The dogma of central nervous system (CNS) immune-privilege began to break down with the realization that immune cell infiltration into the CNS may be more common than previously believed. In addition to neurological disease, there is now growing evidence that neural-immune crosstalk may even occur in non-disease conditions of the healthy brain. However, little is known about the kinetics of immune cells in healthy and diseased CNS, because it is difficult to perform long-term visualization of cell motility in the live tissue with minimal invasion. Non-invasive monitoring of immune cells in the CNS may lead to a greater understanding of the mechanisms of the immune systems in CNS homeostasis and progression of diseases. Here, we report the possibility of highly sensitive in-vivo MRI techniques monitoring the cell migration in the CNS at the single-cell level.
MRI was conducted on an 11.7 T system for small animal. Superparamagnetic particles of iron oxide (SPIO; 60 nm in diameter) were injected into the tail veins in each subject and T2*-weighted images were taken sequentially. The distribution of the SPIO-induced signal void in the mouse brain was checked in normal and several disease-model animals.
We demonstrate that MRI with intravenous administration of SPIO can be used to successfully monitor the transmigration of peripheral phagocytes into healthy and diseased brains, as intracellular absorbed-SPIO can pass through the blood-brain barrier (BBB). We confirmed that macrophages and monocytes were the main transporters of SPIO to the brain. In addition, we extend the use of MRI as a tool to monitor dynamic behaviors of immune cell migration in the brain with time-lapse MRI movie. Time-lapse MRI can track dynamic single-cell migration in the whole mouse brain non-invasively.
Our high resolution in-vivo MRI technique may reveal critical insights into cell behaviors that are not obtained by optical microscopy. Our technique could contribute to understand the neuro-immune crosstalk and to reveal the mechanisms of immune cell dynamics in the normal CNS as well as neuroimmunological diseases.