Ultrasound-based tumor targeting and thermal ablation monitoring system

描述(申请人提供)：乳腺癌是美国女性中第二常见的癌症，也是第二大癌症杀手。由于医学成像的最新进展，有效的乳腺癌筛查和早期发现降低了乳腺癌的发病率。由于在早期阶段成功地发现了乳腺癌，治疗技术也有所改进。消融技术的前提是，如果肿瘤及其正常组织边缘能够被原位摧毁，而不是被切除，那么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，那么使用局部治疗的结果可能更有利。因此，随着高强度聚焦超声(HIFU)成为唯一真正的非侵入性、非电离的体外技术，消融技术在早期乳腺癌的治疗中逐渐成为侵入性较小、但同样有效的技术。HIFU已经被应用于治疗早期乳腺癌，没有复发或皮肤损伤(Huber等人。2001年；Hynynen等人。2001)。然而，将其移植到临床在一定程度上受到了基于磁共振的方法的极高成本和缓慢监测的阻碍，尽管它们的图像质量很高。因此，目前需要一种能够可靠地监测HIFU治疗的简单、经济高效的设备。为了保证HIFU监测的平移性和降低监测成本，同时保持HIFU的所有优势，我们开发了可与HIFU无缝结合用于肿瘤消融监测的谐和运动成像(HMI)辐射力技术，即聚焦超声(HMIFU)。因此，HMIFU是一种1)完全非侵入性(非接触式)，2)简单实施，3)实时，4)精确(估计1-10微米的位移)，5)完全集成，6)低成本的早期乳腺癌局部检测和原位热疗计划和监测的技术。这项研究的总体目标是开发、优化和测试实时HMIFU系统，利用肿瘤在体模、体外和活体小鼠和人体应用中加热过程中粘弹性性质的变化来进行肿瘤消融和监测。基本的假设是，与正常组织相比，肿瘤和热损伤具有足够不同的机械特性，因此该系统可以治疗和监测这种肿瘤的治疗。因此，拟议研究的具体目标是：1)实施全超声系统，用于在体模和手术后乳腺标本中实时热消融产生和监测和测试；2)应用HMIFU并在体内动物肿瘤模型中评估其性能；以及3)在活体人体乳腺癌受试者中论证初步的临床可行性。综上所述，HMIFU可以构成一种简单、无创、实时、低成本的乳腺良性肿瘤或早期肿瘤的监测技术。更重要的是，对于没有局限性局灶性疾病的妇女来说，它可能被证明是一个重要的选择，对她们来说，侵入性更小、更有针对性的治疗最有益，死亡率和风险都最低。

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.