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Purpose: To firstly improve the attainable image SNR of 19F and 1H C3F8 lung imaging at 1.5 tesla using an 8‐element transmit/receive (Tx/Rx) flexible vest array combined with a 6‐element Rx‐only array, and to secondly evaluate microelectromechanical systems for switching the array elements between the 2 resonant frequencies. Methods: The Tx efficiency and homogeneity of the 8‐element array were measured and simulated for 1H imaging in a cylindrical phantom and then evaluated for in vivo 19F/1H imaging. The added improvement provided by the 6‐element Rx‐only array was quantified through simulation and measurement and compared to the ultimate SNR. It was verified through the measurement of isolation that microelectromechanical systems switches provided broadband isolation of Tx/Rx circuitry such that the 19F tuned Tx/Rx array could be effectively used for both 19F and 1H nuclei. Results: For 1H imaging, the measured Tx efficiency/homogeneity (mean ± percent SD; 6.79μT/kW±26%) was comparable to that simulated (7.57μT/kW±20%). The 6 additional Rx‐only loops increased the mean Rx sensitivity when compared to the 8‐element array by a factor of 1.41× and 1.45× in simulation and measurement, respectively. In regions central to the thorax, the simulated SNR of the 14‐element array achieves ≥70% of the ultimate SNR when including noise from the matching circuits and preamplifiers. A measured microelectromechanical systems switching speed of 12 µs and added minimum 22 dB of isolation between Tx and Rx were sufficient for Tx/Rx switching in this application. Conclusion: The described single‐tuned array driven at 19F and 1H, utilizing microelectromechanical systems technology, provides excellent results for 19F and 1H dual‐nuclear lung ventilation imaging. [ABSTRACT FROM AUTHOR]

Purpose: A bottleneck in developing cell therapies for cancer is assaying cell biodistribution, persistence, and survival in vivo. Ex vivo cell labeling using perfluorocarbon (PFC) nanoemulsions, paired with 19F MRI detection, is a non‐invasive approach for cell product detection in vivo. Lymphocytes are small and weakly phagocytic limiting PFC labeling levels and MRI sensitivity. To boost labeling, we designed PFC nanoemulsion imaging probes displaying a cell‐penetrating peptide, namely the transactivating transcription sequence (TAT) of the human immunodeficiency virus. We report optimized synthesis schemes for preparing TAT co‐surfactant to complement the common surfactants used in PFC nanoemulsion preparations. Methods: We performed ex vivo labeling of primary human chimeric antigen receptor (CAR) T cells with nanoemulsion. Intracellular labeling was validated using electron microscopy and confocal imaging. To detect signal enhancement in vivo, labeled CAR T cells were intra‐tumorally injected into mice bearing flank glioma tumors. Results: By incorporating TAT into the nanoemulsion, a labeling efficiency of ~1012 fluorine atoms per CAR T cell was achieved that is a >8‐fold increase compared to nanoemulsion without TAT while retaining high cell viability (~84%). Flow cytometry phenotypic assays show that CAR T cells are unaltered after labeling with TAT nanoemulsion, and in vitro tumor cell killing assays display intact cytotoxic function. The 19F MRI signal detected from TAT‐labeled CAR T cells was 8 times higher than cells labeled with PFC without TAT. Conclusion: The peptide‐PFC nanoemulsion synthesis scheme presented can significantly enhance cell labeling and imaging sensitivity and is generalizable for other targeted imaging probes. [ABSTRACT FROM AUTHOR]

Fluorine-19 (19F) MRI is an emerging theranostic tool for studying diseases and treatments simultaneously, particularly in challenging neuroinflammatory conditions. However, the low signal-to-noise ratio (SNR) of 19F MRI necessitates computational methods to reliably detect 19F signal regions and segment these from the background. In this study, we demonstrate that Bayesian fully convolutional neural networks provide a means to increase sensitivity in 19F MRI and simultaneously provide estimates of data uncertainty. While our model effectively denoises the data, uncertain areas remain, particularly in boundary regions of the foreground. The uncertainty estimates are beneficial in preventing overconfident downstream analysis on noisy data and providing crucial information for rectifying prediction errors. Our results demonstrate that our model significantly outperforms other commonly used methods for 19F MRI signal detection in terms of sensitivity, while also providing valuable uncertainty estimates. • Fluorine-19 (19F) MRI is a promising tool for studying diseases and treatments. • Analysis of 19F MRI data necessitates detecting the 19F MRI signals from noise. • Current methods use background subtraction, but suffer from low sensitivity. • BDL enhances 19F MRI sensitivity significantly, generating reliable uncertainty maps. • Uncertainty maps aid 19F experts to analyze predictions, thus enhancing reliability. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of micro‐electromechanical systems (MEMS) switches against PIN diodes for switching a dual‐tuned RF coil between 19F and 1H resonant frequencies for multi‐nuclear lung imaging. Methods: A four‐element fixed‐phase and amplitude transmit–receive RF coil was constructed to provide homogeneous excitation across the lungs, and to serve as a test system for various switching methods. The MR imaging and RF performance of the coil when switched between the 19F and 1H frequencies using MEMS switches, PIN diodes and hardwired configurations were compared. Results: The performance of the coil with MEMS or PIN diode switching was comparable in terms of RF measurements, transmit efficiency and image SNR on both 19F and 1H nuclei. When the coil was not switched to the resonance frequency of the respective nucleus being imaged, reductions in the transmit efficiency were observed of 32% at the 19F frequency and 12% at the 1H frequency. The coil provides transmit field homogeneity of ±12.9% at the 1H frequency and ±14.4% at the 19F frequency in phantoms representing the thorax with the air space of the lungs filled with perfluoropropane gas. Conclusion: MEMS and PIN diodes were found to provide comparable performance in on‐state configuration, while MEMS were more robust in off‐state high‐powered operation (>1 kW), providing higher isolation and requiring a lower DC switching voltage than is needed for reverse biasing of PIN diodes. In addition, clear benefits of switching between the 19F and 1H resonances were demonstrated, despite the proximity of their Larmor frequencies. [ABSTRACT FROM AUTHOR]

