Ultrasound-based tumor targeting and thermal ablation monitoring system

描述（由申请人提供）：乳腺癌是美国女性第二大最常诊断的癌症，也是第二大癌症杀手。由于最近医学成像技术的进步，有效的乳腺癌筛查和早期发现降低了该疾病的发病率。由于在早期阶段成功地发现了乳腺癌，治疗技术也得到了改进。消融技术的前提是，如果肿瘤及其正常组织边缘可以被原位破坏，而不是被切除，对疾病的影响应该是相等的。此外，如果可以避免与手术干预相关的死亡率，那么使用局部治疗的结果可能更有利。因此，在早期乳腺癌的治疗中，消融技术逐渐成为侵入性较小但同样有效的技术，而高强度聚焦超声（HIFU）是唯一真正的无创、非电离、体外技术。HIFU已被应用于治疗无复发或皮肤损伤的早期乳腺癌（Huber et al. 2001; Hynynen et al. 2001）。然而，其向临床的转化一直受到阻碍，部分原因是使用的基于核磁共振的监测方法非常昂贵且速度缓慢，尽管它们的图像质量很高。因此，目前需要一种简单、经济的设备来可靠地监测HIFU治疗。为了保证其翻译，降低HIFU监测的监测成本，同时保持其所有优势，我们开发了谐波运动成像（HMI）的辐射力技术，可以与HIFU无缝结合用于肿瘤消融监测，即聚焦超声HMI （HMIFU）。因此，HMIFU是1)完全无创（非接触式），2)易于实现，3)实时，4)精确（估计位移1-10微米），5)完全可集成，6)低成本的早期乳腺癌局部检测和原位热处理计划和监测技术。本研究的总体目标是开发、优化和测试一种实时HMIFU系统，用于肿瘤消融和监测，该系统利用肿瘤在幻影、离体和体内小鼠和人类加热过程中黏弹性特性的变化进行评估。潜在的假设是，与正常组织相比，肿瘤和热损伤具有足够不同的机械特性，因此系统可以治疗和监测这种肿瘤的治疗。因此，该研究的具体目标是：1)实现一个全基于超声的实时热消融生成系统，并在虚幻和术后乳房标本中进行监测和测试；2)在动物肿瘤模型中应用HMIFU并评估其在体内的性能；3)在体内验证乳腺癌患者的初步临床可行性。总之，HMIFU是一种简单、无创、实时、低成本的良性或早期乳腺肿瘤监测技术。更重要的是，对于没有局限性局灶性疾病的妇女来说，这可能是一个重要的选择，对她们来说，侵入性更小、局灶性更强的治疗最有益，死亡率和风险最低。

DESCRIPTION (provided by applicant): Breast cancer is the second most frequently diagnosed cancer and the second cancer killer in U.S. women. Due to recent advances in medical imaging, efficient screening and early detection of breast cancer have resulted to lower morbidity from the disease. Because of the successful detection of breast cancer at an early stage, treatment techniques have also improved. The premise of ablation techniques is that, if a tumor and its normal-tissue margin can be destroyed in situ, instead of being removed, the impact on the disease should be equivalent. In addition, if the mortality associated with operative intervention can be avoided, then the outcome using localized treatments may be more advantageous. Ablation techniques are therefore slowly emerging as less invasive, but equally effective, in the treatment of early-stage breast cancer, with High-Intensity Focused Ultrasound (HIFU) being the only truly noninvasive, nonionizing, extracorporeal technique. HIFU has been applicable in the treatment of early-stage breast cancer with zero re-occurrence or skin damage (Huber et al. 2001; Hynynen et al. 2001). However, its translation to the clinic has been hindered in part by the extremely costly and slow monitoring MR-based methods used albeit their high image quality. Thus, there is currently a need for a simple, cost-efficient device that can reliably monitor HIFU treatment. In order to ensure its translation and reduce the cost of monitoring of HIFU monitoring while maintaining all its advantages, we have developed the radiation-force technique of Harmonic Motion Imaging (HMI) that can be used seamlessly in conjunction with HIFU for tumor ablation monitoring, namely HMI for Focused Ultrasound (HMIFU). HMIFU is thus an 1) entirely noninvasive (non-contact), 2) simple to implement, 3) real-time, 4) precise (estimating displacements of 1-10 microns), 5) fully integratable, and 6) low-cost technique for localized detection and in situ thermal treatment planning and monitoring of early-stage breast cancer. The general objective of the proposed study is to develop, optimize and test a real-time HMIFU system for tumor ablation and monitoring by utilizing the tumor's change in viscoelasticity property estimation during heating in phantom, ex vivo and in vivo murine and human applications. The underlying hypothesis is that the tumor and thermal lesion have sufficiently distinct mechanical properties compared to the normal tissue so that the system can treat and monitor the treatment of such a tumor. The specific aims of the proposed study are thus to: 1) implement an all ultrasound-based system for real-time thermal ablation generation and monitoring and test in phantom and post-surgical breast specimens; 2) apply HMIFU and assess its performance in animal tumor models in vivo; and 3) demonstrate initial clinical feasibility in human subjects with breast cancer in vivo. In summary, HMIFU can constitute a simple, noninvasive, real-time and low-cost monitoring technique for benign or early-stage breast tumors. More importantly, it may prove to be an important option to women without limited, focal disease, for whom less invasive and more focal treatment is most beneficial with minimized mortality and risk.