In Vivo Imaging of Stepwise Vessel Occlusion in Cerebral Photothrombosis of Mice by 19F MRI

Abstract

Background 19F magnetic resonance imaging (MRI) was recently introduced as a promising technique for in vivo cell tracking. In the present study we compared 19F MRI with iron-enhanced MRI in mice with photothrombosis (PT) at 7 Tesla. PT represents a model of focal cerebral ischemia exhibiting acute vessel occlusion and delayed neuroinflammation.Methods/Principal FindingsPerfluorocarbons (PFC) or superparamagnetic iron oxide particles (SPIO) were injected intravenously at different time points after photothrombotic infarction. While administration of PFC directly after PT induction led to a strong 19F signal throughout the entire lesion, two hours delayed application resulted in a rim-like 19F signal at the outer edge of the lesion. These findings closely resembled the distribution of signal loss on T2-weighted MRI seen after SPIO injection reflecting intravascular accumulation of iron particles trapped in vessel thrombi as confirmed histologically. By sequential administration of two chemically shifted PFC compounds 0 and 2 hours after illumination the different spatial distribution of the 19F markers (infarct core/rim) could be visualized in the same animal. When PFC were applied at day 6 the fluorine marker was only detected after long acquisition times ex vivo. SPIO-enhanced MRI showed slight signal loss in vivo which was much more prominent ex vivo indicative for neuroinflammation at this late lesion stage.ConclusionOur study shows that vessel occlusion can be followed in vivo by 19F and SPIO-enhanced high-field MRI while in vivo imaging of neuroinflammation remains challenging. The timing of contrast agent application was the major determinant of the underlying processes depicted by both imaging techniques. Importantly, sequential application of different PFC compounds allowed depiction of ongoing vessel occlusion from the core to the margin of the ischemic lesions in a single MRI measurement.

Noninvasive Imaging of Early Venous Thrombosis by 19 F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions

“…Until now, 19 F MRI has been used predominantly for immune cell tracking in a variety of clinically relevant inflammation models. [21][22][23][24][25][26][27][28][29] This approach is based on the rapid uptake of intravenously injected PFCs by circulating monocytes that subsequently migrate into the inflamed area, resulting in a local accumulation of 19 F-loaded immune cells. In the present study, we report a novel procedure for the generation of targeted PFCs that makes use of a sterol-based postinsertion technique (SPIT) to generate α2-antiplasminlabeled PFCs (α2 AP -PFCs).…”

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

“…[32][33][34][35][36] However, these studies used a chemical shift imaging (CSI) approach with bSSFP to allow for visualization of the different spatial distributions of chemically shifted PFC compounds. Overall, the vast majority of studies that perform cell tracking with 19 F MRI have employed spin echo sequences.…”

Neuroinflammatory Imaging Biomarkers: Relevance to Multiple Sclerosis and its Therapy

“…In combination with anatomical 1 H-MRI, "hot spot" 19 F images can be superimposed on 1 H images generated in the same imaging session [65]. The technique was applied to monitor neuroinflammation in a focal model of nerve inflammation [66] and in neuroinflammation associated with ischemia in photothrombosis model [64,67]. However, no data are yet available in an MS model, probably because of sensitivity constraints related to low concentration of cells.…”