Cell tracking using 19F magnetic resonance imaging: Technical aspects and challenges towards clinical applications

Abstract

(19)F MRI is emerging as a new imaging technique for cell tracking. It is particularly attractive because of its potential for direct and precise cell quantification. The most important challenge towards in vivo applications is the sensitivity of the technique, i.e. the detection limit in a reasonable imaging time. Optimal sensitivity can be achieved with dedicated (19)F compounds together with specifically adapted hardware and acquisition methods. In this paper we introduce the (19)F MRI technique focusing on these key sensitivity issues and review the state-of-the-art of (19)F MRI and developments towards its clinical use. We calculate (19)F detection limits reported in preclinical cell and clinical (19)F drug studies in terms of tissue concentration in a 1 cm(3) voxel, as an alternate way to compare detection limits. We estimate that a tissue concentration of a few millimoles per litre (mM) of (19)F is required for a human study at a resolution of 1 cm(3).

In vivo and ex vivo 19‐fluorine magnetic resonance imaging and spectroscopy of beta‐cells and pancreatic islets using GLUT‐2 specific contrast agents

“…In general, for reliable detection a threshold of approximately 10 16 fluorine spins/voxel is considered (one hour acquisition time at 9.4 T) (16). For this study, the in vivo detection limit of our home built surface coil was approximately 5*10 15 19 F spins/ voxel, which is comparable to previous work for performing 19 F MRI.…”

“…Within the same transverse plane, this coil exhibits good linear relationships (Y = 0.67X + 2) between the SNR and the concentration of 19 F spins as shown in Figure 2B, which is essential for the quantification of the fluorinated compounds and ultimately for the quantification of the number of cells. The detection limit for 19 F MRI is approximately 5*10 15 F spins/pixel using a gradient echo 3D sequence with 120 averages and a similar repetition time of 1 s, which is in a similar range (10 15 -10 16 ) as described in the literature (16,17 19 FMH by isolated islets. Considering an islet diameter of 200 to 400 μm (18,19), the intra-islet concentration averages 0.5 to 4 M after overnight incubation of islets at 37°C in the presence of 15 mM of [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] FMH (see also Figure 3).…”

Nanoparticles and clinically applicable cell tracking

“…These involve efforts to increase cellular uptake by probe modifications or the use of transfection agents that promote cellular uptake of particles, [91][92][93] probe modifications that increase the signalling capacity per molecule, 94,95 and hardware and software developments. 37 …”

Visualization of delayed release of compounds from pH‐sensitive capsules in vitro and in vivo in a hamster model

“…This can be overcome by the use of 19 F-containing contrast agents. These have been shown to be complementary to the acquisition of traditional proton-based, anatomical images ( 1 H-MRI) (20). Due to the lack of MR-detectable 19 F signal inside biological tissues, all signal from 19 F-MRI originates from the (dissolved) contrast agent, which makes the technique very specific and quantifiable (21).…”