Use of Radiological Clips for Improving Quantitative Ultrasound Imaging

项目摘要 放射标志物或夹子是一种基本的诊断和手术工具。钛制放射学夹子 或黄金被广泛使用，与MRI兼容，并已被证明在人类患者中使用是安全的。这些夹子来了 有多种形状和大小，用X射线和超声波都能看到。这些夹子提供了大型超声波 散射信号是因为它们是由金或钛制成的，它们与组织有很大的阻抗不匹配。 例如，接受新辅助化疗的局部晚期乳腺癌(LABC)患者 在肿瘤内放置夹子，以便外科医生能够准确地定位和切除残留的癌组织。 在过去的15年里，我们一直在开发定量超声(QUS)成像技术，以 一些应用，包括监测治疗反应。我们已经演示了QUS技术 可以检测肿瘤对治疗的反应，因为QUS对细胞死亡的存在很敏感。最近， 我们能够在一项小型临床研究中实施这种方法，在那里我们展示了qus的能力。 明确检测和预测LABC患者在一至四周内对化疗的反应 治疗开始了。我们验证了QUS可以识别LABC治疗应答者和无应答者。 然而，我们假设人类QUS估计的准确性可以通过以下方式显著提高 结合使用适当的放射学夹作为原位校准的新的校准程序 目标。临床上，这些夹子已经被放置在肿瘤内，用于各种诊断任务。通过插入一个 适当类型的夹子，该夹子可用作为QUS提供参考信号的原位校准 估计。现场基准将自动校正覆盖引起的衰减和传输损耗 组织层。目前的参考体模技术在提供衰减校正方面是不完整的 传输损耗。因此，使用适当的放射学夹子作为校准目标将提供 QUS估计的卓越偏差和方差提高了识别LABC反应的准确性。 拟议研究的科学前提是放射标志物用于X射线和常规 超声也可用作改善体内QUS估计的原位校准靶点。新颖的校准方法 这些程序将在体模研究、癌症动物模型中进行测试和改进，并最终在 应用定量超声识别乳腺癌新辅助化疗患者的早期疗效 心理治疗。为了验证这一科学前提，我们提出了三个具体目标。1)就地开发和提炼 模体研究中的校准方法，考虑了QUS估计的分层效应，从而改进了 QUS估计的准确性。2)在肿瘤动物模型上验证原位定标方法，并定量 纵向研究中的校准特性。3)在早期时间点收集纵向QUS患者数据 使用一种新的原位校准程序进行新辅助化疗的疗程并量化 采用现场校准法提高QUS分级机的精度。

Project Summary Radiological markers or clips are an essential diagnostic and surgical tool. Radiological clips made of titanium or gold are widely used, compatible with MRI and have proven safe for use in human patients. These clips come in many shapes and sizes and are visible with both X-ray and ultrasound. The clips provide large ultrasonic scattering signals because they are made of gold or titanium, which have large impedance mismatch with tissue. For example, patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy have clips placed in the tumors so that surgeons can locate and excise, with accuracy, residual cancer tissue. Over the last fifteen years, we have been developing quantitative ultrasound (QUS) imaging techniques for a number of applications including monitoring of therapy response. We have demonstrated that QUS techniques can detect the response of tumors to therapy because QUS is sensitive to the presence of cell death. Recently, we were able to implement this approach in a small clinical study, where we demonstrated the ability of QUS to definitively detect and predict the response of LABC patients to chemotherapy between one and four weeks from therapy onset. We verified that QUS could identify LABC therapy responders and nonresponders. However, we hypothesize that accuracies of QUS estimates in humans can be dramatically improved by incorporating a novel calibration procedure that utilizes appropriate radiological clips as an in situ calibration target. Clinically, these clips are already being placed in tumors for various diagnostic tasks. By inserting an appropriate type of clip, the clip can be used as an in situ calibration providing a reference signal for QUS estimates. The in situ reference will automatically correct for attenuation and transmission losses from overlying tissue layers. Current reference phantom techniques are incomplete in providing corrections for attenuation and transmission losses. Therefore, the use of appropriate radiological clips as calibration targets will provides superior bias and variance of QUS estimates resulting in improved accuracy for identifying LABC response. The scientific premise of the proposed research is that radiological markers used for X-ray and conventional ultrasound can also be used as an in situ calibration target for improving QUS estimates in vivo. Novel calibration procedures will be tested and refined in phantom studies, in animals models of cancer and finally validated in human breast cancer patients undergoing neoadjuvant chemotherapy using QUS to identify early responders to therapy. To verify this scientific premise we propose three specific aims. 1) Develop and refine an in situ calibration approach in phantom studies that accounts for layering effects on QUS estimates thereby improving QUS estimate accuracy. 2) Validate the in situ calibration approach in animal models of cancer and quantify calibration properties in a longitudinal study. 3) Collect longitudinal QUS patient data at early time points during the course of neoadjuvant chemotherapy using a novel in situ calibration procedure and quantify the improvements of QUS classifier accuracy with the in situ calibration approach.