Blood oxygenation level dependent effect of cerebral ischemic penumbra in monkey reversible middle cerebral artery occlusion model

Abstract

Objective To investigate the value of blood oxygenation level dependent (BOLD) MRI in detecting monkey cerebral ischemic penumbra (IP). Methods Six monkeys were used to make reversible middle cerebral artery occlusion (MCAO) model by an interventional microcatheter method. MR DWI, PWI mean transit time (MTT), T_2WI and quantitative T_2 map, T_2~* map were performed at MCAO (0 h) and 1,3,6,12,24,48 h after reperfusion. Reversible transverse relaxation rate (R_2') BOLD imaging was calculated using quantitative T_2 and T_2~* maps. Lesion volume percentage (lesion volume/bilateral hemispheres volume) were measured on 0 h DWI,48 h T_2WI and TTC staining. Ischemic area was subdivided into infracted core (high signal area on both 0 h DWI and 48 h T_2 WI), IP (high signal on 0 h DWI, iso on 48 h T_2 WI) and oligemia (0 h delayed MTT, iso signal on both 0 h DWI and 48 h T_2 WI). Relative R_2' (rR_2') was calculated to get ratio between the lesion and mirror area in contralateral healthyhemisphere. Paired t test and correlation analysis were used for comparison of lesion volume percentage. rR_2' values at each time point were compared by ANOVA. Results Reversible MCAO models were made successfully in 4 of 6 monkeys. Lesion volume porcentage on 48 h T_2 WI was reduced compared to that on Oh DWI [ (8.16±0.55)% vs (11.37±1.41)% ,t=6.472,P 0.05], which showed significant positive correlation (r=0.98, P<0.05). rR_2' values were significant different at each time point, with highest in ohgemia followed by IP and infarcted core (P< 0.05). rR_2' values in infracted core, IP and oligemia were: 0 h(1.129±0.108,1.329±0.081,1.584± 0.103,F=36.19,P<0.05),1 h(0.668±0.082,1.237±0.072,1.435±0.066,F=134.09,P<0.05), 3 h (0.536±0.075,1.453±0.081,1.770±0.141, F=256.30, P<0.05), 6 h (0.259±0.050,2.435± 0.131,2.957±0.177,F=803.25,P<0.05), 12 h(0.385±0.054,2.447±0.148,3.254±0.184,F= 743.74,P<0.05),24 h(0.083±0.026,1.968±0.127,3.101±0.144,F=1236.26,P<0.05),48 h (0.246±0.058,3.694±0.218,4.297±0.322, F=557.02, P<0.05). After reperfusion, rR_2' values in IP and oligemia showed increased trend with time evolution and reflected positive BOLD effect, while the infracted core showed decreased trend, reflecting negative BOLD effect. Conclusion R_2' BOLD can delineate IP from infracted core according to the difference of oxygen metabolic status in ischemic brain tissue. Key words: Infarction,middle cerebral artery; Magnetic resonance imaging; Animal experimentation