| 罗凯旋,王钰宏,宋宇婷,井治聪,陈茉弦,敖丽娟.经颅聚焦超声开放小鼠血脑屏障的脉宽筛选及可逆性研究[J].中国康复医学杂志,2023,(2):151~158 |
| 经颅聚焦超声开放小鼠血脑屏障的脉宽筛选及可逆性研究 点此下载全文 |
| 罗凯旋 王钰宏 宋宇婷 井治聪 陈茉弦 敖丽娟 |
| 昆明医科大学康复学院，云南省昆明市，650500 |
| 基金项目：国家自然科学基金(81660381，81960421)； 云南省教育厅科学研究基金(2020Y0139) |
| DOI：10.3969/j.issn.1001-1242.2023.02.003 |
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| 摘要： |
| 摘要
目的：利用聚焦超声(focused ultrasound， FUS)治疗系统，固定基础频率等其他参数，探索脉宽对FUS经颅开放血脑屏障(BBB)有效性及安全性的影响，筛选出合适的脉宽值，并验证FUS开放BBB的可逆性。
方法：将73只SPF级昆明小鼠，随机分为脉宽筛选组(共45只)和可逆性研究组(28只)。脉宽筛选组又分为0ms组、1ms组、10ms组、100ms组和200ms组共5个亚组，用不同脉宽的FUS经颅辐照靶脑区后经尾静脉注射伊文思蓝(Evans blue， EB)溶液，4h后取材，对BBB开放与否进行定性评价并测量脑组织EB含量，辐照区域脑组织行HE染色；可逆性研究组分为4个亚组(每组7只)：-1—0h组、0—1h组、1—8h组和8—9h组，分别于相应时间点进行FUS经颅辐照、EB注射，取材，对脑部EB含量进行测量。
结果：0ms组小鼠BBB未开放，小鼠脑部EB含量为（4.67±2.14）μg/g，其余各组小鼠BBB均有不同程度开放。1ms、10ms、100ms、200ms组小鼠脑部EB含量分别为（9.63±3.31）μg/g、（19.16±2.47）μg/g、（20.75±7.77）μg/g、（29.48±10.42）μg/g，其中1ms、10ms、100ms、200ms组小鼠脑部EB含量与对照组(0ms组)相比有显著性意义，且10、100、200ms组BBB开放效率明显高于1ms组。0ms组、1ms组、10ms组小鼠FUS辐照中心区域脑组织未见红细胞渗出，100ms组、200ms组FUS辐照中心区域有少量红细胞渗出；-1—0h组、8—9h组小鼠BBB未开放，0—1h组、1—8h组小鼠BBB有不同程度开放。-1—0h组、0—1h组、1—8h组、8—9h组小鼠脑部EB含量分别为（1.50±0.19）μg/g、（8.60±1.89）μg/g、（2.63±0.76）μg/g、（1.57±0.46）μg/g。与对照组相比，0—1h组、1—8h组小鼠脑部EB含量明显增高。8—9h组与对照组相比无显著性意义，同时，0—1h组与其他各组相比均有显著性意义。
结论：利用现有聚焦超声治疗系统，当FUS基础频率为1MHz，总辐照时间120s，输出电压200mV，脉冲重复频率为1Hz，SonoVue?六氟化硫微泡剂量2.5μl/g情况下，脉宽10ms可经颅、高效、安全开放BBB，是较为合适的脉宽值。该参数条件下FUS开放BBB是动态可逆的。 |
| 关键词：血脑屏障 聚焦超声 微泡 可逆性 神经调控 |
| Screening out appropriate burst duration of transcranial focused ultrasound that mediated blood-brain barrier opening and exploring its reversibility Download Fulltext |
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| The School of Rehabilitation， Kunming Medical University， Kunming， 650500 |
| Fund Project: |
| Abstract: |
| Abstract
Objective： To explore the influence of burst duration on effectiveness and safety of opening the blood-brain barrier (BBB) by focused ultrasound (FUS)， to screen out the appropriate value of burst duration of focused ultrasound therapy system with other parameters fixed， and to explore the reversibility of FUS-mediated BBB opening.
Method： Seventy-three SPF male KM mice were randomly divided into burst duration groups(n=45) and reversibility exploring groups(n=28). Burst duration groups included 0ms group， 1ms group， 10ms group， 100ms group， 200ms group and were transcranially given FUS irradiation with corresponding burst duration. Evans blue(EB) was injected through the tail vein after FUS. The brain samples were collected 4h later. BBB opening state was observed and the content of EB in brain was measured， target brain region was hematoxylin-eosin(HE) stained. The reversibility exploring groups were divided into 4 subgroups(7 rats in each group)： ﹣1—0h group， 0—1h group， 1—8h group and 8—9h group. mice were subjected to transcranial FUS irradiation， EB injection and sampling were done at corresponding time points respectively. The EB content in the brain was measured.
Result： BBB of 0mV group stayed unopen， and the content of EB in the brain was （4.67±2.14）μg/g. BBB in the other groups were open to different degrees. EB contents in the brains of 1ms， 10ms， 100ms and 200ms groups were （9.63±3.31）μg/g， （19.16±2.47）μg/g， （20.75±7.77）μg/g and （29.48±10.42）μg/g, respectively. The EB contents of 1ms， 10ms， 100ms and 200ms group were statistically significant compared with that of the control group. The BBB opening efficiencies of the 10， 100， 200ms groups were remarkably higher than that of the 1ms group. No erythrocyte exudation in the brain tissue was observed within FUS sonicated area in the 0ms， 1ms and 10ms groups. As for the 100ms and 200ms groups， a small amount of red blood cells exudated in the sonicated brain tissue. The BBB of -1—0h and 8—9h groups stayed unopen. The BBB of 0—1h and 1—8h groups were open to different degrees. The EB contents in the brains of ﹣1—0h， 0—1h， 1—8h and 8—9h groups were （1.50±0.19）μg/g， （8.60±1.89）μg/g， （2.63±0.76）μg/g and （1.57±0.46）μg/g， respectively. Compared with the control group， the contents of EB in the brain of 0—1h and 1—8h groups were significantly higher. And there was no statistical significance between the 8—9h group and control group. There were statistical significances between the 0—1h group and other groups.
Conclusion： 10ms is an appropriate burst duration value to open the BBB. Under parameters of fundamental frequency 1MHz， total exposure time 120s， output voltage 200mV， pulse repetition frequency 1Hz， micro-bubble (SonoVue?) dose 2.5μl/g， the BBB can be opened transcranially， effectively， safely and reversibly when the burst duration is set to 10ms using existing FUS therapy system. |
| Keywords:blood-brain barrier focused ultrasound micro-bubbles reversibility neuromodulation |
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