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

摘要 乳腺肿块的活检前评估是选择正确的活检对象的非常关键的步骤。 目前的成像方法，例如乳房X光照相和超声(美国)，特异性很低，导致 大量不必要的活组织检查。在美国，可能不必要的活检成本是 每年超过30亿美元，并因此而给患者带来严重的创伤和焦虑 侵入性手术。另一个不确定的领域是评估对术前化疗的反应， 由于价格昂贵和难以获得，MRI具有局限性，开发一种替代方法具有较高的成本 准确度是有保证的。 我们的愿景是用额外的微血管形态的定量成像信息来补充US 这与疾病的进展有关。我们建议开发一种新型的成像生物标记物，基于 在不使用造影剂的情况下，微血管形态的可视化和量化，称为“标记- 免费超声血管形态计量学分析((LUAMA))提供补充诊断和 向传统美国提供预后信息。这项研究的目标是将新工具Luama翻译为 用于评估乳腺肿块的临床工具。这项技术基于新的处理和量化 使用高帧频超声成像显示和量化微血管形态的程序。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 微血管系统的图像。我们计划解决乳腺癌的两个方面：识别恶性 应用3D成像系统评估肿块和术前化疗反应的准确性 微血管形态的评估。该项目包括两个具体目标：(1)确定诊断 Luama在一组可疑乳腺肿块的活检前患者中的表现与Luama相关 结果以病理为金标准。(2)评估和预测手术前的反应 使用Luama对乳腺癌患者进行化疗，并将结果与MRI进行对照。这 该提案是该领域几位专家合作的结果，并受益于世界级的 梅奥诊所的临床研究和设施。这项研究的成功完成将为 乳腺癌患者临床应用的新技术。Luama是一种非侵入性的、低成本、易于使用的 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和 可广泛应用于各种乳房患者。因此，这项研究有可能提供 在乳腺癌诊断和减少不必要的活检以及评估方面产生重大影响 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.