title: Post-ischemic leakiness of the blood-brain barrier: a quantitative and systematic assessment by Patlak plots.
abstract: The Patlak plot analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows estimation of blood-brain barrier (BBB) leakage following temporary focal cerebral ischemia. Thus far, a systematic and quantitative in vivo evaluation of post-ischemic BBB leakage is lacking. Here, using DCE-MRI and the Patlak plot method, we quantitatively assessed BBB leakage in rats at the following time-points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. Sham-operated animals served as controls. Data collected for each time-point were: the blood-to-brain transfer rate constant (K(i)) of the contrast agent gadolinium, distribution volume (V(p)), ischemic lesion volume, and apparent diffusion coefficient (ADC) values. Compared to controls, K(i), measured at all time-points, except for 5 weeks, appeared significantly different (p<0.001). At several time-points (25 min, 48 and 72 h, 4 and 5 weeks), V(p) was similar compared to that of controls, but for the remaining groups the difference was significant (p<0.001). Analyzing the relationship of K(i) values to time-points, we observed a trend towards a decrease over time (r=-0.61, p=0.014). Both ADC values (r=-0.58, p=0.02) and ischemic lesion volumes (r=0.75, p=0.0015) correlated with K(i) values. These results suggest that after ischemia-reperfusion in rats, BBB leakage is continuous during a 4-week period. Its magnitude diminishes over time and correlates with severity and extent of ischemic injury.
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland.
authors.forename: Usama
authors.initials: U
authors.lastname: Abo-Ramadan
authors.forename: Aysan
authors.initials: A
authors.lastname: Durukan
authors.forename: Miia
authors.initials: M
authors.lastname: Pitkonen
authors.forename: Ivan
authors.initials: I
authors.lastname: Marinkovic
authors.forename: Ertugrul
authors.initials: E
authors.lastname: Tatlisumak
authors.forename: Eric
authors.initials: E
authors.lastname: Pedrono
authors.forename: Lauri
authors.initials: L
authors.lastname: Soinne
authors.forename: Daniel
authors.initials: D
authors.lastname: Strbian
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology*; D001929:Brain Edema / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003287:Contrast Media; D018450:Disease Progression; D005682:Gadolinium; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D003287:Contrast Media; D005682:Gadolinium