title: In vivo MRI of brain inflammation in human ischaemic stroke.
abstract: Inflammation contributes to brain damage caused by ischaemic stroke. Macrophages, as the prevailing inflammatory cell population in stroke lesions, can be visualized using ultrasmall superparamagnetic iron oxide (USPIO) as a cell-specific 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 first 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. Vessel-associated changes appeared as signal loss on T2/T2*-weighted images and decreased from the first to second scan after USPIO infusion, most likely reflecting a transient blood pool effect of the contrast agent. Conversely, parenchymal enhancement was mainly evident on T1-weighted 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 infiltration by USPIO-laden macrophages. Thus, USPIO-enhanced MRI may provide an in vivo surrogate marker of cellular inflammation in stroke and other CNS pathologies.
authors.affiliation: Instritute of Diagnostic, University Hospital, Heinrich-Heine-University, Dusseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Saleh
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.forename: Cornelia
authors.initials: C
authors.lastname: Jonkmanns
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mödder
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jander
mesh_terms: D000368:Aged; D001921:Brain / Q000276:immunology*; D002545:Brain Ischemia / Q000276:immunology*; D003287:Contrast Media; D005260:Female; D005290:Ferric Compounds; D005682:Gadolinium; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007249:Inflammation; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide; D005682:Gadolinium