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Brain Advance Access published online on May 5, 2004
Brain, doi:10.1093/brain/awh191
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Received December 23, 2003
Revised March 10, 2004
Accepted March 14, 2004

Article

In vivo MRI of brain inflammation in human ischaemic stroke

Andreas Saleh 1, Michael Schroeter 2, Cornelia Jonkmanns 1, Hans-Peter Hartung 2, Ulrich Mödder 1, Sebastian Jander 2*

1 Institute of Diagnostic Radiology, University Hospital, Düsseldorf, Germany
2 Department of Neurology, University Hospital, Düsseldorf, Germany

* To whom correspondence should be addressed. E-mail: jander{at}uni-duesseldorf.de.


  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.

Key Words: stroke; inflammation; magnetic resonance imaging; contrast media; macrophages


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