Towards Quantification of Inflammation in Atherosclerotic Plaque in the Clinic – Characterization and Optimization of Fluorine-19 MRI in Mice at 3 T

Abstract

Fluorine-19 (19F) magnetic resonance imaging (MRI) of injected perfluorocarbons (PFCs) can be used for the quantification and monitoring of inflammation in diseases such as atherosclerosis. To advance the translation of this technique to the clinical setting, we aimed to 1) demonstrate the feasibility of quantitative 19F MRI in small inflammation foci on a clinical scanner, and 2) to characterize the PFC-incorporating leukocyte populations and plaques. To this end, thirteen atherosclerotic apolipoprotein-E-knockout mice received 2 × 200 µL PFC, and were scanned on a 3 T clinical MR system. 19F MR signal was detected in the aortic arch and its branches in all mice, with a signal-to-noise ratio of 11.1 (interquartile range IQR = 9.5–13.1) and a PFC concentration of 1.15 mM (IQR = 0.79–1.28). Imaging flow cytometry was used on another ten animals and indicated that PFC-labeled leukocytes in the aortic arch and it branches were mainly dendritic cells, macrophages and neutrophils (ratio 9:1:1). Finally, immunohistochemistry analysis confirmed the presence of those cells in the plaques. We thus successfully used 19F MRI for the noninvasive quantification of PFC in atherosclerotic plaque in mice on a clinical scanner, demonstrating the feasibility of detecting very small inflammation foci at 3 T, and advancing the translation of 19F MRI to the human setting.

Multispectral fluorine-19 MRI enables longitudinal and noninvasive monitoring of tumor-associated macrophages

“…To date, the application of PFCs to image immune cells in cancer has largely relied on the ex vivo labeling of specific cell types in the context of monitoring cell-based therapies, such as adoptive T cell transfer and dendritic cell-based cancer vaccination (56,57). In vivo, only a handful of studies have explored the distribution of injected PFC-NP to image myeloid cells (25,34,37,(58)(59)(60), and the subcellular composition of the labeled myeloid cells has been minimally investigated (61). Moreover, the extent of brain microenvironmental heterogeneity has been underscored by recent singlecell analyses, with potential translational implications (62).…”

Nanotechnology as a Versatile Tool for 19F-MRI Agent’s Formulation: A Glimpse into the Use of Perfluorinated and Fluorinated Compounds in Nanoparticles

“…A plethora of studies are underway to evaluate the various properties of PFCs. They are found feasible for applications such as hypothermic total or partial liquid ventilation of the lungs [135][136][137][138][139], in vivo visualization of the effects of antibiotic therapy [140], oligonucleotide therapeutics [141], cell tracking [142], including stem cells [143][144][145], specific detection of organ rejection [146], identifying penumbra in stroke patient [147], quantifying immune cells (tumour-associated macrophages) in the tumour microenvironment [148][149][150], organ preservation [151], quantifying renal vascular damage [152], 19 F-oximetry [153], inflammation imaging of various diseases [154][155][156][157][158][159], gasification-enhanced photoacoustic cavitation [160] etc. There are some excellently written reviews for further reference on PFCs used for oxygen delivery [55,63,73,124,[161][162][163][164], imaging inflammation [48,91,165,166], and cell tracking [65,98,…”

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

“…23 For in vivo cell labeling, intravenously injected NE undergoes an opsonization process at the NE droplet surface that promotes endocytosis by phagocytic immune cells, predominantly monocytes and macrophages, providing a streamlined approach for imaging regions of inflammation. 24 Intravenously injected FC NE has been shown to be effective in the diagnosis of atherosclerosis, 25 arthritis, 26 neuroinflammation, 27 and tumors 28 using 19 F MRI.…”