Early Assessment of Pulmonary Inflammation by ¹⁹ F MRI In Vivo

Abstract

Background Emulsified perfluorocarbons (PFCs) are preferentially phagocytized by monocytes/macrophages and are readily detected by 19F MRI. This study tests the hypothesis that 19F MRI can be used to quantitate pulmonary inflammation by tracking of infiltrating PFC-loaded monocytes. Methods and Results Pneumonia was induced in mice by intratracheal instillation of LPS followed by intravenous injection of PFCs. While regular 1H MRI provided no evidence of lung injury 24 hrs post-LPS, the concurrent 19F images clearly show PFC accumulation in both pulmonary lobes. Imaging at 48 hrs post-LPS revealed signal in 1H images at the same location as the 24 hr 19F signals. Thus, progressive pneumonia was first predicted by 19F MRI early after PFC administration. Without LPS, at no time were 19F signals observed within the lung. Histology and FACS combined with 19F MRI confirmed the presence of infiltrating PFC-loaded monocytes/macrophages after LPS challenge. Additional experiments with graded doses of LPS demonstrated that 19F signal intensity strongly correlated with both LPS dose and pathological markers of lung inflammation. In separate studies, dexamethasone and CGS21680 (adenosine 2A receptor agonist) were used to demonstrate the ability of 19F MRI to monitor anti-inflammatory therapies. Conclusions PFCs serve as a contrast agent for the prognostic and quantitative assessment of pulmonary inflammation by in vivo 19F MRI, which is characterized by a high degree of specificity due to the lack of any 19F background. Since PFCs are biochemically inert, this approach may also be suitable for human applications.

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

“…Overall, the vast majority of studies that perform cell tracking with 19 F MRI have employed spin echo sequences. [16][17][18][19][37][38][39][40] Using the 3D bSSFP sequence, we injected and detected 1.5×10 6 Cell Sense-labeled hMSC in vivo on day 0 using a spatial resolution of 2 mm 3 (2 µL). If we assume that on day 0 all of the injected cells are present and evenly distributed, then we detected 30,000 cells per voxel.…”

“…Examples of 19 F MR imaging performed to date include: monitoring inflammation (tumor models, rheumatoid arthritis, lung injuries, and after ischemia in the lung or brain), [16][17][18][19] detection of T cell and dendritic cell migration, 20,21 and tracking the fate of transplanted hematopoietic and neural stem cells.…”

Sepsis: Principles of Diagnosis

“…Experimental data demonstrating the possibilities of in vivo detection of the inflammation in the lungs have been obtained [15]. Pneumonia in mice was caused by intratrcheal exposition of lipopolysaccharide (LPS).…”

New Cardiovascular Applications of the Turbo Spin Echo Sequence in Magnetic Resonance Imaging

“…Since then, 19 F imaging has also been utilized for cell-tracking [39,40], tumor imaging [41], and especially in imaging of inflammation [42][43][44][45][46][47]. The C-F bond in perfluorocarbons is amongst the strongest chemical bonds known to man; consequently, PFCs are some of the most stable and inert molecules available for any application.…”

“…Despite several examples of successful 19 F in vivo imaging [39][40][41][42][43][44][45][46][47], the MR experiment is inherently limited by low signal sensitivity, and fluorine MRI is often hindered by low SNR due to the limited number of fluorine nuclei that can be delivered to an area of interest. In order to obtain reasonable voxel sizes during an in vivo imaging session, dozens or hundreds of averaging scans are often used, resulting in lengthy examination times.…”