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.

Imaging in sepsis-associated encephalopathy—insights and opportunities

“…58 The same agent has been used in a model of ischaemic stroke to demonstrate widespread transient increases in BBB breakdown. 59 Another study showed changes in the circumventricular organs during EAE, which the authors correlated with disease severity and onset. 60 Another study found no changes in Gf enhancement after intraperitoneal injection of LPS.…”

Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

“…Consistent with previous studies, macroscopic sections confirmed BBB breakdown in most layers of the cortex surrounding the lesion core ( Figure 1A, bottom). 8,28,29 Cellular damage was detected in the peri-ischemic region using intravital microscopy after intravenous injection of either PI or binding annexin A5, while nonbinding annexin A5 gave no specific staining ( Figure 1B). Positive annexin A5 staining, while generally colocalized with PI (n = 4), was most prominent in close proximity to blood vessels, mainly venules.…”

Immunomodulatory medicines for multiple sclerosis: Progress and prospects

“…Such leukocyte trafficking is probably a key event in the pathophysiology of MS [Bahbouhi et al, 2009;Kerfoot and Kubes, 2002] that contributes to the localized breakdown of the BCNSB. Both gadolinium diethylenetriaminepenta-acetate (Gd-DTPA)-and iron oxideenhanced MRI has indicated BCNSB breakdown in MS as well as in an experimental model of MS: EAE [Stoll et al, 2009] and postmortem MRI indicate alterations in both focal and diffuse BCNSB abnormalities in subjects with MS [Vos et al, 2005]. There is also evidence to indicate that dynamic contrastenhanced MRI is able to detect subtle blood-brain barrier leakage in visibly non-enhancing MRI lesions in MS [Soon et al, 2007].…”