Chirp- and random-based coded ultrasonic excitation for localized blood-brain barrier opening.
Chirp- and random-based coded ultrasonic excitation for localized blood-brain barrier opening.
复制标题
DOI：
10.1088/0031-9155/60/19/7695
复制
发表时间：
2015-10-07
影响因子：
3.5
通讯作者：
Konofagou EE
中科院分区：
文献类型：
--
作者：
Kamimura HA;Wang S;Wu SY;Karakatsani ME;Acosta C;Carneiro AA;Konofagou EE
已经提出了基于线性调频和随机的编码激励方法，以减少驻波形成并改善经颅超声的聚焦。然而，没有明确的证据表明支持这些超声激励序列在体内的好处。本研究评价了啁啾和周期选择随机频率（PSRF）编码激发方法开放小鼠血脑屏障（BBB）的效果。给三组小鼠（n=15）注射多分散微泡，并使用chirp/PSRF编码（带宽：1.5-1.9 MHz，峰值负压：0.52 MPa，持续时间：30 s）或标准超声（频率：1.5 MHz，压力：0.52 MPa，爆发持续时间：20 ms，持续时间：5 min）序列在尾壳核中进行超声处理。采用T1加权增强MRI扫描对聚焦超声引起的血脑屏障开放进行定量分析。对于啁啾声、随机声和规则声处理，MRI评价的平均开口体积分别为9.38±5.71 mm 3、8.91±3.91 mm 3和35.47 ± 5.10 mm 3。啁啾声、随机声和规则声的平均空化水平分别为55.40±28.43 V.s、63.87±29.97 V.s和356.52±257.15 V.s。与常规超声处理技术的结果相比，啁啾和PSRF编码脉冲序列通过诱导较低的空化水平和较小的开口体积来改善BBB开口定位。较大的带宽与更集中的靶向相关，但受到换能器的频率响应、颅骨衰减和微泡最佳频率范围的限制。因此，编码方法可以促进高度局部化的药物递送，并使其他经颅超声技术受益，这些技术使用更高的压力水平和更高的精度来在大脑区域诱导必要的生物效应，同时避免对周围健康组织的损伤。
Chirp- and random-based coded excitation methods have been proposed to reduce standing wave formation and improve focusing of transcranial ultrasound. However, no clear evidence has been shown to support the benefits of these ultrasonic excitation sequences in vivo. This study evaluates the chirp and periodic selection of random frequency (PSRF) coded-excitation methods for opening the blood-brain barrier (BBB) in mice. Three groups of mice (n=15) were injected with polydisperse microbubbles and sonicated in the caudate putamen using the chirp/PSRF coded (bandwidth: 1.5-1.9 MHz, peak negative pressure: 0.52 MPa, duration: 30 s) or standard ultrasound (frequency: 1.5 MHz, pressure: 0.52 MPa, burst duration: 20 ms, duration: 5 min) sequences. T1-weighted contrast-enhanced MRI scans were performed to quantitatively analyze focused ultrasound induced BBB opening. The mean opening volumes evaluated from the MRI were 9.38±5.71 mm3, 8.91±3.91 mm3 and 35.47 ± 5.10 mm3 for the chirp, random and regular sonications, respectively. The mean cavitation levels were 55.40±28.43 V.s, 63.87±29.97 V.s and 356.52±257.15 V.s for the chirp, random and regular sonications, respectively. The chirp and PSRF coded pulsing sequences improved the BBB opening localization by inducing lower cavitation levels and smaller opening volumes compared to results of the regular sonication technique. Larger bandwidths were associated with more focused targeting but were limited by the frequency response of the transducer, the skull attenuation and the microbubbles optimal frequency range. The coded methods could therefore facilitate highly localized drug delivery as well as benefit other transcranial ultrasound techniques that use higher pressure levels and higher precision to induce the necessary bioeffects in a brain region while avoiding damage to the surrounding healthy tissue.