Fluorine-19 Magnetic Resonance Angiography of the Mouse

Abstract

PurposeTo implement and characterize a fluorine-19 (19F) magnetic resonance imaging (MRI) technique and to test the hypothesis that the 19F MRI signal in steady state after intravenous injection of a perfluoro-15-crown-5 ether (PCE) emulsion may be exploited for angiography in a pre-clinical in vivo animal study.Materials and Methods In vitro at 9.4T, the detection limit of the PCE emulsion at a scan time of 10 min/slice was determined, after which the T1 and T2 of PCE in venous blood were measured. Permission from the local animal use committee was obtained for all animal experiments. 12 µl/g of PCE emulsion was intravenously injected in 11 mice. Gradient echo 1H and 19F images were obtained at identical anatomical levels. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were determined for 33 vessels in both the 19F and 1H images, which was followed by vessel tracking to determine the vessel conspicuity for both modalities.Results In vitro, the detection limit was ∼400 µM, while the 19F T1 and T2 were 1350±40 and 25±2 ms. The 19F MR angiograms selectively visualized the vasculature (and the liver parenchyma over time) while precisely coregistering with the 1H images. Due to the lower SNR of 19F compared to 1H (17±8 vs. 83±49, p<0.001), the 19F CNR was also lower at 15±8 vs. 52±35 (p<0.001). Vessel tracking demonstrated a significantly higher vessel sharpness in the 19F images (66±11 vs. 56±12, p = 0.002).Conclusion 19F magnetic resonance angiography of intravenously administered perfluorocarbon emulsions is feasible for a selective and exclusive visualization of the vasculature in vivo.

Temporal accumulation and localization of isoflurane in the C57BL/6 mouse and assessment of its potential contamination in 19F MRI with perfluoro‐crown‐ether‐labeled cardiac progenitor cells at 9.4 Tesla

“…ISO exhibited chemical shifts of ‐4.0 (CF 3 ) and ‐10.3 ppm (‐OCHF 2 ) in C57BL/6 mice in vivo with respect to the TFA resonance at 0 ppm, confirming previous reports in rabbits, and C57BL/6 and BALB/c mice . The downfield shift of ISO in vivo has been attributed to the chemical structure and the microenvironment in which ISO resides .…”

“…Two distinct ISO resonances are observed in vivo (Fig. D) that, respectively, correspond to the ‐CF 3 , and ‐OCHF 2 moieties . Noted also is a downfield spectral shift of the ISO resonances in vivo by approximately ‐4 ppm, and an increase in the spectral linewidth of the ‐CF 3 peak to 500 Hz.…”

“…The scope of this study is generalized on the accumulation of ISO (in striated skeletal and cardiac muscles). It extends beyond the two prominent prior 19 F MRS/MRI publications that focused on cardiovascular applications, whereby direct injections of labeled emulsions were achieved by means of the intravenous route. Their reported approach exhibits bio‐distribution, delivery, temporal dynamics, and label dilution differences, compared with current state‐of‐the‐art schemes using either direct injections (adopted strategy in this study), or scaffold‐based, 19 F labeled, cardiac progenitor stem cell administrations.…”

Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla

“…The detection limits reported here are furthermore up to several orders of magnitude below the 19 F tissue concentrations (∼6 M) that have been reported previously . Finally, the detection limit of PFCE with a gradient echo (GRE) pulse sequence was determined with a small surface coil at 9.4T , which resulted in a detection limit of 0.5 mM when normalized as in the present study, demonstrating the increase in signal sensitivity when using a small surface coil and higher magnetic field strengths.…”

In vivo MRI cell tracking using perfluorocarbon probes and fluorine‐19 detection

“…Pulse sequences with an intrinsically-high SNR per image acquisition time are generally preferred, such as RARE (56,57), SSFP (14,55), GRE (72,73), and EPI (74,75). These sequences may be combined with parallel imaging techniques (76,77) to further reduce the total imaging acquisition time.…”