Imaging Feedback to Guide Ultrasonic Tissue Fractionation for Cancer Therapy

描述(申请人提供)：组织学是在影像引导下，有控制地使用超声波空化来无创地机械分割组织体积。通过对气泡云启动和消退动力学的适当了解，可以在正常组织和受影响组织之间以非常窄的边界分割出精确的组织体积。由于分离发生在组织、细胞和分子水平，结果很容易被超声波和磁共振成像所看到。此外，分级的程度与处理体积中细胞的存活有关。随着分馏(或液化)的进行，背向散射声的数量减少，细胞存活率也随之下降。最终，当组织被高度分离时，即使用电子显微镜也无法观察到可识别的细胞器，均质组织看起来像是一种液体，几乎没有剩余的超声散射颗粒。由于组织摩擦的效果在治疗期间和治疗后的标准图像中都很明显，因此开发基于图像的反馈方案将图像参数与最终临床结果相关联的机会是显而易见的。与许多其他消融技术不同，这里提出的基于成像的反馈方法现在可以在合理的基础上开发，因为组织效应可以很容易地通过组织学分析和慢性动物研究来观察和表征，在这些研究中可以确定一些临床“结果”。因此，我们将开发方法，根据治疗过程中和治疗后可用的图像参数来预测临床结果。这将为大多数非侵入性消融技术提供一个关键问题的答案，即治疗应该在什么时候停止，所需治疗的空间范围是多少？这些图像引导技术的发展可能导致消融治疗在广泛的临床应用中的有效性发生重大变化，例如前列腺癌、良性前列腺增生症(BPH)、乳腺癌、乳腺纤维腺瘤、肝癌和转移瘤、肾癌、子宫肌瘤、溶栓、心脏消融术控制心律失常、肺癌和脑癌(在一定条件下)、感染伤口和脓肿的治疗等。

DESCRIPTION (provided by applicant): Histotripsy is the controlled use of ultrasound cavitation to mechanically fractionate tissue volumes noninvasively under image guidance. With an appropriate understanding of the dynamics of bubble cloud initiation and extinction, a precise volume of tissue can be fractionated with very narrow boundaries between normal and affected tissue. Since the fractionation occurs at the tissue, cellular, and molecular levels, the results are easily seen by both ultrasound and MR imaging. Moreover, the degree of fractionation is correlated with survival of cells in the treated volume. As fractionation (or liquefaction) progresses, the amount of backscattered sound decreases as well a cell survival. Eventually, when the tissue is highly fractionated, no recognizable cellular organelles can be observed, even with electron microscopy, and the homogenized tissue looks like a fluid with few remaining ultrasound scattering particles. Since the effects of histotripsy are apparent in standard images both during and after treatment, the opportunity to develop image based feedback schemes correlating image parameters with eventual clinical outcomes is obvious. Unlike many other ablation techniques, the imaging based feedback approaches proposed herein can now be developed on a rational basis since the tissue effects can be easily seen and characterized by histological analysis and chronic animal studies where some clinical "outcome" can be determined. Thus, we will develop methods to predict clinical outcome from image parameters available both during and after treatment. This will provide an answer to the critical question for most noninvasive ablative technologies, i.e., when should the treatment be stopped and what will be the spatial extent of the desired treatment? Development of these image guidance techniques could result in a significant transformation in the effectiveness of ablative therapies in a wide range of clinical applications, e.g., prostate cancer, benign prostatic hyperplasia (BPH), breast cancer, fibroadenomas of the breast, liver cancer and metastases, kidney cancer, uterine fibroids, thrombolysis, cardiac ablations for arrhythmia control, lung and brain cancer (under certain conditions), treatment of infected wounds and abscesses, etc.