Use of quantitative ultrasound to stage, monitor, and assess HIFU treatment

描述(申请人提供)：热消融和/或热疗是癌症治疗的重要治疗选择。非侵入性热疗技术治疗癌症的可能性具有非常重要的医学意义，因为它减少了复杂和侵入性手术的需要。此外，非侵入性技术有可能治疗原本无法通过传统侵入性手段进行手术的肿瘤。高强度聚焦超声(HIFU)已被认为是一种 非侵入性热消融或热疗临床治疗的可能技术。HIFU允许在热消融或热疗中针对小区域。HIFU已经在癌症的动物模型和有限的临床研究中得到了成功的证明。然而，目前用于在体内分期、监测和评估HIFU治疗的非侵入性成像技术在范围和及时性方面都是有限的。如果能够开发一种稳健的、无创的成像方法来分期、监测和评估HIFU治疗，HIFU在临床医学中的意义将大大增强。这项拟议研究的长期目标是开发和验证一种基于定量超声(QUS)模型的成像技术，该技术将允许对体内肿瘤的HIFU治疗进行非侵入性分期、监测和评估。为了实现拟议研究的长期目标，提出了以下具体目标：1)开发一种基于QUS模型的技术来利用HIFU对实体瘤和生物幻影的治疗进行分期和评估。2)开发使用基于QUS模型的成像和相干背向散射来监测HIFU治疗实体肿瘤的技术。3)使用模拟和真实生物模型评估HIFU治疗的分期、监测和评估技术。4)在癌症动物模型中验证用于分期、监测和评估HIFU治疗的技术。为了开发和验证基于QUS模型的成像用于肿瘤的分期、监测和评估，将实施以下计划。首先，我们将利用肿瘤动物模型中的三种肿瘤的组织学分析来构建超声散射模型。从这些超声模型中，QUS参数有望为HIFU治疗后肿瘤的分类和评估提供重要信息。其次，将获得这些QUS参数在治疗期间如何变化的详细测量和估计，以便监测治疗期间的温度沉积。第三，通过对正在接受HIFU治疗的真实生物模型的模拟和实验，优化技术并确定基于QUS模型的成像的空间分辨率。最后，通过对三种肿瘤动物模型进行HIFU治疗，验证了通过建模、模拟和生物模体实验开发的基于QUS模型的成像技术。QUS模型成像在动物模型中分期、监测和评估HIFU治疗的能力将通过与组织学的比较来评估。 公共卫生相关声明(由申请人提供)：高强度聚焦超声(HIFU)已被建议作为一种可能的技术，用于非侵入性热消融或癌症热疗的临床治疗。目前，用于在体内分期、监测和评估HIFU治疗的非侵入性成像技术在范围和及时性方面受到限制，从而降低了该方法的临床实用性。在这项建议中，将开发一种基于定量超声(QUS)模型的成像技术，该技术对组织的微结构变化敏感，可用于体内肿瘤的超声热疗或HIFU消融的无创性分期、监测和评估。

DESCRIPTION (provided by applicant): Thermal ablation and/or hyperthermia are important treatment options for cancer therapy. The possibility of noninvasive thermal techniques for treating cancer is highly medically significant because it reduces the need for complicated and invasive surgery. In addition, it may be possible for a noninvasive technique to treat tumors that are otherwise inoperable through traditional invasive means. High intensity focused ultrasound (HIFU) has been suggested as a possible technique for clinical therapies involving noninvasive thermal ablation or hyperthermia. HIFU allows the targeting of small regions in thermal ablation or hyperthermia treatment. HIFU has been successfully demonstrated in animal models of cancer and in limited clinical studies. However, current noninvasive imaging techniques to stage, monitor, and assess HIFU treatment in vivo are limited in scope and timeliness. If a robust, noninvasive imaging method could be developed to stage, monitor, and assess HIFU treatment, the significance of HIFU to clinical medicine would be greatly enhanced. The long-term objective of the proposed research is to develop and validate a quantitative ultrasound (QUS) model-based imaging technique that will allow the noninvasive staging, monitoring, and assessment of HIFU treatment of tumors in vivo. To accomplish the long-term objective of the proposed research the following specific aims were proposed: 1) Develop a QUS model-based technique to stage and assess the treatment of solid tumors and biological phantoms using HIFU. 2) Develop techniques to monitor HIFU treatment of solid tumors using QUS model-based imaging and coherent backscatter. 3) Evaluate the techniques to stage, monitor, and assess HIFU treatment using simulations and real biological phantoms. 4) Validate the techniques to stage, monitor, and assess HIFU treatment in animal models of cancer. To develop and validate QUS model-based imaging for staging, monitoring, and assessing HIFU treatment of tumors the following plan will be implemented. First, histological analyses of three kinds of tumors from animal models of cancer will be used to construct ultrasonic models of scattering. From these ultrasonic models, QUS parameters expected to yield significant information for classifying and assessing tumors after HIFU treatment will be deduced. Second, detailed measurements and estimates of how these QUS parameters change during treatment will be obtained in order to monitor temperature deposition during treatment. Third, the technique will be optimized and spatial resolution of the QUS model-based imaging determined through simulations and experiments with real biological phantoms undergoing HIFU treatment. Finally, the QUS model-based imaging technique developed through modeling, simulations, and biological phantom experiments will be validated by conducting HIFU treatment on the three animal models of cancer. The ability of QUS model-based imaging to stage, monitor, and assess HIFU treatment in the animal models will be evaluated through comparisons with histology. Public Health Relevance Statement (provided by applicant): High intensity focused ultrasound (HIFU) has been suggested as a possible technique for clinical therapies involving noninvasive thermal ablation or hyperthermia of cancer. Currently, noninvasive imaging techniques to stage, monitor, and assess HIFU treatment in vivo are limited in scope and timeliness, thereby reducing the clinical utility of the approach. In this proposal a quantitative ultrasound (QUS) model based imaging technique will be developed that is sensitive to microstructural changes in tissues and can be used to noninvasively stage, monitor, and assess ultrasound induced hyperthermia or HIFU ablation of tumors in vivo.