Vlaisavljevich Eli, Xu Zhen, Arvidson Alexa, Jin Lifang, Roberts William, Cain Charles
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Division of Pediatric Cardiology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
Ultrasound Med Biol. 2015 Nov;41(11):2938-54. doi: 10.1016/j.ultrasmedbio.2015.07.016. Epub 2015 Aug 28.
Histotripsy is a non-invasive ablation method that mechanically fractionates tissue by controlling acoustic cavitation. Previous work has revealed that tissue mechanical properties play a significant role in the histotripsy process, with stiffer tissues being more resistant to histotripsy-induced tissue damage. In this study, we propose a thermal pretreatment strategy to precondition tissues before histotripsy. We hypothesize that a thermal pretreatment can be used to alter tissue stiffness by modulating collagen composition, thus changing tissue susceptibility to histotripsy. More specifically, we hypothesize that tissues will soften and become more susceptible to histotripsy when preheated at ∼60°C because of collagen denaturation, but that tissues will rapidly stiffen and become less susceptible to histotripsy when preheated at ∼90°C because of collagen contraction. To test this hypothesis, a controlled temperature water bath was used to heat various ex vivo bovine tissues (tongue, artery, liver, kidney medulla, tendon and urethra). After heating, the Young's modulus of each tissue sample was measured using a tissue elastometer, and changes in tissue composition (i.e., collagen structure/density) were analyzed histologically. The susceptibility of tissues to histotripsy was investigated by treating the samples using a 750-kHz histotripsy transducer. Results revealed a decrease in stiffness and an increase in susceptibility to histotripsy for tissues (except urethra) preheated to 58°C. In contrast, preheating to 90°C increased tissue stiffness and reduced susceptibility to histotripsy for all tissues except tendon, which was significantly softened due to collagen hydrolysis into gelatin. On the basis of these results, a final set of experiments were conducted to determine the feasibility of using high-intensity focused ultrasound to provide the thermal pretreatment. Overall, the results of this study indicate the initial feasibility of a thermal pretreatment strategy to precondition tissue mechanical properties and alter tissue susceptibility to histotripsy. Future work will aim to optimize this thermal pretreatment strategy to determine if this approach is practical for specific clinical applications in vivo without causing unwanted damage to surrounding or overlying tissue.
组织粉碎术是一种通过控制声空化作用对组织进行机械破碎的非侵入性消融方法。先前的研究表明，组织的力学性能在组织粉碎术过程中起着重要作用，较硬的组织对组织粉碎术引起的组织损伤更具抵抗力。在本研究中，我们提出了一种热预处理策略，在组织粉碎术前对组织进行预处理。我们假设热预处理可通过调节胶原蛋白组成来改变组织硬度，从而改变组织对组织粉碎术的敏感性。更具体地说，我们假设组织在约60°C预热时会因胶原蛋白变性而变软，对组织粉碎术更敏感，但在约90°C预热时会因胶原蛋白收缩而迅速变硬，对组织粉碎术的敏感性降低。为了验证这一假设，使用控温水浴加热各种离体牛组织（舌头、动脉、肝脏、肾髓质、肌腱和尿道）。加热后，使用组织弹性仪测量每个组织样本的杨氏模量，并通过组织学分析组织组成的变化（即胶原蛋白结构/密度）。通过使用750kHz的组织粉碎术换能器处理样本，研究了组织对组织粉碎术的敏感性。结果显示，预热至58°C的组织（尿道除外）硬度降低，对组织粉碎术的敏感性增加。相比之下，预热至90°C会增加组织硬度，并降低所有组织（肌腱除外）对组织粉碎术的敏感性，肌腱因胶原蛋白水解成明胶而显著变软。基于这些结果，进行了最后一组实验，以确定使用高强度聚焦超声进行热预处理的可行性。总体而言，本研究结果表明热预处理策略在预处理组织力学性能和改变组织对组织粉碎术敏感性方面具有初步可行性。未来的工作将旨在优化这种热预处理策略，以确定该方法在体内特定临床应用中是否实用，而不会对周围或覆盖组织造成不必要的损伤。
