Amide proton transfer imaging of neonatal piglet with hypoxic ischemic brain injury

Amide proton transfer imaging of neonatal piglet with hypoxic ischemic brain injury

Objective To investigate the amide proton transfer (APT) values in basal ganglia of neonatal piglet hypoxic-ischemic brain injury (HIBI) model using MR APT imaging. Methods Totally 35 healthy neonatal piglets were selected. There were 5 piglets underwent sham-operation in control group and 30 piglets used to established HIBI models in HIBI group. According to the time interval between APT imaging and the establishment of HIBI model, the piglets in HIBI group were divided into 0—<2 h， 2—<6 h， 6—<12 h， 12—<24 h， 24—<48 h and 48—<72 h subgroups. APT imaging was performed on all piglets. The APT value of basal ganglia between control group and all the subgroups in HIBI group were compared. Results After HIBI occurred, the APT values immediately decreased in 0—2 h， and then increased gradually. In 24 h after HIBI, the APT values were mainly returned to the level of control group, then continuously increased. The APT value in control group and 0—<2 h， 2—<6 h， 6—<12 h， 12—<24 h， 24—<48 h， 48—<72 h subgroups in HIBI group were 0.52±0.09, -0.35±0.08, -0.02±0.14, 0.28±0.04, 0.46±0.11, 0.80±0.11, 1.24±0.18, respectively. The APT values between control group and each subgroups in HIBI group had significant differences (allP<0.01) except for 12—<24 h subgroup (P=0.68). Conclusion The APT value decreased firstly and then increased after HIBI in neonatal piglet. APT imaging can provide a non-invasive molecular MR method to evaluate the pathophysiological changes of HIBI.

Brain injuries; Hypoxia-ischemia, brain; Piglet; Amide proton transfer

脑部活动所需能量大部分来自葡萄糖的有氧代谢[1]，正常代谢状态下，脑内葡萄糖及乳酸保持动态平衡，但当脑内缺氧缺血(hypoxia-ischemia, HI)时，有氧代谢障碍[2]，有氧代谢转为无氧代谢，脑组织内无氧代谢过程产生的乳酸增多，堆积的乳酸致使糖代谢受到抑制，加重细胞内酸中毒[3]。酰胺质子转移(amide proton transfer, APT)成像是一种分子水平MR成像新技术，其原理是利用特定频率的脉冲来饱和细胞内游离蛋白质和多肽上的酰胺质子，因饱和的酰胺质子与自由水质子间存在化学交换，进而产生水信号的变化[4]。理论上，APT信号强度主要取决于酰胺质子和水质子的交换速率，这种交换速率与蛋白质浓度及pH值有关。酰胺质子浓度越高，交换速率越快，APT信号强度越高；pH值越低，交换速率越慢，APT信号强度越低[5]。本研究建立新生猪急性缺氧缺血模型以模拟新生儿缺氧缺血脑损伤(hypoxic-ischemic brain injury， HIBI)病理变化，应用APT成像分析HI后新生猪脑内APT值的变化，以期为今后进一步临床无创评估脑内pH变化提供实验数据支持。

1 材料与方法

1.1 实验动物 选用出生后3～5天的健康Yorkshire猪共41只(由我院实验动物中心提供)，雌雄不限，体质量1.0～1.5 kg，平均(1.37±0.24)kg。排除中途死亡、建模失败及运动伪影等6只后，共35只新生猪纳入研究，随机分为对照组(n=5)和模型组(n=30)；模型组中又根据HIBI至MR扫描的间隔时间进一步分为6个时间亚组，即0～<2 h、2～<6 h、6～<12 h、12～<24 h、24～<48 h、48～<72 h亚组，每一亚组中各5只。本研究经我院医学伦理委员会审核(批号：2015PS337K)，对所有实验动物均严格执行《实验动物管理条例》和《实验动物许可证管理办法》的规定。

1.2建立HIBI实验模型

1.2.1 模型组 实验室内温度保持在28～30℃，以0.6 ml/kg体质量肌肉注射速眠新(长春军事医学院兽医研究所)麻醉实验猪后，行气管插管(直径2.5 mm)。……