Highlights: [•] R1 of perfluoropolyethers can be explained by dipole–dipole interactions and CSA. [•] Molecular motion determines the differences in R1 between PCE and PFPE. [•] The rotational correlation time of PFPE was estimated from R1 versus temperature plots. [Copyright &y& Elsevier]

Fluorine-19 magnetic resonance imaging (19F MRI) could be a promising approach for imaging amyloid deposition in the brain. However, the required features of a 19F MRI probe for amyloid detection remain unclear. In the present study, we investigated a series of compounds as potent 19F probes that could prevent the reduction in MR signal when bound to amyloid plaques in the brain. Each compound consists of styrylbenzoxazole as a core structure linked by a different length of polyethylene glycol (PEG) chain to one of three types of fluorine-labeled group: a trifluoroethoxy group, a hexafluoroisopropoxy group, or a 3′,5′-bis(trifluoromethyl)benzylamino group. Among these compounds, 6-(3′,6′,9′,15′,18′,21′-heptaoxa-23′,23′,23′-trifluoro tricosanyloxy)-2-(4′-dimethylaminostyryl)benzoxazole [compound 3b (m = 6)], which has a trifluoroethoxy group with seven ethylene glycol groups in the PEG chain, showed significant 19F MR signals in the brains of AβPPswe/PS1dE9 double-transgenic mice, but not wild-type mice. This suggested that compound 3b (m = 6) could be a useful 19F MRI probe for amyloid detection. Furthermore, this study identified the most effective length of PEG chain between the fluorine-labeled group and the core structure to ensure a strong MR signal when the probe is bound to amyloid plaques. [ABSTRACT FROM AUTHOR]

Cell tracking using perfluorocarbon labels and fluorine-19 (19F) MRI is a noninvasive approach to visualize and quantify cell populations in vivo. In this study, we investigated three-dimensional compressed sensing methods to accelerate 19F MRI data acquisition for cell tracking and evaluate the impact of acceleration on 19F signal quantification. We show that a greater than 8-fold reduction in imaging time was feasible without pronounced image degradation and with minimal impact on the image signal-to-noise ratio and 19F quantification accuracy. In 19F phantom studies, we show that apparent feature topology is maintained with compressed sensing reconstruction, and false positive signals do not appear in areas devoid of fluorine. We apply the three-dimensional compressed sensing 19F MRI methods to quantify the macrophage burden in a localized wounding-inflammation mouse model in vivo; at 8-fold image acceleration, the 19F signal distribution was accurately reproduced, with no loss in signal-to-noise ratio. Our results demonstrate that three-dimensional compressed sensing methods have potential for advancing in vivo 19F cell tracking for a wide range of preclinical and translational applications. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To firstly improve the attainable image SNR of 19 F and 1 H C 3 F 8 lung imaging at 1.5 tesla using an 8-element transmit/receive (Tx/Rx) flexible vest array combined with a 6-element Rx-only array, and to secondly evaluate microelectromechanical systems for switching the array elements between the 2 resonant frequencies., Methods: The Tx efficiency and homogeneity of the 8-element array were measured and simulated for 1 H imaging in a cylindrical phantom and then evaluated for in vivo 19 F/ 1 H imaging. The added improvement provided by the 6-element Rx-only array was quantified through simulation and measurement and compared to the ultimate SNR. It was verified through the measurement of isolation that microelectromechanical systems switches provided broadband isolation of Tx/Rx circuitry such that the 19 F tuned Tx/Rx array could be effectively used for both 19 F and 1 H nuclei., Results: For 1 H imaging, the measured Tx efficiency/homogeneity (mean ± percent SD; 6.79 μ T / kW ± 26 % ) was comparable to that simulated ( 7.57 μ T / kW ± 20 % ). The 6 additional Rx-only loops increased the mean Rx sensitivity when compared to the 8-element array by a factor of 1.41× and 1.45× in simulation and measurement, respectively. In regions central to the thorax, the simulated SNR of the 14-element array achieves ≥70% of the ultimate SNR when including noise from the matching circuits and preamplifiers. A measured microelectromechanical systems switching speed of 12 µs and added minimum 22 dB of isolation between Tx and Rx were sufficient for Tx/Rx switching in this application., Conclusion: The described single-tuned array driven at 19 F and 1 H, utilizing microelectromechanical systems technology, provides excellent results for 19 F and 1 H dual-nuclear lung ventilation imaging., (© 2020 International Society for Magnetic Resonance in Medicine.)

