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Inflammatory and resolution stages of hepatic injury: imaging with USPIO-enhanced MRI in mice
Joao Piraquive Agudelo1, Sabrina Doblas1, Katell Peoc'h2
1Laboratory of Imaging Biomarkers, Center for Research on Inflammation, Inserm U1149, Université Paris Cité, Paris, France.
Objective:
Liver injury includes inflammation and resolution stages with different macrophage populations. Hepatic macrophages can be imaged with ultrasmall paramagnetic iron oxide (USPIO) nanoparticles-enhanced magnetic resonance imaging (MRI). We aimed to assess if inflammation and resolution stages of liver injury could be differentiated with USPIO-enhanced MRI in mice.
Materials And Methods:
Three groups of C57BL/6JRj mice (control, inflammation, resolution; n = 10 for each group) were imaged. Liver fibrosis was induced by intraperitoneal carbon tetrachloride injections for 6 weeks. Multigradient-echo MRI was performed before, 24, and 48 h after intravenous injection of fluorescent USPIO. Contrast uptake was quantified with measurements. Macrophages were immunostained with F4/80, and USPIO fluorescence was localized and quantified with confocal microscopy. Liver iron content was measured with inductively coupled mass spectrometry (ICP-MS). was assessed with Mann-Whitney tests. Kruskal-Wallis and Dunn tests compared fibrosis, fluorescence, and ICP-MS iron concentration. Spearman tests were used for correlation analysis.
Results:
was significantly higher in the inflammation group (158 ± 85%) compared to the control (58 ± 36%, p = 0.020) and resolution (71 ± 36%, p = 0.048) groups. Confocal microscopy showed a high macrophage number and USPIO uptake in the inflammation group. correlated with macrophages number (r = 0.67, p = 0.0001), USPIO fluorescence intensity (r = 0.58, p = 0.0011), and iron concentration at ICP-MS (r = 0.39, p = 0.028).
Conclusion:
Our results suggest that the inflammatory and resolution stages of hepatic injury can be assessed with USPIO-enhanced MRI.
Relevance Statement:
Our study demonstrates that USPIO-enhanced MRI can be used to monitor the inflammatory and resolution phases of hepatic injury in mice. If future studies confirm these findings, this imaging method might be valuable for tracking hepatic inflammation dynamics.
Key Points:
Liver was highest during the inflammatory stage and partially reversed during the resolution stage, reflecting macrophage dynamics. Immunofluorescence showed increased macrophage number and uptake during inflammation, decreasing during resolution. Iron concentration significantly correlated with , macrophage number, and total fluorescence intensity.
Insights
Ultrasmall paramagnetic iron oxide (USPIO) enhanced MRI can differentiate liver injury stages in mice. This imaging technique tracks macrophage dynamics during inflammation and resolution, offering potential for monitoring liver disease progression.
Area of Science:
- Hepatology
- Medical Imaging
- Nanotechnology
Background:
- Liver injury involves distinct inflammatory and resolution phases characterized by dynamic macrophage populations.
- Hepatic macrophages are potential targets for imaging using ultrasmall paramagnetic iron oxide (USPIO) nanoparticles with magnetic resonance imaging (MRI).
Purpose of the Study:
- To evaluate the efficacy of USPIO-enhanced MRI in distinguishing between the inflammation and resolution stages of liver injury in a mouse model.
- To correlate MRI findings with macrophage activity and iron concentration in the liver.
Main Methods:
- Three groups of mice (control, inflammation, resolution) were subjected to carbon tetrachloride-induced liver fibrosis.
- Multigradient-echo MRI was performed before and after USPIO injection, with contrast uptake quantified by ΔR2* measurements.
- Macrophage presence and USPIO localization were assessed via F4/80 immunostaining and confocal microscopy, alongside liver iron content analysis using ICP-MS.
Main Results:
- Significantly higher ΔR2* values were observed in the inflammation group compared to control and resolution groups (p < 0.05).
- Confocal microscopy confirmed increased macrophage numbers and USPIO uptake during inflammation, which decreased during resolution.
- ΔR2* measurements showed significant correlations with macrophage count, USPIO fluorescence intensity, and liver iron concentration.
Conclusions:
- USPIO-enhanced MRI can effectively differentiate the inflammatory and resolution stages of hepatic injury in mice.
- This imaging modality shows promise for monitoring the dynamic changes of hepatic inflammation and macrophage activity.
