Feasibility and optimization of19F MRI on a clinical 3T with a large field-of-view torso coil.

Objective.The objective of this work is to: (1) demonstrate fluorine-19 (19F) MRI on a 3T clinical system with a large field of view (FOV) multi-channel torso coil (2) demonstrate an example parameter selection optimization for a19F agent to maximize the signal-to-noise ratio (SNR)-efficiency for spoiled gradient echo (SPGR), balanced steady-state free precession (bSSFP), and phase-cycled bSSFP (bSSFP-C), and (3) validate detection feasibility inex vivotissues.Approach.Measurements were conducted on a 3.0T Discovery MR750w MRI (GE Healthcare, USA) with an 8-channel1H/19F torso coil (MRI Tools, Germany). Numerical simulations were conducted for perfluoropolyether to determine the theoretical parameters to maximize SNR-efficiency for the sequences. Theoretical parameters were experimentally verified, and the sensitivity of the sequences was compared with a 10 min acquisition time with a 3.125 × 3.125 × 3 mm3in-plane resolution. Feasibility of a bSSFP-C was also demonstrated in phantom andex vivotissues.Main Results. Flip angles (FAs) of 12 and 64° maximized the signal for SPGR and bSSFP, and validation of optimal FA and receiver bandwidth showed close agreement with numerical simulations. Sensitivities of 2.47, 5.81, and 4.44ms-0.5mM-1 and empirical detection limits of 20.3, 1.5, and 6.2 mM were achieved for SPGR, bSSFP, and bSSFP-C, respectively. bSSFP and bSSFP-C achieved 1.8-fold greater sensitivity over SPGR (p< 0.01).Significance.bSSFP-C was able to improve sensitivity relative to simple SPGR and reduce both bSSFP banding effects and imaging time. The sequence was used to demonstrate the feasibility of19F MRI at clinical FOVs and field strengths withinex-vivotissues.

Utilization of 19F MRI for Identification of Iraq-Afghanistan War Lung Injury.

INTRODUCTION: There is mounting evidence of respiratory problems related to military service in the Middle East in the past two decades due to environmental exposures during deployment (eg, sand storms and burn pits). This pilot study tests the hypothesis that regional lung function in subjects with prior deployment in Iraq and/or Afghanistan with suspected War Lung Injury (WLI) would be worse than subjects with normal lung function. MATERIALS AND METHODS: Five subjects meeting the inclusion and exclusion criteria were recruited for this pilot study. All subjects underwent spirometry, high-resolution chest computed tomography imaging, and 19F MRI. RESULTS: While the WLI subjects had normal pulmonary function tests and normal high-resolution chest computed tomography evaluations, their regional lung function from 19F MRI was abnormal with compartments with poor function showing slower filling time constants for ventilation. The scans of suspected WLI subjects show higher fractional lung volume with slow filling compartments similar to patients with chronic obstructive pulmonary disease in contrast to normal subjects. CONCLUSIONS: This is consistent with our premise that WLI results in abnormal lung function and reflects small airways dysfunction and suggests that we may be able to provide a more sensitive tool for evaluation of WLI suspected cases.

Towards Quantification of Inflammation in Atherosclerotic Plaque in the Clinic - Characterization and Optimization of Fluorine-19 MRI in Mice at 3 T.

Fluorine-19 (19F) magnetic resonance imaging (MRI) of injected perfluorocarbons (PFCs) can be used for the quantification and monitoring of inflammation in diseases such as atherosclerosis. To advance the translation of this technique to the clinical setting, we aimed to 1) demonstrate the feasibility of quantitative 19F MRI in small inflammation foci on a clinical scanner, and 2) to characterize the PFC-incorporating leukocyte populations and plaques. To this end, thirteen atherosclerotic apolipoprotein-E-knockout mice received 2 × 200 µL PFC, and were scanned on a 3 T clinical MR system. 19F MR signal was detected in the aortic arch and its branches in all mice, with a signal-to-noise ratio of 11.1 (interquartile range IQR = 9.5-13.1) and a PFC concentration of 1.15 mM (IQR = 0.79-1.28). Imaging flow cytometry was used on another ten animals and indicated that PFC-labeled leukocytes in the aortic arch and it branches were mainly dendritic cells, macrophages and neutrophils (ratio 9:1:1). Finally, immunohistochemistry analysis confirmed the presence of those cells in the plaques. We thus successfully used 19F MRI for the noninvasive quantification of PFC in atherosclerotic plaque in mice on a clinical scanner, demonstrating the feasibility of detecting very small inflammation foci at 3 T, and advancing the translation of 19F MRI to the human setting.

