IEEE Trans Biomed Eng. 2020 May;67(5):1387-1396. doi: 10.1109/TBME.2019.2936972. Epub 2019 Aug 22.
We previously developed short burst, phase keying (SBPK) focused ultrasound (FUS) to mitigate standing waves in the human vertebral canal. Here, we show microbubble emissions from these pulses can be detected through the human vertebral arch and that these pulses are effective for blood-spinal cord barrier (BSCB) opening.
At f = 514 kHz, circulating microbubbles were sonicated through ex vivo human vertebrae (60 kPa-1 MPa) using a dual-aperture approach and SBPK exposures engineered to incorporate pulse inversion (PI). Signals from a 250 kHz receiver were analyzed using PI, short-time Fourier analysis and the maximum projection over the pulse train. In rats (n = 14), SBPK FUS+microbubbles was applied to 3 locations/spinal cord at fixed pressures (∼0.20-0.47 MPa). MRI and histology were used to assess opening and tissue damage.
In human vertebrae between 0.2-0.4 MPa, PI amplified the microbubble/baseline ratio at f/2 and 2f by 202 ± 40% (132-291%). This was maximal at 0.4 MPa, coinciding with the onset of broadband emissions. In vivo, opening was achieved at 40/42 locations, with mean MRI enhancement of 46 ± 32%(16%-178%). Using PI, f/2 was detected at 14/40 opening locations. At the highest pressures (f/2 present) histology showed widespread bleeding throughout the focal region. At the lowest pressures, opening was achieved without bleeding.
This study confirmed that PI can increase sensitivity to transvertebral detection of microbubble signals. Preliminary in vivo investigations show that SBPK FUS can increase BSCB permeability without tissue damage.
SBPK is a clinically relevant pulse scheme and, in combination with PI, provides a means of mediating and monitoring BSCB opening noninvasively.
我们之前开发了短突发、相位键控（SBPK）聚焦超声（FUS）技术，以减轻人椎管中的驻波。在这里，我们展示了这些脉冲产生的微泡发射可以通过人体椎弓根检测到，并且这些脉冲对血脊髓屏障（BSCB）开放有效。
在 f = 514 kHz 下，使用双孔径方法和工程设计为包含脉冲反转（PI）的 SBPK 曝光，通过体外人椎骨（60 kPa-1 MPa）对循环微泡进行声处理。使用 PI、短时傅里叶分析和脉冲序列上的最大投影分析 250 kHz 接收器的信号。在大鼠（n = 14）中，将 SBPK FUS+微泡以固定压力（约 0.20-0.47 MPa）应用于 3 个位置/脊髓。使用 MRI 和组织学评估开放和组织损伤。
在 0.2-0.4 MPa 之间的人体椎骨中，PI 在 f/2 和 2f 处将微泡/基线比放大了 202 ± 40%（132-291%）。在 0.4 MPa 时达到最大值，此时出现宽带发射。在体内，在 40/42 个开放位置实现了开放，平均 MRI 增强 46 ± 32%（16%-178%）。使用 PI，在 14/40 个开放位置检测到 f/2。在最高压力（存在 f/2）下，组织学显示整个焦点区域广泛出血。在最低压力下，在没有出血的情况下实现了开放。
本研究证实，PI 可以提高经椎骨检测微泡信号的灵敏度。初步的体内研究表明，SBPK FUS 可以在不造成组织损伤的情况下增加 BSCB 的通透性。
SBPK 是一种具有临床相关性的脉冲方案，与 PI 结合使用，提供了一种非侵入性介导和监测 BSCB 开放的方法。
