Contrast Ultrasound Detection of Sentinel Lymph Nodes in Breast Cancer Patients

描述（由申请人提供）：目前在给予放射性同位素和/或染料后进行术中淋巴标测，以定位前哨淋巴结（SLN）和分期乳腺癌患者。然而，这些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，蓝色染料可引起过敏反应，这些技术都不能提供准确的淋巴解剖结构的非侵入性描述。高达25%的患者会出现水肿等并发症。我们的小组已经证明，对比增强超声成像（CEUS）后，皮下注射组织特异性超声造影剂，可用于非侵入性映射淋巴引流和定位SLN（所谓的“淋巴超声”）。我们的NIH资助的研究使用了具有自然发生的黑色素瘤的猪模型，已经证实CEUS上级放射性同位素成像检测，几乎多20%的SLN。该项目的基本假设是，CEUS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，与同位素绘图相比，淋巴超声检查将改善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探索研究，以确定组织特异性造影剂Sonazoid（GE Healthcare，奥斯陆，挪威）用于人体淋巴应用的最佳剂量以及安全性和耐受性。然后，一项临床试验的淋巴超声检查将比较SLN的识别，在90例乳腺癌患者的手术同位素映射。一个国家的最先进的超声扫描仪与对比特异性成像能力将被用来定位淋巴引流乳腺癌后，皮下注射Sonazoid。将使用McNemar检验相关比例，以及使用单侧t检验和Wilcoxon非参数调整（假设正态分布），以染料引导手术作为SLN检测的参考标准，比较两种成像模式（CEUS和同位素标测）识别的SLN数量和位置。总之，本研究旨在确定90例乳腺癌患者中淋巴超声检查用于非侵入性SLN标测的临床潜力，并比较CEUS与同位素标测的使用。

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.