In vivo MRI of brain in ̄ammation in human ischaemic stroke

In ̄ammation contributes to brain damage caused by ischaemic stroke. Macrophages, as the prevailing in ̄ammatory cell population in stroke lesions, can be visualized using ultrasmall superparamagnetic iron oxide (USPIO) as a cell-speci®c contrast agent for MRI. In this single-centre open-labelled clinical phase II study we tested the potential of USPIO-enhanced MRI for macrophage imaging in human ischaemic stroke lesions. In a series of 10 consecutive patients, USPIO contrast agent was infused at the end of the ®rst week after symptom onset. Two follow-up MRI scans were performed 24±36 h and 48±72 h after infusion. Two distinct components of USPIO-related signal changes were discernible, one associated with blood vessels and one representing parenchymal enhancement. Vesselassociated changes appeared as signal loss on T2/T2*weighted images and decreased from the ®rst to second scan after USPIO infusion, most likely re ̄ecting a transient blood pool effect of the contrast agent. Conversely, parenchymal enhancement was mainly evident on T1weighted images, increased over time, and matched with the expected distribution of macrophages. Importantly, USPIO-induced signal alterations throughout differed from signatures of conventional gadolinium-enhanced MRI, thus being independent from breakdown of the blood±brain barrier. We suggest that increasing USPIO-enhancement on T1-weighted images indicates brain in®ltration by USPIO-laden macrophages. Thus, USPIO-enhanced MRI may provide an in vivo surrogate marker of cellular in ̄ammation in stroke and other CNS pathologies.