Gadolinium‐modulated ¹⁹F signals from perfluorocarbon nanoparticles as a new strategy for molecular imaging

Abstract

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

19F‐lanthanide complexes with increased sensitivity for 19F‐MRI: Optimization of the MR acquisition

“…A limited number of previous studies have also considered incorporating relaxation agents to increase imaging sensitivity. Neubauer et al (14) incorporated gadolinium ions into a lipid monolayer which was used to package perfluorocarbon emulsion and achieved a 4-fold increase in R 1 at 1.5 T (values typically between 2 and 6 s À1 ) with a resulting increase in imaging sensitivity of 125%. This improvement in relaxation rate is very modest compared with the approach demonstrated here which offers a further order of magnitude increase in R 1 .…”

“…Second, as examined here, modifying the molecular NMR relaxation properties can potentially be used to enhanced detection. Compartmentalization of 19 F labeled molecules with standard gadolinium agents, for example, within lipid emulsions, has been shown to decrease 19 F T 1 , allowing rapid pulsing [shorter, pulse repetition time (TR)] and increasing signal-to-noise per unit time (14).…”

Design of protein homocystamides with enhanced tumor uptake properties for 19F magnetic resonance imaging

“…[36][37][38][39][40][41] Emulsions and nano-systems encapsulating liquid perfluorocarbons (PFCs) as contrast agents for MRI have proven their potentialities for the imaging of blood pool, ventricular abnormalities, liver, thrombi, atherosclerosis, mononuclear phagocyte system, tumor, molecular imaging of angiogenesis and drug delivery carriers of anticancer drugs. However, the use of PFC emulsions is limited due to their heterogeneity, instability, split 19 F signals, as well as excessive retention within internal organs (liver, spleen, lung) for a prolonged period of time.…”

A generalized strategy for designing 19F/1H dual‐frequency MRI coil for small animal imaging at 4.7 Tesla

“…A 50-mL tube filled with saline and 10% perfluoro-15-crown-5-ether (CE) emulsion was imaged with a gradient echo sequence. The formulated CE emulsion is composed of 20% (or 40%) (v/v) of CE (Exfluor Research Corp., USA), 2.0% (w/v) of a surfactant commixture, and 1.7% (w/v) glycerin, with water comprising the balance (21).…”

“…All coils achieved impedance matching at both 1 Figure 3 shows the B1 field distribution, measured from corresponding coupling intensity in S 21 , of the birdcage coil and saddle coil working at both 19 F and 1 H frequencies. For the birdcage coil, the fluctuation of magnetic field strength was less than 10% for > 60% area in radial direction and > 75% of area in axial direction (Fig.…”