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

描述（由申请人提供）：热消融和/或热疗是癌症治疗的重要治疗选择。非侵入性热技术治疗癌症的可能性在医学上具有非常重要的意义，因为它减少了对复杂和侵入性手术的需求。此外，它可能是一种非侵入性的技术来治疗肿瘤，否则无法通过传统的侵入性手段。高强度聚焦超声（HIFU）已被建议作为一种 涉及非侵入性热消融或热疗的临床治疗的可能技术。HIFU允许在热消融或热疗治疗中靶向小区域。高强度聚焦超声已在癌症动物模型和有限的临床研究中得到成功证实。然而，目前的无创成像技术阶段，监测和评估HIFU治疗在体内的范围和及时性有限。如果能够发展一种稳健的、无创的成像方法来分期、监测和评估HIFU治疗，将大大提高HIFU的临床医学意义。拟议研究的长期目标是开发和验证基于定量超声（QUS）模型的成像技术，该技术将允许对体内肿瘤的HIFU治疗进行无创分期、监测和评估。为了实现本研究的长期目标，提出了以下具体目标：1）开发一种基于QUS模型的技术，以分期和评估使用HIFU治疗实体瘤和生物幻影。2)开发使用QUS模型成像和相干反向散射监测实体瘤HIFU治疗的技术。3)使用模拟和真实的生物体模评价分期、监测和评估HIFU治疗的技术。4)介绍了肿瘤动物模型中HIFU治疗的分期、监测和评估技术。为了开发和验证用于肿瘤分期、监测和评估HIFU治疗的基于QUS模型的成像，将实施以下计划。首先，从癌症动物模型的三种肿瘤的组织学分析将被用来构建散射的超声模型。从这些超声模型中，QUS参数预计将产生显着的信息，用于分类和评估肿瘤后，HIFU治疗将推导。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，以监测治疗期间的温度沉积。第三，该技术将被优化，并且基于QUS模型的成像的空间分辨率将通过对经历HIFU治疗的真实的生物体模的模拟和实验来确定。最后，通过建模、仿真和生物体模实验开发的基于QUS模型的成像技术将通过对三种癌症动物模型进行HIFU治疗来验证。将通过与组织学比较，评价QUS基于模型的成像在动物模型中分期、监测和评估HIFU治疗的能力。 公共卫生相关性声明（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临床治疗技术，涉及癌症的无创热消融或热疗。目前，分期、监测和评估体内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。在该提案中，将开发基于定量超声（QUS）模型的成像技术，该技术对组织中的微观结构变化敏感，并且可用于非侵入性地分期、监测和评估体内超声诱导的热疗或HIFU消融肿瘤。

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.