Unstable atherosclerotic plaques exhibit microdeposits of fibrin that may indicate the potential for a future rupture. However, current methods for evaluating the stage of an atherosclerotic lesion only involve characterizing the level of vessel stenosis, without delineating which lesions are beginning to rupture. Previous work has shown that fibrin-targeted, liquid perfluorocarbon nanoparticles, which carry a high payload of gadolinium, have a high sensitivity and specificity for detecting fibrin with clinical 1 H MRI. In this work, the perfluorocarbon content of the targeted nanoparticles is exploited for the purposes of 19 F imaging and spectroscopy to demonstrate a method for quantifiable molecular imaging of fibrin in vitro at 4.7 T. Additionally, the quantity of bound nanoparticles formulated with different perfluorocarbon species was calculated using spectroscopy. Results indicate that the high degree of nanoparticle binding to fibrin clots and the lack of background 19 F signal allow accurate quantification using spectroscopy at 4.7 T, as corroborated with proton relaxation rate measurements at 1.5 T and trace element (gadolinium) analysis. Finally, the extension of these techniques to a clinically relevant application, the evaluation of the fibrin burden within an ex vivo human carotid endarterectomy sample, demonstrates the potential use of these particles for uniquely identifying unstable atherosclerotic lesions in vivo.

The combination of sensitive magnetic resonance techniques with a selective site-targeted nanoparticle contrast agent has a demonstrated utility for molecular imaging studies. By detecting a unique signature of the contrast agent, this approach can be employed to identify specific bio-molecular markers and observe cellular-level processes within a large and complex organism (e.g., in vivo rabbit). The objective of the present investigation was to design, fabricate and characterize a radio-frequency (RF) coil for the dual frequency (1H and 19F) simultaneous collection of both nuclei images in a 3T field, in order to facilitate studies of arthritic knee degradation in rabbits. The coil supports both transmit and receive modes. The supporting activities included: 1) establishing a technical database for calculating the required coil parameters, 2) selection of a favorable coil geometry, and 3) adaption of existing RF measurement techniques to the design, development and electrical evaluation of the coil. The coil is used in conjunction with a Philips Medical Systems clinical MRI scanner, requiring all RF simultaneous dual frequency (1H and 19F) coils to operate in both transmit and receive modes. A commercial version of SPICE (simulation program with integrated circuit emphasis) was used to estimate significant operational parameters prior to fabricating the imaging coil. Excellent images were obtained with the fabricated coil and no operational problems were observed that would limit the use of other coil geometries and field strengths.

Recent advances in the design of fluorinated nanoparticles for molecular magnetic resonance imaging (MRI) have enabled specific detection of 19 F nuclei, providing unique and quantifiable spectral signatures. However, a pressing need for signal enhancement exists because the total 19 F in imaging voxels is often limited. By directly incorporating a relaxation agent, gadolinium (Gd), into the lipid monolayer that surrounds the perfluorocarbon (PFC), a marked augmentation of the 19 F signal from 200-nm nanoparticles was achieved. This design increases the magnetic relaxation rate of the 19 F nuclei fourfold at 1.5 T and effects a 125% increase in signal-an effect that is maintained when they are targeted to human plasma clots. By varying the surface concentration of Gd, the relaxation effect can be quantitatively modulated to tailor particle properties. This novel strategy dramatically improves the sensitivity and range of 19

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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.