Fluorine Cardiovascular Magnetic Resonance Angiography In Vivo at 1.5 T with Perfluorocarbon Nanoparticle Contrast Agents

Abstract

While the current gold standard for coronary imaging is X-ray angiography, evidence is accumulating that it may not be the most sensitive technique for detecting unstable plaque. Other imaging modalities, such as cardiovascular magnetic resonance (CMR), can be used for plaque characterization, but suffer from long scan and reconstruction times for determining regions of stenosis. We have developed an intravascular fluorinated contrast agent that can be used for angiography with cardiovascular magnetic resosnace at clinical field strengths (1.5 T). This liquid perfluorocarbon nanoparticle contains a high concentration of fluorine atoms that can be used to generate contrast on 19F MR images without any competing background signal from surrounding tissues. By using a perfluorocarbon with 20 equivalent fluorine molecules, custom-built RF coils, a modified clinical scanner, and an efficient steady-state free procession sequence, we demonstrate the use of this agent for angiography of small vessels in vitro, ex vivo, and in vivo. The surprisingly high signal generated with very short scan times and low doses of perfluorocarbon indicates that this technique may be useful in clinical settings when coupled with advanced imaging strategies.

Liquid Perfluorocarbons as Contrast Agents for Ultrasonography and 19F-MRI

“…By their specific binding and local accumulation, nanoemulsions demonstrated that the limited concentrations at the pathological site and the possible weakness of the fluorine signal as compared with proton can be overcome. Following these results, nonbiotinylated nanoemulsions of PFCE were also used as contrast agent for angiography with cardiovascular magnetic resonance at clinical strength (99). The high level of signal (109) obtained for nanoemulsions on 19 F MR images allowed for applying this system for angiography of small vessels in vitro, ex vivo on pig hearts for detecting coronary vessels and in vivo on rabbits after injection into carotid arteries.…”

Clinical Perspectives of Hybrid Proton-Fluorine Magnetic Resonance Imaging and Spectroscopy

“…In addition, a high level of background signal can be present because of the fast extravasation of the lowYmolecular-weight CAs, which can be avoided only by fast image acquisition. 71 71 showed that fluorineenhanced angiography of rabbits is feasible on a clinical 1.5-T MR system (Fig. 4).…”

Perfluorocarbon Nanoparticles for Physiological and Molecular Imaging and Therapy

“…45 In the case of 19 F imaging, quantification of the amount of PFC NP in the imaging field of view is possible by directly assessing the spectral energy contained within the 19 F readout, which is proportional to the 19 F concentration, and thus the number of PFC NP containing them. 46–49 Thus, the non-targeted PFC NP agents have been developed for blood pool imaging and perfusion, 46–48, 50 cellular (stem cell, dendritic cell, etc.) labeling and tracking, 49, 51–55 cellular and tissue uptake for imaging inflammation and allograft rejection, among others.…”

“…50 Given the high blood volume in the kidney and the availability of 3T clinical MR consoles, 19 F MRI assessment of kidney blood volume and pO 2 should be achievable in clinical settings.…”