长效循环顺磁性脂质体对比剂的磁共振对比增强血管成像

Contrast enhanced MR angiography using long-acting circulation paramagnetic liposomes

目的制备长效循环顺磁性脂质体,观察其理化特性并对健康大鼠进行对比增强磁共振血管造影。方法制备长效循环顺磁性脂质体对比剂,观察其理化特性。选择健康雄性SD大鼠20只,随机均分为两组,实验组静脉注射长效循环脂质体对比剂,对照组静脉注射Gd-DTPA。分别于注射对比剂前后即刻、15、30、45、60、75、90、120、180min对实验动物进行MR对比增强血管造影。选择原始图像中腹主动脉主干作为感兴趣区,测定增强扫描前后各个时间点的血管信号强度,计算信号增强百分比、对比度噪声比(CNR),绘制时间-强化曲线,并比较两组CNR的差异。结果长效循环顺磁性脂质体的R1弛豫率2.12/(mM.s)、平均粒径为123nm、多分散系数为0.29、克摩尔渗透系数280～305mOsm/kg水、Gd包封率约为41.37%。注射长效循环顺磁性循环脂质体后,血管表现为缓慢持久的强化,在注射对比剂后30min,信号强度达到最高,强化率约为116.29%,3h后强化率约为67.84%。对照组静注Gd-DTPA后即刻,腹主动脉的信号强度达到峰值,强化率约为185.90%,60min强化率仅为18.90%。在45～180min各时间点内,实验组的CNR较对照组显著增高。结论长效循环顺磁性脂质体可克服小分子对比剂快速弥散的缺点,具有优良的血池特性。

Objective To prepare long-acting circulation paramagnetic liposomes, in order to observe its physical and chemical properties through contrast-enhanced MR angiography of normal SD rats. Methods The long-acting circulation paramagnetic liposomes were prepared with hydrating a mixture with Gd-DTPA （Magnevist）. Then the physical and chemical properties was observed. Twenty SD rats were divided averagely into experimental group （long-acting circulation paramagnetic liposomes as contrast agent） and contrast group （Gd-DTPA as contrast agent）. Contrast enhanced MR angiography were performed before and at 0, 15, 30, 45, 60, 75, 90, 120, 180 min after injection of long-acting circulation paramagnetic liposomes and Gd-DTPA, respectively. The percentage of signal enhancement and contrast-to-noise ratio （CNR） of abdomi- nal aorta were calculated and the time-enhancement curve was drawn. CNR was compared between the two groups. Results The R1 relaxivity in vitro of long acting circulation paramagnetic liposomes was 2.12/（mM · s）. The mean intensity- weighted hydrodynamic diameter, polydisperisity index and osmolality were 123 nm, 0.29, and 280--305 mOsm/kg water, respectively. After injection of long-acting circulation paramagnetic liposomes, the signal intensity of abdominal aorta manifested as slow and sustained strengthening. The signal intensity reached the peak at 30 min after injection, the maximum enhancement rate was 116.29%, and the enhancement rate after 3 h was 67.84%. The signal intensity of abdominal aorta reached the peak immediately after injection of Gd DTPA in contrast group, and then decreased rapidly from its maximum enhancement of 185. 90% to 18.90% after 1 h. CNR of abdominal aorta in experimental group was significantly higher than that in contrast group from 45 min to 3 h after injection of contrast agent. Conclusion The long-acting circulation paramagnetic liposomes can overcome the defects of rapid diffusion of small molecular contrast agent and possess characteristics of excellent blood pool.