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Purpose: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging., Procedures: Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths., Results: PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light., Conclusions: CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Purpose: We explore the use of intravenously delivered perfluorocarbon (PFC) nanoemulsion and 19 F MRI for detecting inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD). Correlative studies of 1 H-based liver proton density fat fraction (PDFF) and T 1 measurements and histology are also evaluated., Procedures: C57BL/6 mice were fed standard or high-fat diet (HFD) for 6 weeks to induce NAFLD. 1 H MRI measurements of PDFF and T 1 relaxation time were performed at baseline to assess NAFLD onset prior to administration of a PFC nanoemulsion to enable 19 F MRI of liver PFC uptake. 1 H and 19 F MRI biomarkers were acquired at 2, 21, and 42 days post-PFC to assess changes. Histopathology of liver tissue was performed at experimental endpoint., Results: Significant increases in liver volume, PDFF, and total PFC uptake were noted in HFD mice compared to Std diet mice. Liver fluorine density and T 1 relaxation time were significantly reduced in HFD mice., Conclusions: We demonstrated longitudinal quantification of multiple MRI biomarkers of disease in NAFLD mice. The changes in liver PFC uptake in HFD mice were compared with healthy mice that suggests that 19 F MRI may be a viable biomarker of liver pathology., (© 2022. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Purpose: We aim to develop perfluorocarbon-based nanoemulsions with improved sensitivity for detection of inflammatory macrophages in situ using F-19 MRI. Towards this goal, we evaluate the feasibility of nanoemulsion formulation incorporating a metal chelate in the fluorous phase which shortens the F-19 longitudinal relaxation rate and image acquisition time., Procedures: Perfluorinated linear polymers were conjugated to metal-binding tris-diketonate, blended with unconjugated polymers, and emulsified in water. Phospholipid-based surfactant was used to stabilize nanoemulsion and provide biocompatibility. Nanoemulsions were metalated with the addition of ferric salt to the buffer. Physical stability of surfactant and nanoemulsion was evaluated by mass spectrometry and dynamic light scattering measurements. Nanoemulsions were injected intravenously into a murine granuloma inflammation model, and in vivo 19 F/ 1 H MRI at 11.7 T was performed., Results: We demonstrated stability and biocompatibility of lipid-based paramagnetic nanoemulsions. We investigated potential oxidation of lipid in the presence of metal chelate. As a proof of concept, we performed non-invasive monitoring of macrophage burden in a murine inflammation model following intravenous injection of nanoemulsion using in vivo F-19 MRI., Conclusion: Lipid-based nanoemulsion probes of perfluorocarbon synthesized with iron-binding fluorinated β-diketones can be formulated for intravenous delivery and inflammation detection in vivo.