Superparamagnetic iron oxide nanocolloids in MRI studies of neuroinflammation

Iron oxide (IO) nanocolloids are being increasingly used to image cellular contribution to neuroinflammation using MRI, as these particles are capable of labeling circulating cells with phagocytic activity, allowing to assess cell trafficking from the blood to neuroinflammation sites. The use of IOs relies on the natural phagocytic properties of immune cells, allowing their labeling either in vitro or directly in vivo, following intravenous injection. Despite concerns on the specificity of the latter approach, the widespread availability and relatively low cost of these techniques, coupled to a sensitivity that allows to reach single cell detection, have promoted their use in several preclinical and clinical studies. In this review, we discuss the results of currently available preclinical and clinical IO-enhanced MRI studies of immune cell trafficking in neuroinflammation, examining the specificity of the existing findings, in view of the different possible mechanisms underlying IO accumulation in the brain. From this standpoint, we assess the implications of the temporal and spatial differences in the enhancement pattern of IOs, compared to gadolinium-based contrast agents, a clinically established MRI marker blood-brain barrier breakdown. While concerns on the specificity of cell labeling obtained using the in-vivo labeling approach still need to be fully addressed, these techniques have indeed proved able to provide additional information on neuroinflammatory phenomena, as compared to conventional Gadolinium-enhanced MRI.