The two main challenges that prevent the translation of fluorine‐19 (19F) MRI for inflammation monitoring or cell tracking into clinical practice are (i) the relatively low signal‐to‐noise ratio generated by the injected perfluorocarbon (PFC), which necessitates long scan times, and (ii) the need for regulatory approval and a high biocompatibility of PFCs that are also suitable for MRI. ABL‐101, an emulsion of perfluoro(t‐butylcyclohexane), is a third‐generation PFC that is already used in clinical trials, but has not yet been used for 19F MRI. The objective of this study was therefore to assess the performance of ABL‐101 as a 19F MRI tracer. At magnetic field strengths of 3, 9.4 and 14.1 T, the CF3 groups of ABL‐101 generated a large well‐separated singlet with T2/T1 ratios of >0.27, >0.14 and > 0.05, respectively. All relaxation times decreased with the increase in magnetic field strength. The detection limit of ABL‐101 in a 0.25 mm3 voxel at 3 T, 37°C and with a 3‐minute acquisition time was 7.21mM. After intravenous injection, the clearance half‐lives of the ABL‐101 19F MR signal in mouse (n = 3) spleen and liver were 6.85 ± 0.45 and 3.20 ± 0.35 days, respectively. These results demonstrate that ABL‐101 has 19F MR characteristics that are similar to those of PFCs developed specifically for MRI, while it has clearance half‐lives similar to PFCs that have previously been used in large doses in non‐MRI clinical trials. Overall, ABL‐101 is thus a very promising candidate tracer for future clinical trials that use 19F MRI for cell tracking or the monitoring of inflammation. [ABSTRACT FROM AUTHOR]

Aggregation of tau into neurofibrillary tangles (NFTs) is characteristic of tauopathies, including Alzheimer's disease. Recent advances in tau imaging have attracted much attention because of its potential contributions to early diagnosis and monitoring of disease progress. Fluorine-19 magnetic resonance imaging ( 19 F-MRI) may be extremely useful for tau imaging once a high-quality probe has been formulated. In this investigation, a novel fluorine-19-labeling compound has been developed as a probe for tau imaging using 19 F-MRI. This compound is a buta-1,3-diene derivative with a polyethylene glycol side chain bearing a CF 3 group and is known as Shiga-X35. Female rTg4510 mice (a mouse model of tauopathy) and wild-type mice were intravenously injected with Shiga-X35, and magnetic resonance imaging of each mouse's head was conducted in a 7.0-T horizontal-bore magnetic resonance scanner. The 19 F-MRI in rTg4510 mice showed an intense signal in the forebrain region. Analysis of the signal intensity in the forebrain region revealed a significant accumulation of fluorine-19 magnetic resonance signal in the rTg4510 mice compared with the wild-type mice. Histological analysis showed fluorescent signals of Shiga-X35 binding to the NFTs in the brain sections of rTg4510 mice. Data collected as part of this investigation indicate that 19 F-MRI using Shiga-X35 could be a promising tool to evaluate tau pathology in the brain., (© 2017 Wiley Periodicals, Inc.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra projecting to the striatum. It has been estimated that approximately 80% of the striatal dopamine and 50% of nigral dopaminergic neurons are lost before the onset of typical motor symptoms, indicating that early diagnosis of PD using noninvasive imaging is feasible. Fluorine-19 ( 19 F) magnetic resonance imaging (MRI) represents a highly sensitive, easily available, low-background, and cost-effective approach to evaluate dopaminergic function using non-radioactive fluorine-containing dopaminergic agents. The aim of this study was to find a potent 19 F MRI probe to evaluate dopaminergic presynaptic function in the striatum. To select candidates for 19 F MRI probes, we investigated the following eight non-radioactive fluorine-containing dopaminergic agents: fluorodopa (F-DOPA), F-tyrosine, haloperidol, GBR13069 duhydrochloride, GBR12909 duhydrochloride, 3-bis-(4-fluorophenyl) methoxytropane hydrochloride, flupenthixol, and fenfluramine. In 19 F nuclear magnetic resonance measurements, F-tyrosine and F-DOPA displayed a relatively higher signal-to-noise ratio value in brain homogenates than in others. F-DOPA, but not F-tyrosine, induced the rotational behavior in a 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rat model. In addition, a significantly high amount of F-DOPA accumulated in the ipsilateral striatum of hemiparkinsonian rats after the injection. We performed 19 F MRI in PC12 cells and isolated rat brain using a 7T MR scanner. Our findings suggest that F-DOPA is a promising 19 F MRI probe for evaluating dopaminergic presynaptic function in the striatum of hemiparkinsonian rats. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)