3D Dynamic Contrast-Enhanced US for Monitoring Chemotherapy of Liver Metastasis

 描述（由申请人提供）：非侵入性预测哪些癌症患者将对化疗有反应的能力将对患者护理和公共卫生产生重大影响，有可能使无反应患者免于与这些治疗相关的高发病率和成本。因此，迫切需要新型的非侵入性成像技术来预测和/或早期评估治疗反应。由于其广泛的可及性，缺乏辐射，相对较低的成本，以及良好的可视化的生活，超声灌注成像后静脉注射造影剂微泡是一个有前途的新的功能模式，用于评估组织灌注的肝转移，最常见的部位转移的结直肠癌患者。然而，目前的二维动态对比增强超声（DCE-US），仅覆盖肿瘤体积的一小部分，从根本上限制了量化的三维（3D）异质性的肿瘤灌注，导致连续的采样误差与实质上高估或低估的治疗反应的DCE-US成像。这些局限性可以通过一种新的3D DCE-US成像方法来克服，该方法将创新的矩阵阵列换能器技术与实时电磁跟踪相结合，以提供对肝转移瘤组织灌注的运动补偿、准确的定量和体积评估。我们的总体目标是评估结直肠肝转移患者的3D DCE-US可重复性，并评估其预测治疗反应的能力。在50例新诊断为低级别结直肠腺癌肝转移的患者中，将通过使用我们在先前的小鼠人结肠癌异种移植物临床前实验中验证的破坏-补充DCE-US技术评估跟踪辅助3D DCE-US的再现性。然后将肿瘤灌注参数的基线和早期变化（在化疗开始前和化疗开始后2-3周获得）与以下终点相关：局部治疗缓解、无进展生存期和组织学。将使用RECIST 1.1报告作为参考标准，确定治疗开始后2个月获得的腹部CT扫描定义的治疗缓解。灌注参数的基线值和早期变化将与接受手术肝转移切除术的患者的CT结果和组织学相关。

 DESCRIPTION (provided by applicant): The ability to non-invasively predict which cancer patients will respond to chemotherapy will have significant implications for patient care and public health with the potential to spare non-responding patients the high morbidity and cost associated with these treatments. Therefore, novel non-invasive imaging technologies to allow both prediction and/or early evaluation of treatment response are critically needed. Due to its wide accessibility, lack of radiation, relatively low cost, and excellent visualization of the live, ultrasound perfusion imaging following intravenous administration of contrast microbubbles is a promising new functional modality for assessing tissue perfusion of liver metastases, the most common site of metastases in patients with colorectal cancer. However, current two-dimensional dynamic contrast-enhanced ultrasound (DCE-US), covering only a small fraction of the tumor volume, is fundamentally limited in quantification by the three-dimensional (3D) heterogeneity of tumor perfusion, resulting in consecutive sampling errors with substantial over- or underestimation of treatment response on DCE-US imaging. These limitations could be overcome by a novel 3D DCE-US imaging approach combining innovative matrix array transducer technology with real-time electromagnetic tracking to provide motion-compensated, accurate quantitative and volumetric assessment of tissue perfusion of liver metastases. Our overall goal is to assess 3D DCE-US reproducibility in patients with colorectal liver metastases and to evaluate its ability to predict treatment response. In 50 patients with newly diagnosed liver metastases from low grade colorectal adenocarcinoma, the reproducibility of tracking-assisted 3D DCE-US will be assessed by using a disruption-replenishment DCE-US technique which we had validated in previous preclinical experiments in human colon cancer xenografts in mice. Baseline and early changes of tumor perfusion parameters (obtained before and at 2-3 weeks after the initiation of chemotherapy) will then be correlated to the following endpoints: local treatment response, progression free survival, and histology. Treatment response as defined on abdominal CT scans acquired at 2 months following treatment initiation will be determined using RECIST 1.1 reporting as reference standard. Baseline values and early changes in perfusion parameters will be correlated with CT findings and with histology in patients undergoing surgical liver metastasis resection.