猴可复性大脑中动脉闭塞模型脑缺血半暗带的血氧水平依赖效应

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

目的 探讨血氧水平依赖（BOLD）MRI对确定猴脑缺血半暗带（IP）的价值。方法成年恒河猴6只，应用微导管法制作猴可复性大脑中动脉闭塞（NCAO）模型。MCAO后0h、再灌注后1、3、6、12、24及48h分别进行DWI、PWI、T2WI、定量T2和T2＊扫描，根据T2和T2＊图计算可逆性横向弛豫率（R2’），用来表示BOLD效应（R2’BOLD）。计算动脉闭塞期DWI（0hDWI）、再灌注48hT2WI（48hT2WI）及脑组织大体切片2，3，5-氯化三苯基四氮唑（TC）染色病灶体积百分比（病灶体积/双侧大脑半球体积）。将缺血组织划分为3个区域：梗死核心（0hDWI、48hT2WI均为高信号区）、IP（0hDWI高信号，48hT2WI等信号区）及低灌注区（0h平均通过时间延长但0hDWI、48hT2WI均为等信号区），分别测量3个区域R2’的相对值（患侧／健侧半球镜影区比值，rR2’）。病灶体积比比较采用配对t检验和相关分析，3个区域rR2’比较采用单因素方差分析。结果6只猴中4只造模成功。48hT2WI病灶体积比（8．16±0．55）％较0hDWI的（11．37±1．41）％明显缩小（t=6．472，P〈0．05）；TTC染色病灶体积比（8．15±0．62）％与48hT2WI的（8．16±0．55）％差异无统计学意义（t=0．150，P〉0．05），两者呈明显正相关（r=0．98，P〈0．05）。梗死核心、IP、低灌注区rR2’在各时间点差异均有统计学意义，梗死核心低于IP，IP低于低灌注区（P〈0．05），三者rR2’值：0h时分别为1．129±0．108、1．329±0．081、1．584±0．103（F=36．19，P〈0．05）。1h分别为0．668±0．082、1．237±0．072、1．435±0．066（F=134．09，P〈0．05）。3h分别为0．536±0．075、1．453±0．081、1．770±0．141（F=256．30，P〈0．05）。6h分别为0．259±0．050、2．435±0．131、2．957±0．177（F=803．25，P〈0．05）。12h分别为0．385±0．054、2．447±0．148、3．254±0．184（F=743．74，P〈0．05）。24h分别为0．083±0．026、1．968±0．127、3．101±0．144（F=1236．26，P〈0．05）。48h分别为0．246±0．058、3．694±0．218、4．297±0．322（F=557．02，P〈0．05）。随再灌注时间延长，IP和低灌注区的rR2’呈逐渐升高趋势，表现为负性BOLD效应；梗死核心呈逐渐降低趋势，表现为正性BOLD效应。结论R2’BOLD可以根据缺血脑组织氧代谢状态的不同来区分IP和梗死核心。

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）, T2WI and quantitative T2 map, T2＊ map were performed at MCAO （0h） and 1,3,6,12,24,48 h after reperfusion. Reversible transverse relaxation rate （ R2＇） BOLD imaging was calculated using quantitative T2 and T2 ＊ maps. Lesion volume percentage （lesion volume/bilateral hemispheres volume） were measured on 0 hDWI,48 h T2WI and TFC staining. Ischemic area was subdivided into infracted core （high signal area on both 0 h DWI and 48 h T2WI） , IP （high signal on 0 h DWI , iso on 48 h T2WI） and oligemia （0 h delayed MTT, iso signal on both 0 h DWI and 48 h T2WI）. Relative R2＇ （rR2＇） was calculated to get ratio between the lesion and mirror area in contralateral healthy hemisphere. Paired t test and correlation analysis were used for comparison of lesion volume percentage. rR2＇ values at each time point were compared by ANOVA. Results Reversible MCAO models were made successfully in 4 of 6 monkeys. Lesion volume percentage on 48 h T2WI was reduced compared to that on Oh DWI [ （8. 16±0. 55 ） % vs （ 11.37 ± 1.41 ） %, t = 6. 472, P 〈 0.05 ]. There was no significant difference in lesion volume percentage between TFC staining and 48 h T2 WI [ （ 8.15 ±0. 62） % vs （ 8.16 ± 0. 55 ） % , t = 0. 150,P 〉 0.05 ], which showed significant positive correlation （ r = 0. 98, P 〈 0.05 ）. rR2＇ values were significant different at each time point, with highest in oligemia followed by IP and infarcted core （P 〈 0. 05 ）. rR2＇ values in infracted core, IP and oligemia were ： 0 h （ 1. 129 ± 0. 108,1. 329 s 0. 081,1. 584 s 0. 103 ,F =36. 19,P 〈0. 05） ,1 h（0. 668 s0. 082,1. 237 ±0. 072,1. 435 ±0. 066,F = 134. 09,P 〈0. 05）, 3 h （0. 536 s 0. 075,1. 453 ± 0.081,1. 770 ± 0. 141, F = 256. 30, P 〈 0.05 ）, 6 h （ 0. 259 s 0. 050,2. 435 ± 0. 131,2.957 s0. 177,F = 803.25,P 〈0.05） ,12 h（0. 385 ±0.054,2.447 s0. 148,3.254 s0. 184,F = 743.74, P 〈 0. 05） ,24 h （ 0. 083± 0. 026,1. 968 ± 0. 127,3. 101 s 0. 144, F = 1236. 26, P 〈 0. 05 ）, 48 h （0. 246 s 0. 058,3. 694 s 0. 218,4. 297 s 0. 322, F = 557.02, P 〈 0. 05 ）. After reperfusion, rR2＇ 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 R2＇ BOLD can delineate IP from infracted core according to the difference of oxygen metabolic status in ischemic brain tissue.