ULTRASOUND SAFETY WITH MIDFREQUENCY TRANSCRANIAL SONOTHROMBOLYSIS: PRELIMINARY STUDY ON NORMAL MACACA MONKEY BRAIN
ULTRASOUND SAFETY WITH MIDFREQUENCY TRANSCRANIAL SONOTHROMBOLYSIS: PRELIMINARY STUDY ON NORMAL MACACA MONKEY BRAIN
复制标题
DOI：
10.1016/j.ultrasmedbio.2012.02.009
复制
发表时间：
2012-06-01
影响因子：
2.9
通讯作者：
Furuhata, Hiroshi
中科院分区：
文献类型：
--
作者：
Shimizu, Jun;Fukuda, Takahiro;Furuhata, Hiroshi
我们研究了经颅靶向中频（0.1至1 MHz）超声溶栓治疗急性缺血性卒中的安全性。我们应用了一种新的治疗和成像换能器，健康的猕猴大脑，通过声处理同侧大脑中动脉通过声颞窗。将年轻的成年食蟹猴（Macaca fascicularis）分配到未超声处理的组（对照组）、超声处理后维持1 d的组（C1）和超声处理后维持7 d的组（C7;每组n = 3）。2只老年恒河猴（Macaca mulatta）在经静脉注射重组组织型纤溶酶原激活剂阿替普酶（0.9 mg/kg）的情况下进行超声处理，并维持7 d（R）。自动切换电路交替操作用于溶栓的治疗性超声波束（T-束）发生器（频率= 490 kHz;强度= 0.72 W/cm（2））和诊断性彩色血流成像超声波束（D-束;频率= 2.5 MHz;强度= 0.20 W/cm（2））。A 15分钟的协议，包括四个重复的序列120秒T-梁激活，然后30秒D-梁激活，然后5分钟T-梁失活连同D-梁激活，重复四次超过60分钟。确认神经功能缺损后，大脑被删除，并进行了组织学和免疫化学研究。对三个颅骨样本进行494 kHz连续波形超声，测量经颅强度并计算力学指数。在超声处理后，没有一只猴子表现出神经功能缺损。经颅超声强度率为48 +/-12%。颅内机械指数值为0.15。该新系统没有引起灵长类动物脑组织损伤，颅内也没有检测到空化效应。（电子邮件：jun-sh@jikei.ac.jp）（C）2012年世界医学和生物学超声联合会。
We investigated the safety of transcranial-targeting midfrequency (0.1 to 1 MHz) ultrasonic thrombolysis for acute ischemic stroke. We applied a new therapeutic and imaging transducer to healthy Macaca monkey brains via sonication of the ipsilateral middle cerebral artery through an acoustic temporal window. Young adult cynomolgus monkeys (Macaca fascicularis) were assigned to a group without sonication (control), a group maintained for 1 d after sonication (C1) and a group maintained for 7 d after sonication (C7; n = 3 for each). Two elder rhesus monkeys (Macaca mulatta) were ultrasonicated under transvenous injection of the recombinant tissue plasminogen activator alteplase (0.9 mg/kg), and maintained for 7 d (R). An automatic switching circuit alternately operated a therapeutic ultrasound beam (T-beam) generator for thrombolysis (frequency = 490 kHz; intensity = 0.72 W/cm(2)) and a diagnostic color-flow imaging ultrasound beam (D-beam; frequency = 2.5 MHz; intensity = 0.20 W/cm(2)). A 15-min protocol, comprising four repeats of a sequence of 120-s T-beam activation followed by 30-s D-beam activation and then 5-min T-beam deactivation together with D-beam activation, was repeated four times over 60 min. After confirmation of neurologic deficits, the brains were removed and investigated histologically and immunohistochemically. Three skull samples were subjected to 494-kHz continuous waveform ultrasound, the transcranial intensity was measured and the mechanical index was calculated. None of the monkeys showed neurologic deficits after ultrasonication. The transskull ultrasound intensity rate was 48 +/- 12%. The intracranial mechanical index value was 0.15. The novel system did not cause tissue damage in the primate brain and no cavitation effect was detected intracranially. (E-mail: jun-sh@jikei.ac.jp) (C) 2012 World Federation for Ultrasound in Medicine & Biology.