In vivo imaging of inflammation in the peripheral nervous system by 19F MRI

Visualization of neuroinflammation is still a major task in neuroscience and neurology since inflammatory processes play a central pathophysiological role in many disorders of the nervous system but are not yet covered by conventional imaging techniques.Recently, 19F magnetic resonance imaging (MRI) was introduced as a new cellular imaging technology. In the present study, we established 19F high field MRI for cell tracking in the peripheral nervous system (PNS) of rats using dedicated MR coils. To mimic focal neuroinflammation, lysolecithin was locally injected into the left sciatic nerve inducing demyelination followed by severe infiltration of monocytes/macrophages from the circulation. Systemic administration of perfluorocarbons (PFC) led to a fluorine signal along the proximal stretch of the affected sciatic nerves in in vivo19F MRI which was not seen on the right healthy side. The preferential in vivo uptake of PFC by circulating mononuclear cells was confirmed by density gradient centrifugation of the blood. Removal of nerves with consecutive ex vivo19F MRI and additional 19F spectroscopy for quantification corroborated the localization of the 19F marker within the injured nerves (1.07 × 1018 ± 1.00 × 1018 mean detectable fluorine spins) while contralateral naive nerves did not exhibit any detectable fluorine signal. Histological assessment confirmed the presence of numerous ED1-positive macrophages within the nerve lesions. Control experiments showed that intraneural application of saline led to an inflammatory reaction restricted to the perineurium which could also be detected by 19F MRI. In conclusion, we show that 19F MRI is a promising new technology to visualize hematogenous macrophage responses in the nervous system.

Research highlights
► 19F MRI allows in vivo visualization of inflammation in the peripheral nervous system.
► Inflammation is detected unambiguously with high spatial resolution.
► Quantification of the fluorine signal is possible with ex vivo19F spectroscopy.