Lin Kuang-Wei, Hall Timothy L, Xu Zhen, Cain Charles A
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Ultrasound Med Biol. 2015 Aug;41(8):2148-60. doi: 10.1016/j.ultrasmedbio.2015.03.026. Epub 2015 Apr 27.
When histotripsy pulses shorter than 2 cycles are applied, the formation of a dense bubble cloud relies only on the applied peak negative pressure (p-) exceeding the "intrinsic threshold" of the medium (absolute value of 26-30 MPa in most soft tissues). It has been found that a sub-threshold high-frequency probe pulse (3 MHz) can be enabled by a sub-threshold low-frequency pump pulse (500 kHz) where the sum exceeds the intrinsic threshold, thus generating lesion-producing dense bubble clouds ("dual-beam histotripsy"). Here, the feasibility of using an imaging transducer to provide the high-frequency probe pulse in the dual-beam histotripsy approach is investigated. More specifically, an ATL L7-4 imaging transducer (Philips Healthcare, Andover, MA, USA), pulsed by a V-1 Data Acquisition System (Verasonics, Redmond, WA, USA), was used to generate the high-frequency probe pulses. The low-frequency pump pulses were generated by a 20-element 345-kHz array transducer, driven by a custom high-voltage pulser. These dual-beam histotripsy pulses were applied to red blood cell tissue-mimicking phantoms at a pulse repetition frequency of 1 Hz, and optical imaging was used to visualize bubble clouds and lesions generated in the red blood cell phantoms. The results indicated that dense bubble clouds (and resulting lesions) were generated when the p- of the sub-threshold pump and probe pulses combined constructively to exceed the intrinsic threshold. The average size of the smallest reproducible lesions using the imaging probe pulse enabled by the sub-threshold pump pulse was 0.7 × 1.7 mm, whereas that using the supra-threshold pump pulse alone was 1.4 × 3.7 mm. When the imaging transducer was steered laterally, bubble clouds and lesions were steered correspondingly until the combined p- no longer exceeded the intrinsic threshold. These results were also validated with ex vivo porcine liver experiments. Using an imaging transducer for dual-beam histotripsy can have two advantages: (i) lesion steering can be achieved using the steering of the imaging transducer (implemented with the beamformer of the accompanying programmable ultrasound system), and (ii) treatment can be simultaneously monitored when the imaging transducer is used in conjunction with an ultrasound imaging system.
当施加短于2个周期的组织粉碎脉冲时，致密气泡云的形成仅依赖于所施加的峰值负压（p-）超过介质的“固有阈值”（大多数软组织中为26 - 30 MPa的绝对值）。研究发现，低于阈值的高频探测脉冲（3 MHz）可由低于阈值的低频泵浦脉冲（500 kHz）激发，只要二者之和超过固有阈值，从而产生可形成损伤的致密气泡云（“双束组织粉碎术”）。在此，研究了在双束组织粉碎术方法中使用成像换能器提供高频探测脉冲的可行性。更具体地说，使用由V - 1数据采集系统（Verasonics公司，美国华盛顿州雷德蒙德）激发的ATL L7 - 4成像换能器（飞利浦医疗保健公司，美国马萨诸塞州安多弗）来产生高频探测脉冲。低频泵浦脉冲由一个由定制高压脉冲发生器驱动的20阵元345 kHz阵列换能器产生。这些双束组织粉碎脉冲以1 Hz的脉冲重复频率施加于红细胞组织模拟体模上，并使用光学成像来观察红细胞体模中产生的气泡云和损伤。结果表明，当低于阈值的泵浦脉冲和探测脉冲的p-相长叠加超过固有阈值时，会产生致密气泡云（以及由此产生的损伤）。使用低于阈值的泵浦脉冲激发成像探测脉冲产生的最小可重复损伤的平均尺寸为0.7×1.7 mm，而单独使用高于阈值的泵浦脉冲时为1.4×3.7 mm。当成像换能器横向偏转时，气泡云和损伤会相应地偏转，直到组合的p-不再超过固有阈值。这些结果也通过离体猪肝实验得到了验证。在双束组织粉碎术中使用成像换能器有两个优点：（i）可以通过成像换能器的偏转（由随附的可编程超声系统的波束形成器实现）来实现损伤引导，并且（ii）当成像换能器与超声成像系统结合使用时，可以同时监测治疗情况。
