Imaging neuroinflammatory processes with USPIO-MRI

This thesis examines the utility of USPIO-MRI to provide a tool of tracking macrophage recruitment to sites of neuroinflammation within the CNS. Recruited macrophages and microglia resident in CNS tissue play a key role in the pathophysiology of a number of neuroinflammatory diseases such as neuropathic pain and multiple sclerosis. Under activated conditions, microglia and macrophages will phagocytose invading cells and CNS debris. It has been shown that ultrasmall superparamagnetic particles of iron oxide (USPIO), such as Sinerem, injected systemically, are engulfed by macrophages, which in turn migrate to sites of tissue injury. USPIOs can be visualised as a distinct reduction in signal intensity on T2* weighted MR images. However, there are still some issues regarding the distinction between iron-laden recruited macrophages and the entry of free iron across a permeable blood brain barrier (BBB) in disease cases. Hence, it was shown that intravenously injected Sinerem is cleared from the peripheral circulation within 24 hours, indentifying this as a time point as suitable for MCP-1 injection. Data showed that free USPIO can be visualised in the brain and that there is a linear relationship between Sinerem concentration and T2* signal intensity changes. MCP-1 induces macrophage recruitment to the site of microinjection and causes BBB breakdown at between 3 and 4 hours. In particular it was shown that T2* signal intensity changes are seen, in the presence of an intact BBB, as a result of Sinerem laden macrophages. This finding was verified by the co-localisation of ED-1 positive cells and Prussian blue positive regions. It was demonstrated that there is a strong correlation between T2* signal changes and the number of macrophages. This demonstrates that USPIO-MRI can be used to characterise macrophage infiltration in neuroinflammation in the presence of an intact BBB.This thesis is not currently available in OR