Contrast Ultrasound Detection of Sentinel Lymph Nodes in Breast Cancer Patients

描述（由申请人提供）：术中淋巴管造影定位前哨淋巴结（sln）并对乳腺癌患者进行分期目前是在给予放射性同位素和/或染料后进行的。然而，每种方法都有潜在的局限性，可能会影响sln的检测和疾病分期的准确性。此外，同位素成像需要电离辐射，蓝色染料可能引起过敏反应，这些技术都不能提供准确的无创淋巴解剖描述。高达25%的患者会出现淋巴水肿等并发症。我们的研究小组已经证明，皮下注射组织特异性超声造影剂后，对比增强超声成像（CEUS）可用于无创淋巴引流图和sln定位（即所谓的“淋巴超声”）。我们NIH资助的研究使用自然发生黑色素瘤的猪模型证实，超声造影优于放射性同位素成像检测近20%的sln。本项目的基本假设是超声造影可用于绘制乳腺恶性肿瘤的淋巴引流图并定位乳腺癌患者的sln，与同位素作图相比，淋巴超声可提高sln的检测，从而改善疾病分期。最初，将在12名健康女性志愿者中进行剂量研究，以确定组织特异性造影剂Sonazoid （GE Healthcare, Oslo, Norway）用于人体淋巴应用的最佳剂量、安全性和耐受性。然后，在90例乳腺癌患者的手术过程中，淋巴超声将SLN识别与同位素作图进行比较。具有对比特异成像能力的最先进的超声扫描仪将用于皮下注射索那唑后乳腺癌淋巴引流的定位。通过两种成像方式（超声造影和同位素成像）识别的SLN的数量和位置将使用McNemar的相关比例检验，以及使用带有Wilcoxon非参数调整（假设呈正态分布）的单侧t检验，并将染料引导手术作为SLN检测的参考标准。总之，本研究旨在确定90例乳腺癌患者淋巴超声无创SLN定位的临床潜力，并比较超声造影与同位素定位的使用。

DESCRIPTION (provided by applicant): Intraoperative lymphatic mapping to localize sentinel lymph nodes (SLNs) and stage breast cancer patients is currently performed after administration of radioisotopes and / or dye. However, each of these methods has potential limitations that can impact the detection of SLNs and the accuracy of disease staging. Furthermore, isotope imaging requires ionizing radiation, blue dye can cause anaphylactic reactions and neither of these techniques provides an accurate noninvasive depiction of lymphatic anatomy. Up to 25% of patients experience complications such as lymphedema. Our group has demonstrated that contrast-enhanced ultrasound imaging (CEUS) after subdermal administration of a tissue-specific ultrasound contrast agent, can be used to noninvasively map lymphatic drainage and localize SLNs (so called "lymphosonography"). Our NIH funded investigations using a swine model with naturally occurring melanomas have confirmed that CEUS is superior to radioisotope imaging detection almost 20 % more SLNs. The fundamental hypothesis of this project is that CEUS can be used to map lymphatic drainage from breast malignancies and localize SLNs in breast cancer patients and that lymphosonography will improve the detection of SLNs compared to isotope mapping leading to improved disease staging. Initially, a dose-finding study will be performed in 12 healthy female volunteers to determine the optimal dose as well as the safety and tolerability of the tissue-specific, contrast agent Sonazoid (GE Healthcare, Oslo, Norway) for human lymphatic applications. Then a clinical trial of lymphosonography will compare SLN identification to that of isotope mapping during surgery of 90 breast cancer patients. A state-of- the-art ultrasound scanner with contrast-specific imaging capabilities will be used to localize lymphatic drainage from breast cancers after subdermal administration of Sonazoid. The number and locations of the SLNs identified by the two imaging modalities (CEUS and isotope mapping) will be compared using McNemar's test for correlated proportions as well as using a one-sided t-test with a Wilcoxon non-parametric adjustment (assuming a normal distribution) with dye-guided surgery as the reference standard for SLN detection. In summary, this study aims to determine the clinical potential of lymphosonography for noninvasive SLN mapping in 90 breast cancer patients and compare the use of CEUS to isotope mapping.