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

Abstract

Background MRI with fluorine 19 (¹⁹F) 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 ¹⁹F probes make dual-probe imaging possible. To improve ¹⁹F MRI sensitivity for dual-probe imaging, optimal fluorine probes are needed. Purpose To develop multispectral ¹⁹F MRI to image immune cell activity in vivo using ¹⁹F nanoparticles of two distinct fluorocarbons. Materials and Methods Both ¹⁹F 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. ¹⁹F 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 ¹⁹F nanoparticles to allow flow-cytometric and confocal microscopy analysis of labeled cells. Fluorine signal-to-noise 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 ¹⁹F 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 ¹⁹F nanoparticles, MRI with dual ¹⁹F probes can effectively track immune cell activity in combination with current MRI protocols. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Bulte in this issue.