Maleke C, Konofagou E E
Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Phys Med Biol. 2008 Mar 21;53(6):1773-93. doi: 10.1088/0031-9155/53/6/018. Epub 2008 Mar 7.
FUS (focused ultrasound), or HIFU (high-intensity-focused ultrasound) therapy, a minimally or non-invasive procedure that uses ultrasound to generate thermal necrosis, has been proven successful in several clinical applications. This paper discusses a method for monitoring thermal treatment at different sonication durations (10 s, 20 s and 30 s) using the amplitude-modulated (AM) harmonic motion imaging for focused ultrasound (HMIFU) technique in bovine liver samples in vitro. The feasibility of HMI for characterizing mechanical tissue properties has previously been demonstrated. Here, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) transducer, was used. The therapy transducer was driven by a low-frequency AM continuous signal at 25 Hz, producing a stable harmonic radiation force oscillating at the modulation frequency. A pulser/receiver was used to drive the pulse-echo transducer at a pulse repetition frequency (PRF) of 5.4 kHz. Radio-frequency (RF) signals were acquired using a standard pulse-echo technique. The temperature near the ablation region was simultaneously monitored. Both RF signals and temperature measurements were obtained before, during and after sonication. The resulting axial tissue displacement was estimated using one-dimensional cross correlation. When temperature at the focal zone was above 48 degrees C during heating, the coagulation necrosis occurred and tissue damage was irreversible. The HMI displacement profiles in relation to the temperature and sonication durations were analyzed. At the beginning of heating, the temperature at the focus increased sharply, while the tissue stiffness decreased resulting in higher HMI displacements. This was confirmed by an increase of 0.8 microm degrees C(-1)(r=0.93, p<.005). After sustained heating, the tissue became irreversibly stiffer, followed by an associated decrease in the HMI displacement (-0.79 microm degrees C(-1), r=-0.92, p<0.001). Repeated experiments showed a reproducible pattern of the HMI displacement changes with a temperature at a slope equal to 0.8+/-0.11 and -0.79+/-0.14 microm degrees C(-1), prior to and after lesion formation in seven bovine liver samples, respectively. This technique was thus capable of following the protein-denatured lesion formation based on the variation of the HMI displacements. This method could, therefore, be applied for real-time monitoring of temperature-related stiffness changes of tissues during FUS, HIFU or other thermal therapies.
聚焦超声（FUS）或高强度聚焦超声（HIFU）疗法是一种微创或无创的治疗方法，利用超声产生热坏死，已在多种临床应用中被证明是成功的。本文讨论了一种在体外牛肝样本中使用聚焦超声调幅（AM）谐波运动成像（HMIFU）技术监测不同超声处理持续时间（10秒、20秒和30秒）下热治疗的方法。HMI用于表征组织力学特性的可行性此前已得到证实。在这里，使用了一个共聚焦换能器，它结合了一个4.68MHz的治疗（FUS）换能器和一个7.5MHz的诊断（脉冲回波）换能器。治疗换能器由一个25Hz的低频AM连续信号驱动，产生一个以调制频率振荡的稳定谐波辐射力。一个脉冲发生器/接收器用于以5.4kHz的脉冲重复频率（PRF）驱动脉冲回波换能器。使用标准脉冲回波技术采集射频（RF）信号。同时监测消融区域附近的温度。在超声处理之前、期间和之后获取RF信号和温度测量值。使用一维互相关估计产生的轴向组织位移。当加热过程中焦点处的温度高于48摄氏度时，会发生凝固性坏死，组织损伤是不可逆的。分析了与温度和超声处理持续时间相关的HMI位移曲线。在加热开始时，焦点处的温度急剧上升，而组织硬度下降，导致HMI位移增加。这通过每升高0.8微摄氏度增加一次得到证实（r = 0.93，p <.005）。持续加热后，组织变得不可逆地变硬，随后HMI位移相应下降（-0.79微摄氏度，r = -0.92，p < 0.001）。重复实验表明，在七个牛肝样本中，在病变形成之前和之后，HMI位移变化与温度的模式具有可重复性，斜率分别为0.8 +/- 0.11和-0.79 +/- 0.14微摄氏度。因此，该技术能够根据HMI位移的变化跟踪蛋白质变性病变的形成。因此，该方法可用于在FUS、HIFU或其他热疗法期间实时监测组织与温度相关的硬度变化。
