Miller Douglas L, Lu Xiaofang, Fabiilli Mario, Dou Chunyan
Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA.
Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA.
Ultrasound Med Biol. 2019 Jan;45(1):170-176. doi: 10.1016/j.ultrasmedbio.2018.09.011. Epub 2018 Oct 23.
Recent research has found that contrast-enhanced diagnostic ultrasound (CEDUS) has the potential to induce localized injury in the liver, with clearly observable effects for contrast agent doses higher than the recommended dose and maximal mechanical index values. This study was undertaken to assess effects with intermittent exposure at lower contrast doses of infusion and at reduced output to determine thresholds. In addition, microbubble (MB) suspensions with enhanced content of larger MBs were tested. Exposure from a phased array probe (GE Vivid 7 Dimension, GE Vingmed Ultrasound, Horten, Norway) was applied at 1.6 MHz and 1-s intermittent frame trigger for 10 min with infusion of MB suspension with normal (1.8 µm), medium (3.1 µm) and large (5.3 µm) mean MB diameters. The bio-effect endpoint was the count of hepatocytes stained with Evans blue dye in frozen sections. For the normal MBs, the count increased for clinically relevant infusion dosages, but leveled off above 20 µL/kg/min. The evidence of injury declined with time from 30 min to 4 h and was lacking at 24 h. The exposure thresholds in terms of peak rarefactional pressure amplitude, divided by the square root of frequency (in situ mechanical index) were 1.7, 1.3 and 1.2 for the normal-, medium- and large-sized MB suspensions. The enhanced efficacy for larger MBs lends support to the two-criterion model for cavitational microvascular injury during CEDUS. Overall, CEDUS in liver appears to have markedly less potential for induction of tissue injury than has been reported in other tissues, which indicates a satisfactory safety profile for CEDUS using recommended parameters in normal liver.
最近的研究发现，超声造影诊断（CEDUS）有可能在肝脏中诱发局部损伤，对于高于推荐剂量和最大机械指数值的造影剂剂量，其影响清晰可见。本研究旨在评估在较低造影剂剂量输注和较低输出功率下间歇性暴露的影响，以确定阈值。此外，还测试了具有更高比例较大微泡（MB）的MB悬浮液。使用相控阵探头（GE Vivid 7 Dimension，GE Vingmed Ultrasound，挪威霍滕），以1.6 MHz频率和1秒间歇性帧触发，施加10分钟，同时输注平均MB直径为正常（1.8 µm）、中等（3.1 µm）和大（5.3 µm）的MB悬浮液。生物效应终点是冷冻切片中用伊文思蓝染料染色的肝细胞计数。对于正常MB，在临床相关输注剂量下计数增加，但在高于20 µL/kg/min时趋于平稳。损伤证据在30分钟至4小时内随时间下降，24小时时不存在。就峰值稀疏压力幅度除以频率平方根（原位机械指数）而言，正常、中等和大型MB悬浮液的暴露阈值分别为1.7、1.3和1.2。较大MB的增强功效支持了CEDUS期间空化微血管损伤的双标准模型。总体而言，肝脏中的CEDUS诱导组织损伤的潜力似乎明显低于其他组织中所报道的，这表明在正常肝脏中使用推荐参数的CEDUS具有令人满意的安全性。
