Use of Radiological Clips for Improving Quantitative Ultrasound Imaging

项目摘要 放射标记物或夹子是一种重要的诊断和手术工具。钛制放射线夹 或金被广泛使用，与MRI兼容，并已被证明可安全用于人类患者。这些片段来自 有许多形状和大小，可以用X射线和超声波看到。夹子提供大的超声波 因为它们由金或钛制成，与组织具有较大的阻抗失配。 例如，接受新辅助化疗的局部晚期乳腺癌（LABC）患者， 在肿瘤中放置夹子，以便外科医生能够准确定位和切除残留的癌组织。 在过去的十五年里，我们一直在开发定量超声（QUS）成像技术， 许多应用包括监测治疗反应。我们已经证明，QUS技术 可以检测肿瘤对治疗的反应，因为QUS对细胞死亡的存在敏感。最近， 我们能够在一项小型临床研究中实施这种方法，我们证明了QUS的能力， 明确检测和预测LABC患者在化疗后1 - 4周内对化疗的反应， 开始治疗我们验证了QUS可以识别LABC治疗应答者和无应答者。 然而，我们假设通过以下方法可以显著提高人体QUS估计的准确性： 结合了一种新的校准程序，该程序利用适当的放射线夹作为原位校准 目标临床上，这些夹子已经被放置在肿瘤中用于各种诊断任务。通过插入 适当类型的夹子，夹子可用作原位校准，为QUS提供参考信号 估算现场参考将自动校正覆盖层的衰减和传输损耗 在组织的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，使用适当的放射线夹作为校准目标将提供 QUS估计值的上级偏倚和方差提高了识别LABC响应的准确性。 拟议研究的科学前提是，用于X射线和常规检查的放射性标记物 超声还可用作原位校准目标，以改善体内QUS估计。标定新 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 接受新辅助化疗的人乳腺癌患者使用QUS识别早期应答者， 疗法为了验证这一科学前提，我们提出了三个具体目标。1)开发和完善现场 体模研究中的校准方法，该方法解释了对QUS估计值的分层效应，从而改善了 QUS估计准确度。2)将原位校准方法应用于癌症动物模型， 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， 新辅助化疗的过程中使用一种新的原位校准程序，并量化 用原位校准方法提高QUS分类器的准确性。

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.