxation Enhancement, RARE) MRI. Here we present, test, and validate retrospective B1 correction methods for RARE. Methods We implemented the commonly used sensitivity correction and developed an empirical model‐based method and a hybrid combination of both. Tests and validations were performed with a cryogenically cooled RF probe and a single‐loop RF coil. Accuracy of SI quantification and T1 contrast were evaluated after correction. Results The three described correction methods achieved dramatic improvements in B1 homogeneity and significantly improved SI quantification and T1 contrast, with mean SI errors reduced from >40% to >10% following correction in all cases. Upon correction, images of phantoms and mouse heads demonstrated homogeneity comparable to that of images acquired with a volume resonator. This was quantified by SI profile, SI ratio (error < 10%), and percentage of integral uniformity (PIU > 80% in vivo and ex vivo compared to PIU > 87% with the reference RF coil). Conclusion This work demonstrates the efficacy of three B1 correction methods tailored for transceive surface RF probes and RARE MRI. The corrected images are suitable for quantification and show comparable results between the three methods, opening the way for T1 measurements and X‐nuclei quantification using surface transceiver RF coils. This approach is applicable to other MR techniques for which no analytical SI exists.

Fluorine ( 19 F) magnetic resonance imaging (MRI) is severely limited by a low signal-to noise ratio (SNR), and tapping it for 19 F 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 19 F MR spectroscopy (MRS). In the present study, we probed distinct modifications to the CF 3 group of TF to improve its SNR. This revealed SF 5 as a superior alternative to the CF 3 group. The value of the SF 5 bioisostere as a 19 F 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 19 F MR properties (chemical shift and relaxation times). The 19 F MR SNR efficiency of three MRI methods revealed that SF 5 -substituted TF has the highest 19 F 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, SF 5 -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 SF 5 as a novel superior 19 F MR reporter group for the MS drug teriflunomide.

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Objective Fluorine MR would benefit greatly from enhancements in signal-to-noise ratio (SNR). This study examines the sensitivity gain of 19 F MR that can be practically achieved when moving from 9.4 to 21.1 T. Materials and methods We studied perfluoro-15-crown-5-ether (PFCE) at both field strengths (B 0 ), as a pure compound, in the form of nanoparticles (NP) as employed to study inflammation in vivo, as well as in inflamed tissue. Brains, lymph nodes (LNs) and spleens were obtained from mice with experimental autoimmune encephalomyelitis (EAE) that had been administered PFCE NPs. All samples were measured at both B 0 with 2D-RARE and 2D-FLASH using 19 F volume radiofrequency resonators together. T 1 and T 2 of PFCE were measured at both B 0 strengths. Results Compared to 9.4 T, an SNR gain of > 3 was observed for pure PFCE and > 2 for PFCE NPs at 21.1 T using 2D-FLASH. A dependency of 19 F T 1 and T 2 relaxation on B 0 was demonstrated. High spatially resolved 19 F MRI of EAE brains and LNs at 21.1 T revealed signals not seen at 9.4 T. Discussion Enhanced SNR and T 1 shortening indicate the potential benefit of in vivo 19 F MR at higher B 0 to study inflammatory processes with greater detail. Electronic supplementary material The online version of this article (10.1007/s10334-018-0710-z) contains supplementary material, which is available to authorized users.