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

Abstract

RI provides unique insights into disease pathogenesis. For molecular and cellular MRI, several contrast agents, each with different ability to enhance water proton relaxivity, have been exploited, including gadolinium chelates, iron oxide particles, and a family of chemical shift saturation transfer contrast agents (1-3). More recently, interest in fluorine 19 ( 19 F) emulsions has grown because fluorine MR signal from soft tissues is absent, and emulsions of fluorocarbon are biocompatible agents (4). Therefore, 19 F MRI is being explored for several applications, including cell tracking (4-8), molecular sensing (9,10) and for imaging inflammation in various diseased models (11)(12)(13)(14)(15)(16). Furthermore, since the 19 F MRI signal is directly related to the number of fluorine atoms, labeled cells can be quantified and monitored for a long time. Importantly, 19 F signal from fluorocarbons does not disturb standard proton ( 1 H) MRI and does not need precontrast data acquisition.Multicolor 19 F MRI has been previously attempted (8,17,18) with the use of fluorocarbons with multiresonance frequencies from nonequivalent fluorine nuclei that induce image artifacts and considerably limit the sensitivity and specificity of fluorine signal (19).We propose the use of two fluorocarbons with two clearly distinct resonance frequencies and a high number of chemically equivalent fluorine nuclei suitable for multispectral 19 F MRI. In particular, both 19 F nanoparticles were used to differentiate the normal and enhanced activity of phagocytosis after temporary inhibition of the colony stimulating factor 1 receptor (CSF1R), a key regulator of mononuclear cell production, differentiation, migration, and activation (20). CSF1R inhibition has been reported to be effective for depleting macrophages and microglial cells, which are rapidly regenerated within a few days after treatment interruption (21) and with an increase of phagocytic activity (20). In our study, we aimed to follow this

Beyond Vessel Diameters: Non-invasive Monitoring of Flow Patterns and Immune Cell Recruitment in Murine Abdominal Aortic Disorders by Multiparametric MRI

“…Our approach can be further expanded by longitudinal multiplex 19 F MRI to visualize multiple cell types or targets (51)(52)(53)(54)(55)(56) and combined with parametric and functional MRI. T1 as well as T2 mapping, late gadolinium enhancement, or chemical exchange saturation transfer MRI could be carried out in parallel to 19 F MRI to obtain a comprehensive overview of the evoked immune response and development/progression of tissue damage over time (57,58).…”

Molecular Imaging of Fluorinated Probes for Tau Protein and Amyloid-β Detection

“…To eliminate this issue, increasing the amount of magnetically equivalent fluorine atoms per molecule is needed. This can be done either through attaching additional CF3 groups to the probe or through conjugating the probe to perfluorinated macromolecules, which are currently used to track the cell activity in vivo using MRI [ 110 , 111 ]. A higher affinity of fluorescence probes allows the reduction of the background signal due to nonspecific binding and, therefore, tends to increase the signal-to noise-ratio (SNR).…”

Hot spot 19F magnetic resonance imaging of inflammation

“…The principle feasibility for in vivo imaging of the mixed labeled cell population was demonstrated after ex vivo labeling and subcutaneous injection. More recently, Chirizzi et al (2019) utilized PFCE and PERFECTA to track mononuclear cells in mice by multicolor 19 F MRI (Chirizzi et al, 2019). However, due to the large chemical shift differences of the individual 19 F peaks, the PFC multicolor approach is not restricted to two items: The group of Akazawa et al already used three different types of PFC-encapsulated silica nanocarriers with distinct 19 F MR chemical shifts and showed the usefulness for multicolor in vivo imaging by injecting them subcutaneously ( Figure 5, (Akazawa et al, 2018).…”