Ultrasound-based tumor targeting and thermal ablation monitoring system

基于超声的肿瘤靶向和热消融监测系统

• 批准号: 8205506
• 负责人: Elisa E. Konofagou
• 金额: $ 34.63万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8205506
• 关键词: Ablation; Address; Animals; Benign; Breast; Breast Cancer Detection; Breast Cancer Early Detection; Breast Cancer Treatment; Cancer Etiology; Cessation of life; Clinic; Clinical; Detection; Devices; Diagnostic Neoplasm Staging; Disease; Early treatment; Elasticity; Ensure; Evaluation; Fibroadenoma; Focused Ultrasound Therapy; General Anesthesia; Generations; Heating; Histopathology; Human; Image; In Situ; Intervention; Lesion; Magnetic Resonance Imaging; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Mammography; Mechanics; Medical Imaging; Methods; Monitor; Morbidity - disease rate; Motion; Mus; Neoplasm Metastasis; Normal tissue morphology; Operative Surgical Procedures; Outcome; Performance; Property; Radiation; Radiation therapy; Radiofrequency Interstitial Ablation; Real-Time Systems; Recurrence; Research; Resolution; Risk; Screening procedure; Second Primary Cancers; Skin; Skin Cancer; Solid; Specimen; Staging; System; Techniques; Testing; Thermal Ablation Therapy; Time; Tissues; Translations; Tumor stage; Ultrasonography; Woman; base; cancer diagnosis; chemotherapy; cost; design; falls; hormone therapy; human old age (65+); human subject; improved; in vivo; in vivo Model; infiltrating duct carcinoma; malignant breast neoplasm; mortality; mouse model; older women; patient population; response; treatment planning; tumor; viscoelasticity

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. PUBLIC HEALTH RELEVANCE: An ultrasound-based, integrated system will be optimized for real-time localization and monitoring of tumor ablation in vivo. This will constitute a simple, low-cost, noninvasive and real-time method for simultaneous, fast and effective tumor detection and treatment. This new method may prove to be an important option offered to older women with early-stage breast tumors.

描述（由申请人提供）：乳腺癌是美国妇女第二大最常见的癌症和第二大癌症杀手。由于医学成像的最新进展，乳腺癌的有效筛查和早期检测已经导致该疾病的发病率降低。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原位破坏，而不是被切除，对疾病的影响应该是等同的。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，消融技术逐渐成为治疗早期乳腺癌的微创但同样有效的技术，高强度聚焦超声（HIFU）是唯一真正无创、非电离的体外技术。HIFU已适用于治疗早期乳腺癌，无复发或皮肤损伤（Huber等人，2001; Hynynen等人，2001）。然而，尽管基于MR的方法图像质量很高，但其成本极高且监测缓慢，部分阻碍了其向临床的转化。因此，目前需要一种能够可靠地监测HIFU治疗的简单、成本有效的装置。为了确保其转化并降低HIFU监测的监测成本，同时保持其所有优势，我们开发了可以与HIFU无缝结合用于肿瘤消融监测的谐波运动成像（HMI）的辐射力技术，即聚焦超声（HMIFU）的HMI。因此，HHIFU是1）完全非侵入性（非接触式），2）实施简单，3）实时，4）精确（估计1-10微米的位移），5）完全可集成，以及6）用于早期乳腺癌的局部检测和原位热治疗规划和监测的低成本技术。拟议研究的总体目标是开发、优化和测试用于肿瘤消融和监测的实时高强度聚焦超声系统，该系统通过利用在体模、离体和体内小鼠和人类应用中加热期间肿瘤的粘弹性性质估计的变化。基本假设是，肿瘤和热损伤与正常组织相比具有足够不同的机械特性，使得系统可以治疗和监测这种肿瘤的治疗。因此，拟议研究的具体目的是：1）实现一种全超声系统，用于在体模和术后乳腺标本中进行实时热消融生成、监测和测试; 2）应用HIFU并评估其在体内动物肿瘤模型中的性能; 3）证明在患有乳腺癌的人类受试者体内的初步临床可行性。总之，高强度聚焦超声可以构成一种简单、无创、实时和低成本的监测技术，用于良性或早期乳腺肿瘤。更重要的是，它可能被证明是一个重要的选择，妇女没有有限的，局灶性疾病，对他们来说，侵入性较小，更集中的治疗是最有益的死亡率和风险最小化。 公共卫生相关性：将优化基于超声的集成系统，用于实时定位和监测体内肿瘤消融。这将构成一种简单、低成本、无创和实时的方法，用于同时、快速和有效的肿瘤检测和治疗。这种新方法可能被证明是为患有早期乳腺肿瘤的老年妇女提供的一种重要选择。