Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Ultrasound Med Biol. 2021 Jul;47(7):1747-1760. doi: 10.1016/j.ultrasmedbio.2021.03.007. Epub 2021 Apr 18.
Transient opening of the blood-spinal cord barrier has the potential to improve drug delivery options to the spinal cord. We previously developed short-burst phase-keying exposures to reduce focal depth of field and mitigate standing waves in the spinal canal. However, optimal short-burst phase-keying parameters for drug delivery have not been identified. Here, the effects of pressure, treatment duration, pulse length, burst repetition frequency and burst length on resulting tissue effects were investigated. Increased in situ pressures (0.23-0.33 MPa) led to increased post-treatment T-weighted contrast enhancement in magnetic resonance imaging (p = 0.015). Increased treatment duration (120 vs. 300 s) led to increased enhancement, but without statistical significance (p = 0.056). Increased burst repetition frequency (20 vs. 40 kHz) yielded a non-significant increase in enhancement (p = 0.064) but corresponded with increased damage observed on histology. No difference was observed in enhancement between pulse lengths of 2 and 10 ms (p = 0.912), corresponding with a sharp drop in the recorded second harmonic signal during the first 2 ms of the pulse. Increasing the burst length from two to five cycles (514 kHz) led to increased enhancement (p = 0.014). Results indicate that increasing the burst length may be the most effective method to enhance drug delivery. Additionally, shorter pulse lengths may allow more interleaved targets, and therefore a larger treatment volume, within one sonication.
短暂打开血-脊髓屏障有潜力改善脊髓内药物输送的选择。我们之前开发了短突发相位键控曝光技术，以减少焦深并减轻椎管内的驻波。然而，药物输送的最佳短突发相位键控参数尚未确定。在这里，研究了压力、治疗持续时间、脉冲长度、突发重复频率和突发长度对组织效应的影响。原位压力增加（0.23-0.33 MPa）导致磁共振成像（MRI）中治疗后 T 加权对比增强增加（p=0.015）。增加治疗持续时间（120 秒与 300 秒）导致增强增加，但无统计学意义（p=0.056）。增加突发重复频率（20 kHz 与 40 kHz）导致增强增加，但无统计学意义（p=0.064），但与组织学观察到的损伤增加相对应。脉冲长度为 2 毫秒与 10 毫秒之间的增强无差异（p=0.912），这与脉冲前 2 毫秒记录的二次谐波信号急剧下降相对应。将突发长度从两个周期增加到五个周期（514 kHz）导致增强增加（p=0.014）。结果表明，增加突发长度可能是增强药物输送最有效的方法。此外，较短的脉冲长度可以允许在一次超声处理中更交错的目标，因此治疗体积更大。
