title: Transient widespread blood-brain barrier alterations after cerebral photothrombosis as revealed by gadofluorine M-enhanced magnetic resonance imaging.
abstract: Magnetic resonance imaging (MRI) is a powerful tool to assess brain lesions, but currently available contrast agents are limited in the assessment of cellular and functional alterations. By use of the novel MRI contrast agent gadofluorine M (Gf) we report on imaging of transient and widespread changes of blood-brain barrier (BBB) properties as a consequence of focal photothrombotic brain lesions in rats. After i.v. application, Gf led to bright contrast in the lesions, but also the entire ipsilateral cortex on T1-weighted MRI. In contrast, enhancement after application of gadolinium diethylenetriamine-pentaacetic acid (Gd-DTPA), a common clinical indicator of BBB leakage was restricted to the lesions. Remote Gf enhancement was restricted in time to the first 24 h after photothrombosis and corresponded to a transient breakdown of the BBB as revealed by extravasation of the dye Evans blue. In conclusion, our study shows that Gf can visualize subtle disturbances of the BBB in three dimensions not detectable by Gd-DTPA. Upon entry into the central nervous system Gf most likely is locally trapped by interactions with extracellular matrix proteins. The unique properties of Gf hold promise as a more sensitive contrast agent for monitoring BBB disturbances in neurologic disorders, which appear more widespread than anticipated previously.
authors.affiliation: Department of Neurology, University of Wuerzburg, Wuerzburg, Germany. stoll_g@klinik.uni-wuerzburg.de
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Stefan
authors.initials: S
authors.lastname: Braeuninger
authors.forename: Chi Wang
authors.initials: CW
authors.lastname: Ip
authors.forename: Carsten
authors.initials: C
authors.lastname: Wessig
authors.forename: Ingo
authors.initials: I
authors.lastname: Nölte
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D003287:Contrast Media / Q000378:metabolism; D005466:Fluorocarbons; D019786:Gadolinium DTPA / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; D016194:Receptors, N-Methyl-D-Aspartate; C517961:gadofluorine M; D019786:Gadolinium DTPA