High-Contrast and Fast-Removable 19 F-MRI Labels with Perfluoro-tert-Butyl Substituents.

19 F MRI is a unique technique for tracking and quantifying the indicator (19 F-MRI label) in vivo without the use of ionizing radiation. Here we report new 19 F-MRI labels, which are compounds with perfluoro-tert-butyl groups: 1,2-bis(perfluoro-tert-butoxy)ethane (C10 F18 H4 O2 ) and 1,3-bis(perfluoro-tert-butyl)propane (C11 F18 H6 ). Both substances contain 18 equivalent 19 F atoms, constituting 68.67 % and 71.25 % of the molecule, respectively. The emulsions with 19 F molecules were prepared and used in 19 F MRI studies in laboratory rats in vivo. The substances demonstrated high contrast properties, good biological inertness and the ability to be rapidly eliminated from the body. We showed that at a dose of 0.34 mg/g of body weight in rats, the time for complete elimination of C10 F18 H4 O2 and C11 F18 H6 is ∼30 days. The results turned out to be promising for the use of the presented compounds in 19 F MRI applications, especially since they are quite easy to synthesize.

Т1 mapping of rat lungs in 19 F MRI using octafluorocyclobutane.

PURPOSE: To demonstrate the feasibility of using octafluorocyclobutane (OFCB, c-C4 F8 ) for T1 mapping of lungs in 19 F MRI. METHODS: The study was performed at 7 T in three healthy rats and three rats with pulmonary hypertension. To increase the sensitivity of 19 F MRI, a bent-shaped RF coil with periodic metal strips structure was used. The double flip angle method was used to calculate normalized transmitting RF field (B1n + ) maps and for correcting T1 maps built with the variable flip angle (VFA) method. The ultrashort TE pulse sequence was applied for acquiring MR images throughout the study. RESULTS: The dependencies of OFCB relaxation times on its partial pressure in mixtures with oxygen, air, helium, and argon were obtained. T1 of OFCB linearly depended on its partial pressure with the slope of about 0.35 ms/kPa in the case of free diffusion. RF field inhomogeneity leads to distortion of T1 maps built with the VFA method, and therefore to high standard deviation of T1 in these maps. To improve the accuracy of the T1 maps, the B1n + maps were applied for VFA correction. This contributed to a 2-3-fold decrease in the SD of T1 values in the corresponding maps compared with T1 maps calculated without the correction. Three-dimensional T1 maps were obtained, and the mean T1 in healthy rat lungs was 35 ± 10 ms, and in rat lungs with pulmonary hypertension - 41 ± 9 ms. CONCLUSION: OFCB has a spin-rotational relaxation mechanism and can be used for 19 F T1 mapping of lungs. The calculated OFCB maps captured ventilation defects induced by edema.

19 F MRI of human lungs at 0.5 Tesla using octafluorocyclobutane.

PURPOSE: The aim of this study was to demonstrate the feasibility of fluorine-19 (19 F) MRI of the human lungs using octafluorocyclobutane (OFCB, C4 F8 ). This gas has 8 magnetically equivalent fluorine nuclei and relatively long T1 and T2 (˜50 ms), which render it suitable as an MRI contrast agent. Previous experiments in small laboratory animals showed that OFCB could be successfully used as an alternative to the gases often used for 19 F MRI (sulfur hexafluoride and perfluoropropane). METHODS: One male volunteer participated in this study. Immediately before an MRI scan, the volunteer inhaled the gas mixture-80% OFCB with 20% oxygen-and held his breath. Experiments were performed on a 0.5T whole-body MR scanner with a customized transmit-receive coil tuned at 19 F frequency. Fast spin echo in 2D and 3D modes was used for image acquisition. 2D images were obtained with in-plane resolution of 10 × 10 mm2 without slice selection. 3D images were obtained with the voxel size of 10 × 10 × 30 mm2 . Breath-hold duration was 20 s for 2D and 40 s for 3D imaging, respectively. RESULTS: Anatomically consistent 19 F MR images of the human lungs were obtained with SNR around 50 in 2D mode and 20 in 3D mode. 3D volumetric images of the lungs were reconstructed and provided physiologically reasonable volume estimates. CONCLUSION: The application of OFCB enables informative 19 F lung imaging even at low magnetic field strengths. The OFCB gas shows promise as an inhalable contrast agent for fluorine lung MRI and has a potential for clinical translation.

Realization of 19F MRI oximetry method using perfluorodecalin.

OBJECTIVE: To identify the technical aspects of the potential use of clinically approved perfluorodecalin (PFD, C10F18) for 19F magnetic resonance imaging (MRI) oximetry method at high magnetic field 7.05 T. MATERIALS AND METHODS: 19F T1 measurements were made on a set of PFD samples with different oxygen contents (0%, 21%, and 100%) at room (21 °C) and body temperature (37 °C). In vivo MRI studies were carried out on one healthy rat and two rats with C6 brain glioma. RESULTS: The selective excitation of the magnetically equivalent 19F nuclei of CF2 groups of trans-isomer of PFD, which give a doublet at a frequency of about - 140 ppm (in relation the chemical shift of trifluoroacetic acid, which is - 76.55 ppm) should be done for correct implementation of 19F MRI oximetry method. The amount of PFD equal to 30 µl is the optimal for obtaining reliable data on the measured T1 values. In this case, the standard deviation of T1 does not exceed 5%. In vivo MRI studies showed that the values of the partial pressure of oxygen (pO2) decrease from normal values of about 38 mmHg (healthy brain) to almost 0 mmHg at the last stage of tumor growth. CONCLUSION: The study showed the feasibility of the successful application of PFD for 19F MRI oximetry method.