Using Label-free Ultrasound Angio-Morphometry Analysis for Improving Ultrasound Specificity in Breast Cancer Detection and Treatment Monitoring

总结 乳腺肿块的活检前评估是选择正确的活检组的一个非常关键的步骤。 当前的成像方法，例如，乳房X光检查和超声检查（US）的特异性较低， 大量不必要的活检。在美国，可能不必要的活检的费用是 每年超过30亿美元，并因此给患者带来重大创伤和焦虑 侵入性手术另一个不确定的领域是评估术前化疗的反应， MRI由于价格高和难以获得而具有局限性，开发一种具有高 准确性是有保证的。 我们的愿景是补充超声与额外的定量成像信息的微血管形态 与疾病进展相关的信息。我们建议开发一种新型的成像生物标志物， 在不使用造影剂的情况下对微脉管系统形态进行可视化和量化，称为“标记- 免费的超声血管形态分析（LUAMA）”提供补充诊断和 常规US的预后信息。本研究的目标是将新工具LUAMA转化为 用于评估乳房肿块的临床工具。这项技术是基于新的处理和量化 使用高帧率超声成像来揭示和量化微脉管系统形态的程序。一个 这种技术的优点是它不需要使用造影剂来产生高分辨率 微血管的图像。我们计划解决乳腺癌的两个方面： 使用3D成像系统评估术前化疗反应， 微血管形态的估计。该项目包括2个具体目标：（1）确定诊断 LUAMA在活检前可疑乳腺肿块患者人群中的表现， 以病理学为金标准。(2)评估和预测术前对 使用LUAMA对乳腺癌患者进行化疗，并将结果与作为对照的MRI进行比较。这 该提案是该领域几位专家合作的结果，并受益于世界一流的 马约诊所的临床研究和设施。这项研究的成功完成将为 为临床乳腺癌患者提供了一种新技术。LUAMA是非侵入性的，成本低，易于使用， 与当前的美国技术兼容，这意味着该技术可以很容易地转化为临床， 广泛应用于乳腺癌患者。因此，这项研究有可能提供 显著影响乳腺癌诊断和减少不必要的活检，以及评估 对术前化疗的反应。

SUMMARY Pre-biopsy evaluation of breast masses is a very critical step in selecting the right group to be biopsied. Current imaging methods, e.g., mammography and ultrasound (US), carry low specificity rates that lead to a great number of unnecessary biopsies. In the United States, the cost of potentially unwarranted biopsies is more than $3 billion annually and associated with significant trauma and anxiety for the patients due to this invasive procedure. Another area of uncertainty is assessing response to preoperative chemotherapy, where MRI has limitation due to high price and inaccessibility, the development of an alternative method with high accuracy is warranted. Our vision is to complement US with additional quantitative imaging information of microvascular morphology that is relevant to disease progression. We propose to develop a new type of imaging biomarkers, based on visualization and quantification of microvasculature morphology without using contrast agents, called “Label- free Ultrasound Angio-Morphometry Analysis ((LUAMA)” to provide complementary diagnostic and prognostic information to conventional US. The goal of this research is to translate the new tool, LUAMA, as a clinical tool for assessment of breast masses. This technology is based on novel processing and quantification procedures to reveal and quantify microvasculature morphology using high frame rate ultrasound imaging. An advantage of this technique is that it does not require the use of contrast agents to produce high-resolution images of the microvasculature. We plan to address two aspects of breast cancer: identifying malignant masses and assessing preoperative chemotherapy response using 3D imaging system for a more accurate estimation of microvessel morphology. The project includes 2 specific aims: (1) Determine the diagnostic performance of LUAMA in a population of pre-biopsy patients with suspicious breast masses, correlate LUAMA results with pathology as the gold standard. (2) Assess and predict the response to preoperative chemotherapy in breast cancer patients using LUAMA and compare the results to MRI as control. This proposal is the result of collaboration among several experts in the field and benefits from the world-class clinical research and facilities at the Mayo Clinic. Successful completion of this research will open the door for a new technology for breast cancer patients in clinic. LUAMA is non-invasive, low cost, easy to use, and compatible with current US technology, which means that this technology can be readily translated to clinic and become available to a wide range of breast patients. Consequently, this research has potential to provide significant impact in breast cancer diagnosis and reducing unnecessary biopsies, as well as assessing response to preoperative chemotherapy.