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.

Towards Ni(II) complexes with spin switches for 19F MR-based pH sensing.

OBJECTIVES: Our aim was to demonstrate the potential of exploiting simultaneous changes in coordination geometry and spin state in fluorinated Ni(II) complexes as an avenue for 19F magnetic-resonance (MR)-based pH sensing. MATERIALS AND METHODS: Crystal structures were studied using an Agilent Technologies SuperNova Dual Source diffractometer. Solution magnetic moment was determined using Evan's method. MR images were collected on a 7.0-T MR scanner equipped with a quadrature 19F volume coil. RESULTS: NiL1 and NiL2 were synthesized; crystallographic and spectroscopic data supported NiL1 as being diamagnetic and NiL2 as being paramagnetic. In aqueous solution, ligand dissociation from Ni(II) center was observed for both complexes at around pH 6, precluding their use as reversible pH sensors. The two complexes have distinct 19F nuclear magnetic resonance (NMR) signals in terms of both chemical shift and relaxation times, and selective imaging of the two complexes was achieved with no signal interference using two 19F MRI pulse sequences. CONCLUSION: The significant difference in the chemical shift and relaxation times between NiL1 and NiL2 allowed selective imaging of these species using 19F MRI. While NiL1 and NiL2 were not stable to acidic environments, this report lays the framework for development of improved ligand scaffolds that stably coordinate Ni(II) in acidic aqueous solution and act as agents for ratiometric pH mapping by 19F MRI.

Longitudinal 19F magnetic resonance imaging of brain oxygenation in a mouse model of vascular cognitive impairment using a cryogenic radiofrequency coil.

INTRODUCTION: We explored the use of a perfluoro-15-crown-5 ether nanoemulsion (PFC) for measuring tissue oxygenation using a mouse model of vascular cognitive impairment. METHODS: Seventeen C57BL/6 mice underwent stereotactic injection of PFC coupled to a fluorophore into the striatum and corpus callosum. Combined 1H/19F magnetic resonance imaging (MRI) to localize the PFC and R1 mapping to assess pO2 were performed. The effect of gas challenges on measured R1 was investigated. All mice then underwent bilateral implantation of microcoils around the common carotid arteries to induce global cerebral hypoperfusion. 19F-MRI and R1 mapping were performed 1 day, 1 week, and 4 weeks after microcoil implantation. In vivo R1 values were converted to pO2 through in vitro calibration. Tissue reaction to the PFC was assessed through ex vivo immunohistochemistry of microglial infiltration. RESULTS: R1 increased with increasing oxygen concentrations both in vitro and in vivo and the strength of the 19F signal remained largely stable over 4 weeks. In the two mice that received all four scans, tissue pO2 decreased after microcoil implantation and recovered 4 weeks later. We observed infiltration of the PFC deposits by microglia. DISCUSSION: Despite remaining technical challenges, intracerebrally injected PFC is suitable for monitoring brain oxygenation in vivo.

Toward 19F magnetic resonance thermometry: spin-lattice and spin-spin-relaxation times and temperature dependence of fluorinated drugs at 9.4 T.

