McDannold Nathan, Livingstone Margaret, Top Can Barış, Sutton Jonathan, Todd Nick, Vykhodtseva Natalia
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Phys Med Biol. 2016 Nov 7;61(21):7664-7687. doi: 10.1088/0031-9155/61/21/7664. Epub 2016 Oct 14.
This study investigated thermal ablation and skull-induced heating with a 230 kHz transcranial MRI-guided focused ultrasound (TcMRgFUS) system in nonhuman primates. We evaluated real-time acoustic feedback and aimed to understand whether cavitation contributed to the heating and the lesion formation. In four macaques, we sonicated thalamic targets at acoustic powers of 34-560 W (896-7590 J). Tissue effects evaluated with MRI and histology were compared to MRI-based temperature and thermal dose measurements, acoustic emissions recorded during the experiments, and acoustic and thermal simulations. Peak temperatures ranged from 46 to 57 °C, and lesions were produced in 5/8 sonicated targets. A linear relationship was observed between the applied acoustic energy and both the focal and brain surface heating. Thermal dose thresholds were 15-50 cumulative equivalent minutes at 43 °C, similar to prior studies at higher frequencies. Histology was also consistent with earlier studies of thermal effects in the brain. The system successfully controlled the power level and maintained a low level of cavitation activity. Increased acoustic emissions observed in 3/4 animals occurred when the focal temperature rise exceeded approximately 16 °C. Thresholds for thermally-significant subharmonic and wideband emissions were 129 and 140 W, respectively, corresponding to estimated pressure amplitudes of 2.1 and 2.2 MPa. Simulated focal heating was consistent with the measurements for sonications without thermally-significant acoustic emissions; otherwise it was consistently lower than the measurements. Overall, these results suggest that the lesions were produced by thermal mechanisms. The detected acoustic emissions, however, and their association with heating suggest that cavitation might have contributed to the focal heating. Compared to earlier work with a 670 kHz TcMRgFUS system, the brain surface heating was substantially reduced and the focal heating was higher with this 230 kHz system, suggesting that a reduced frequency can increase the treatment envelope for TcMRgFUS and potentially reduce the risk of skull heating.
本研究在非人灵长类动物中使用230kHz经颅MRI引导聚焦超声（TcMRgFUS）系统研究了热消融和颅骨诱导加热。我们评估了实时声学反馈，并旨在了解空化是否对加热和病变形成有影响。在4只猕猴中，我们以34 - 560W（896 - 7590J）的声功率对丘脑靶点进行超声处理。将通过MRI和组织学评估的组织效应与基于MRI的温度和热剂量测量、实验期间记录的声发射以及声学和热模拟进行比较。峰值温度范围为46至57°C，在8个超声处理的靶点中有5个产生了病变。观察到施加的声能与焦点和脑表面加热之间存在线性关系。热剂量阈值为43°C时15 - 50累积等效分钟，与先前更高频率的研究相似。组织学也与早期关于脑内热效应的研究一致。该系统成功控制了功率水平并维持了低水平的空化活动。当焦点温度升高超过约16°C时，在4只动物中的3只观察到声发射增加。热显著次谐波和宽带发射的阈值分别为129和140W，对应估计压力幅度为2.1和2.2MPa。模拟的焦点加热与无热显著声发射的超声处理测量结果一致；否则它始终低于测量值。总体而言，这些结果表明病变是由热机制产生的。然而，检测到的声发射及其与加热的关联表明空化可能对焦点加热有贡献。与早期使用670kHz TcMRgFUS系统的工作相比，该230kHz系统使脑表面加热大幅降低，焦点加热更高，这表明降低频率可增加TcMRgFUS的治疗范围，并可能降低颅骨加热的风险。
