Multispectral MRI with Dual Fluorinated Probes to Track Mononuclear Cell Activity in Mice

Background: MRI with fluorine 19 (F-19) probes has shown an ability to track immune cell activity with a specific, stable, and quantitative signal. In addition, the chemical shift differences of selected F-19 probes make dual-probe imaging possible. To improve F-19 MRI sensitivity for dual-probe imaging, optimal fluorine probes are needed. Purpose: To develop multispectral F-19 MRI to image immune cell activity in vivo using F-19 nanoparticles of two distinct fluorocarbons. Materials and Methods: Both F-19 nanoparticles formulated with two fluorocarbons with distinct resonance frequencies and a high fluorine payload were characterized in terms of size, stability, MR profile, and relaxation times at 7 T. F-19 MRI sensitivity was tested on labeling cells both in vitro and in vivo in C57BL/6 mice after conditional ablation of myeloid cells through the inhibition of colony-stimulating factor-1 receptor (CSF1Ri) to monitor the change of immune cells phagocytosis. Fluorine MRI data were acquired at the resonance frequency of each fluorocarbon by using a three-dimensional fast spin-echo sequence. Fluorescent dyes were also inserted into F-19 nanoparticles to allow flow-cytometric and confocal microscopy analysis of labeled cells. Fluorine signal-tonoise ratio (SNR) was compared by using two-way repeated measures analysis of variance with Bonferroni post hoc correction. Results: Fluorine MRI demonstrated high sensitivity and high specificity in the imaging of mononuclear cells both in vitro and in vivo. In combination with proton MRI, a map of F-19 nuclei from each fluorocarbon was obtained without overlaps or artifacts. In vitro cell viability was unchanged, and 8000 cells with a high SNR (>8) were detected. In vivo high fluorine signal was observed in the bone marrow (SNR > 15) immediately after CSF1Ri treatment interruption, which correlated with high uptake by neutrophils and monocytes at flow cytometry. Conclusion: By assessing in vivo MRI of mononuclear cell phagocytic ability with F-19 nanoparticles, MRI with dual F-19 probes can effectively track immune cell activity in combination with current MRI protocols. (c) RSNA, 2019