OBJECTIVE: This study examines the influence of the environmental factor temperature on the 19F NMR characteristics of fluorinated compounds in phantom studies and in tissue. MATERIALS AND METHODS: 19F MR mapping and MR spectroscopy techniques were used to characterize the 19F NMR characteristics of perfluoro-crown ether (PFCE), isoflurane, teriflunomide, and flupentixol. T1 and T2 mapping were performed, while temperature in the samples was changed (T = 20-60 °C) and monitored using fiber optic measurements. In tissue, T1 of PFCE nanoparticles was determined at physiological temperatures and compared with the T1-measured at room temperature. RESULTS: Studies on PFCE, isoflurane, teriflunomide, and flupentixol showed a relationship between temperature and their physicochemical characteristics, namely, chemical shift, T1 and T2. T1 of PFCE nanoparticles was higher at physiological body temperatures compared to room temperature. DISCUSSION: The impact of temperature on the 19F NMR parameters of fluorinated compounds demonstrated in this study not only opens a trajectory toward 19F MR-based thermometry, but also indicates the need for adapting MR sequence parameters according to environmental changes such as temperature. This will be an absolute requirement for detecting fluorinated compounds by 19F MR techniques in vivo.

Comparison of MEMS switches and PIN diodes for switched dual tuned RF coils.

PURPOSE: To evaluate the performance of micro-electromechanical systems (MEMS) switches against PIN diodes for switching a dual-tuned RF coil between 19 F and 1 H 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 19 F and 1 H 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 19 F and 1 H 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 19 F frequency and 12% at the 1 H frequency. The coil provides transmit field homogeneity of ±12.9% at the 1 H frequency and ±14.4% at the 19 F 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 19 F and 1 H resonances were demonstrated, despite the proximity of their Larmor frequencies.

Eight-channel transceiver RF coil array tailored for ¹H/¹9F MR of the human knee and fluorinated drugs at 7.0 T.

The purpose of this study was to evaluate the feasibility of an eight-channel dual-tuned transceiver surface RF coil array for combined (1)H/(19)F MR of the human knee at 7.0 T following application of (19)F-containing drugs. The (1)H/(19)F RF coil array includes a posterior module with two (1)H loop elements and two anterior modules, each consisting of one (1)H and two (19)F elements. The decoupling of neighbor elements is achieved by a shared capacitor. Electromagnetic field simulations were performed to afford uniform transmission fields and to be in accordance with RF safety guidelines. Localized (19)F MRS was conducted with 47 and 101 mmol/L of flufenamic acid (FA) ­ a (19)F-containing non-steroidal anti-inflammatory drug ­ to determine T1 and T2 and to study the (19)F signal-to-dose relationship. The suitability of the proposed approach for (1)H/(19)F MR was examined in healthy subjects. Reflection coefficients of each channel were less than -17 dB and coupling between channels was less than -11 dB. Q(L)/Q(U) was less than 0.5 for all elements. MRS results demonstrated signal stability with 1% variation. T1 and T2 relaxation times changed with concentration of FA: T1 /T2 = 673/31 ms at 101 mmol/L and T1 /T2 = 616/26 ms at 47 mmol/L. A uniform signal and contrast across the patella could be observed in proton imaging. The sensitivity of the RF coil enabled localization of FA ointment administrated to the knee with an in-plane spatial resolution of (1.5 × 1.5) mm(2) achieved in a total scan time of approximately three minutes, which is well suited for translational human studies. This study shows the feasibility of combined (1)H/(19)F MRI of the knee at 7.0 T and proposes T1 and T2 mapping methods for quantifying fluorinated drugs in vivo. Further technological developments are necessary to promote real-time bioavailability studies and quantification of (19)F-containing medicinal compounds in vivo.

Balanced UTE-SSFP for 19F MR imaging of complex spectra.

