Improving diagnostic US for reduction of benign breast biopsies using US-guided Optical Tomography

标题：使用超声引导扩散光学成像提高乳腺活检的超声诊断特异性 断层扫描 摘要 在目前的临床实践中，虽然恶性和良性乳腺病变的特征已经很好地建立， 通过常规成像技术，恶性和良性病变的重叠表现， 促使放射科医生建议对大多数低风险和中等风险的乳腺病变进行活检。结果在 在美国，每年进行大约一百万次图像引导乳腺活检， 大多数病变产生良性结果。为改善这种情况所作的许多努力都没有成功。 本申请将探讨超声（US）引导的扩散光学断层扫描（DOT）的潜在影响， 在诊断环境中作为超声的辅助手段，目的是减少良性活检而不损害癌症 检测灵敏度US引导的DOT提供血红蛋白浓度值和分布， 绘制病变血管分布或血管生成图。最近，我们回顾性评估了288例患者， 我们的技术在表征低风险和中等风险乳腺病变方面的潜在临床影响， 如果在活检决策过程中使用了超声引导DOT技术，则需要进行活检。在这 患者队列中，总血红蛋白水平结合两名放射科医生的诊断， 96.6-100%的癌症检测和99- 100%的阴性预测值。使用保守阈值 总血红蛋白（tHb）数据来区分基于血管数量的病变，我们发现 的病变，将被称为活检平均下降约45%，同时保持高 检测灵敏度 我们的假设是：1）第一个假设是，测量的tHb值和分布可能是潜在的 用作放射科医生的辅助手段，以减少低风险良性病理性病变患者的不必要活检 第二个假设是，在减少不必要的良性活检的同时， 来自US引导的DOT的信息仍然保持捕获几乎所有恶性肿瘤的高灵敏度。在 本申请中，我们提出了三个目标：1）优化和验证一种新的非迭代成像 重建算法和新的统计方法，用于自动数据处理，稳健的数据选择， 近实时成像的目标是由医生进行现场诊断。这是向前迈出的重要一步， 该技术进入临床; 2）前瞻性评估连续性US引导DOT对传统DOT的影响 乳腺影像学检查对乳腺癌的准确诊断和减少良性活检的重要性。约300名患者 将在华盛顿大学放射学系招募，以验证早期回顾性结果; 以及3）进行统计分析以验证良性活检的减少，同时保持高灵敏度。 该项目的成功完成将有助于启动我们如何管理低风险良性模式的转变 在目前的临床实践中不损害癌症检测灵敏度的病变，并将减少医疗保健 不影响患者护理的成本。

Title: Improving diagnostic US specificity on breast biopsies using US-guided Diffuse Optical Tomography Abstract In current clinical practice, while the characteristics of malignant and benign breast lesions are well established by conventional imaging techniques, the overlapping appearances of malignant and benign lesions have prompted radiologists to recommend biopsy for most low and moderate risk breast lesions. As a result, in the United States, approximately one million image-guided breast biopsies are performed each year, with the majority of the lesions yielding benign results. Many attempts to improve this situation have not been successful. This application will explore the potential impact of Ultrasound (US)-guided diffuse optical tomography (DOT) as an adjunct to US in a diagnostic setting, with the goal of reducing benign biopsies without compromising cancer detection sensitivity. US-guided DOT provides hemoglobin concentration values and distributions which in turn map out lesion vascularity or angiogenesis. Recently, we retrospectively evaluated 288 patients to assess the potential clinical impact of our technique in characterizing low and moderate risk breast lesions, which might not need to be biopsied if the US-guided DOT technology were used in the biopsy decision making process. In this patient cohort, the total hemoglobin level combined with two radiologists’ diagnosis achieved high sensitivity of 96.6-100% on cancer detection and negative predictive value of 99-100%. Using a conservative threshold for the total hemoglobin (tHb) data to differentiate lesions based on the amount of vascularity, we found the number of lesions that would be referred to biopsy decreased by approximately 45% on average, while maintaining high detection sensitivity. Our hypotheses are: 1) The first hypothesis is that the measured tHb values and distribution can be potentially used as an adjunct for radiologists to reduce unnecessary biopsies in low risk patients with benign pathological results; and 2) The second hypothesis is that while reducing unnecessary benign biopsies, the addition of adjunct information from US-guided DOT still maintains a high sensitivity of capturing nearly all malignant tumors. In this application, we propose three aims: 1) Optimization and validation of a new non-iterative imaging reconstruction algorithm and new statistical methods for automated data processing, robust data selection, with the goal of near real-time imaging for onsite diagnosis by physicians. This is a significant step forward to bring this technology into clinics; 2) To prospectively assess the impact of adjunctive US-guided DOT to conventional breast imaging on accurate breast cancer diagnosis and reduction of benign biopsy. Approximate 300 patients will be recruited at the Radiology Department of Washington University to validate the early retrospective results; and 3) Perform statistical analysis to validate the reduction of benign biopsy while maintaining high sensitivity. The successful completion of the project will help initiate a paradigm shift in how we manage low risk benign lesions without compromising cancer detection sensitivity in current clinical practice and will reduce health care cost without compromising patient care.