In vivo MRI of brain inflammation in human ischaemic stroke

• Published in: Brain (London, England : 1878) Vol. 127; no. 7; pp. 1670 - 1677
• Main Authors: Saleh, Andreas, Schroeter, Michael, Jonkmanns, Cornelia, Hartung, Hans‐Peter, Mödder, Ulrich, Jander, Sebastian
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2004; Oxford Publishing Limited (England)
• Subjects: Aged; Biological and medical sciences; Brain - immunology; Brain Ischemia - immunology; Contrast Media; DWI = diffusion‐weighted imaging; Female; Ferric Compounds; FLAIR = fluid‐attenuated inversion recovery; FLASH = fast low angle shot; FOV = field of view; Gadolinium; Humans; Image Processing, Computer-Assisted; Inflammation; macrophages; Macrophages - pathology; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Neurology; PWI = perfusion‐weighted imaging; ROI = region of interest; SI = signal intensity; stroke; TE = echo time; TGSE = turbo gradient spin‐echo; TR = repetition time; USPIO = ultrasmall superparamagnetic iron oxide; magnetic resonance imaging; Iron oxide; Central nervous system; Cardiovascular disease; Gadolinium; Blood brain barrier; Contrast effect; Transients; Vascular disease; macrophages; Ischemia; Phase II trial; Breakdown; Cerebrovascular disease; Contrast media; Human; Clinical test; Stroke; Nervous system diseases; Weight loss; Inflammation; Nuclear magnetic resonance imaging; Cerebral disorder; Anatomic pathology; Cell population; Central nervous system disease; Medical imagery; Infiltration; Inflammatory cell; In series; Macrophage
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awh191

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.