PURPOSE: A novel technique for highly sensitive detection of multiresonant fluorine imaging agents was designed and tested with the use of dual-frequency 19F/1H ultrashort echo times (UTE) sampled with a balanced steady-state free precession (SSFP) pulse sequence and three-dimensional (3D) radial readout. METHODS: Feasibility of 3D radial balanced UTE-SSFP imaging was demonstrated for a phantom comprising liquid perfluorooctyl bromide (PFOB). Sensitivity of the pulse sequence was measured and compared with other sequences imaging the PFOB (CF2 )6 line group including UTE radial gradient-echo (GRE) at α = 30°, as well as Cartesian GRE, balanced SSFP, and fast spin-echo (FSE). The PFOB CF3 peak was also sampled with FSE. RESULTS: The proposed balanced UTE-SSFP technique exhibited a relative detection sensitivity of 51 µmolPFOB(-1) min(-1/2) (α = 30°), at least twice that of other sequence types with either 3D radial (UTE GRE: 20 µmolPFOB(-1) min(-1/2) ) or Cartesian k-space filling (GRE: 12 µmolPFOB(-1) min(-1/2) ; FSE: 16 µmolPFOB(-1) min(-1/2) ; balanced SSFP: 23 µmolPFOB(-1) min(-1/2) ). In vivo imaging of angiogenesis-targeted PFOB nanoparticles was demonstrated in a rabbit model of cancer on a clinical 3 Tesla scanner. CONCLUSION: A new dual 19F/1H balanced UTE-SSFP sequence manifests high SNR, with detection sensitivity more than two-fold better than traditional techniques, and alleviates imaging problems caused by dephasing in complex spectra.

Cell tracking using (19)F magnetic resonance imaging: technical aspects and challenges towards clinical applications.

(19)F MRI is emerging as a new imaging technique for cell tracking. It is particularly attractive because of its potential for direct and precise cell quantification. The most important challenge towards in vivo applications is the sensitivity of the technique, i.e. the detection limit in a reasonable imaging time. Optimal sensitivity can be achieved with dedicated (19)F compounds together with specifically adapted hardware and acquisition methods. In this paper we introduce the (19)F MRI technique focusing on these key sensitivity issues and review the state-of-the-art of (19)F MRI and developments towards its clinical use. We calculate (19)F detection limits reported in preclinical cell and clinical (19)F drug studies in terms of tissue concentration in a 1 cm(3) voxel, as an alternate way to compare detection limits. We estimate that a tissue concentration of a few millimoles per litre (mM) of (19)F is required for a human study at a resolution of 1 cm(3).

Design and evaluation of a novel trifluorinated imaging agent for assessment of bile acid transport using fluorine magnetic resonance imaging.

Previously, we developed a trifluorinated bile acid, CA-lys-TFA, with the objective of noninvasively assessing bile acid transport in vivo using (19) F magnetic resonance imaging (MRI). CA-lys-TFA was successfully imaged in the mouse gallbladder, but was susceptible to deconjugation in vitro by choloylglycine hydrolase (CGH), a bacterial bile acid deconjugating enzyme found in the terminal ileum and colon. The objective of the present study was to develop a novel trifluorinated bile acid resistant to deconjugation by CGH. CA-sar-TFMA was designed, synthesized, and tested for in vitro transport properties, stability, imaging properties, and its ability to differentially accumulate in the gallbladders of normal mice, compared with mice with known impaired bile acid transport (deficient in the apical sodium-dependent bile acid transporter, ASBT). CA-sar-TFMA was a potent inhibitor and substrate of ASBT and the Na(+) /taurocholate cotransporting polypeptide. Stability was favorable in all conditions tested, including the presence of CGH. CA-sar-TFMA was successfully imaged and accumulated at 16.1-fold higher concentrations in gallbladders from wild-type mice compared with those from Asbt-deficient mice. Our results support the potential of using MRI with CA-sar-TFMA as a noninvasive method to assess bile acid transport in vivo.

Double-tuned radiofrequency coil for (19)F and (1)H imaging.

We developed a double-tuned radiofrequency (RF) coil using a novel circuit method to double tune for fluorine-19 (19F) and 1H magnetic resonance imaging, whose frequencies are very close to each other. The RF coil consists of 3 parallel-connected series inductor capacitor circuits. A computer simulation for our double-tuned RF coil with a phantom demonstrated that the coil has tuned resonant frequency and high sensitivity for both 19F and 1H. Drug distribution was visualized at 7 tesla using this RF coil and a rat administered perfluoro 15-crown-5-ether emulsion. The double-tune RF coil we developed may be a powerful tool for 19F and 1H imaging.