Three-Dimensional Multi-Parametric Ultrasound for Monitoring Therapy of Liver Metastasis

项目概要/摘要 非侵入性地预测或监测早期患者对癌症治疗的反应的能力将具有显著的临床意义。 对患者护理的影响，有可能使无应答患者免于高发病率和成本 与失败的治疗有关。由于其广泛的可及性，缺乏辐射，相对较低的成本， 由于超声对肝脏具有良好的可视化效果，因此是一种经证实的潜在理想模式， 在治疗过程中对患者的反应进行成像和监测。在第一阶段，我们 表明，目前的2D动态对比增强超声（DCE-US）从根本上限制了 由于肿瘤的异质性而导致量化，导致连续的采样误差，并出现大量过度或过度 低估患者的治疗反应。然后我们证明了这些局限性是可以克服的 通过使用创新矩阵阵列换能器技术的新型3D DCE-US成像方法， 运动补偿，准确的定量和体积评估肝转移瘤的组织灌注。 在这一竞争性的续约提案中，作为与飞利浦的行业-学术合作伙伴关系， 致力于我们的建议，我们的目标是临床推进3D多参数组织和灌注 超声表征（3D MPUS）预测或监测转移性乳腺癌患者的早期反应 结直肠癌转移至肝脏（mCRC）。为此，我们提出了一系列具体目标，我们将： 与Philips合作，增强3D DCE-US数据采集，以克服先前报告的局限性， 同时采集原始RF/B模式数据用于组织表征，并开发分析软件 适合于MPUS定量，ii）实现多位点临床可行性、采集可重复性和 300名患者中3D MPUS的定量再现性评估，以及iii）确定3D MPUS是否 定量可以预测或监测早期治疗反应。为此，基线和肿瘤的早期变化 灌注和组织参数（在治疗开始前和治疗开始后2-3周获得）将相互关联 治疗反应。根据2个月时获得的腹部放射学扫描确定的治疗反应 将使用标准RECIST 1.1报告来确定治疗开始后的时间。我们的建议建立在 最近FDA批准了用于肝肿瘤成像的超声造影剂， 商业3D US腹部探头，以及我们对3D DCE-US和广泛的 在QUS的经验。

PROJECT SUMMARY/ABSTRACT The ability to non-invasively predict or monitor early patient response to cancer therapy will have significant implications for patient care with the potential to spare non-responding patients the high morbidity and cost associated with failed treatments. Due to its wide accessibility, lack of radiation, relatively low cost, and excellent visualization of the liver, ultrasound is a demonstrated and potentially ideal modality to repeatedly image and monitor patient responses over the course of therapy. In the first phase of this work, we demonstrated that current 2D dynamic contrast-enhanced ultrasound (DCE-US) is fundamentally limited in quantification due to tumor heterogeneities, resulting in consecutive sampling errors with substantial over- or underestimation of treatment response in patients. We then showed that these limitations could be overcome by a novel 3D DCE-US imaging approach using innovative matrix array transducer technology to provide motion-compensated, accurate quantitative and volumetric assessment of tissue perfusion of liver metastases. In this competitive renewal proposal, framed as an industry-academic partnership with Philips who is committed to our proposal, our aim to clinically advance 3D multi-parametric tissue and perfusion characterization with ultrasound (3D MPUS) to predict or monitor early response in patients with metastatic colorectal cancers to the liver (mCRC). For this, we have proposed a set of specific aims where we will: i) work with Philips to enhance 3D DCE-US data acquisition to overcome previously reported limitations, enable simultaneous acquisition of raw RF/Bmode data for tissue characterization, and develop an analysis software suite for MPUS quantification, ii) carry-out a multi-site clinical feasibility, acquisition repeatability and quantification reproducibility assessment of 3D MPUS in 300 patients, and iii) determine whether 3D MPUS quantification can predict or monitor early therapy response. For this, baseline and early changes of tumor perfusion and tissue parameters (obtained before and at 2-3 weeks after initiation of therapy) will be correlated to treatment response. Treatment response as defined on abdominal radiological scans acquired at 2 months following treatment initiation will be determined using standard RECIST 1.1 reporting. Our proposal builds on the recent FDA approval of ultrasound contrast agents for liver tumor imaging, increased clinical availability of commercial 3D US abdominal probes, and our initial clinical validation of 3D DCE-US and extensive experiences in QUS.