Dynamic Visualization of Lymphatic Channels and Sentinel Lymph Nodes Using Intradermal Microbubbles and Contrast-Enhanced Ultrasound in a Swine Model and Patients With Breast Cancer

Abstract

ArticleObjective. Sentinel lymph node (SLN) identification using intradermal microbubbles and contrast-enhanced ultrasound (CEUS) has been recently reported in swine models and patients with breast cancer. The objective of this study was to investigate the dynamics of intradermally administered microbubbles as they travel to draining SLNs in pigs. We also performed a detailed study of the passage of microbubbles through breast lymphatic channels in a small group of patients with breast cancer. Methods. Nine anesthetized healthy pigs were used for the study, and 5 female patients with primary breast cancer were recruited. Pigs received intradermal injections of a microbubble contrast agent in several territories to access lymphatic drainage to regional lymph nodes. Patients had periareolar intradermal injection of the microbubble contrast agent. Ultrasound examination was performed in the real-time contrast pulse sequencing mode with a commercial scanner. Results. Sentinel lymph nodes were identified rapidly (<1 minute) and consistently in pigs. Intradermal microbubble injection and CEUS were found to have perfect concordance with the Evans blue dye method in locating swine SLNs. In all 5 patients with breast cancer, the microbubble contrast agent entered breast lymphatic channels and traveled to draining ipsilateral axillary SLNs within 3 minutes. Conclusions. Intradermally injected microbubbles traverse readily though lymphatic channels in pigs and human breast tissue. The ability to rapidly identify SLNs in the diagnostic period would enable targeted biopsy and may facilitate preoperative axillary staging in patients with early breast cancer.

Percutaneous removal of sentinel lymph nodes in a swine model using a breast lesion excision system and contrast-enhanced ultrasound

“…Further experimental studies were able to reproduce these results [5,6]. Recently it has been demonstrated that intradermally injected microbubbles and contrast enhanced ultrasound (CEUS) accurately identify SLNs preoperatively in breast cancer patients [7,8].…”

Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound

“…5 Sonographic contrast agents are composed of a dispersion of phospholipid stabilised microbubbles containing sulphur hexafluoride gas with a mean diameter of 2.5 mm. 6 In patients with breast cancer, we have previously shown that pre-operatively injected microbubbles and CEUS correctly identified 89% of those SLN found intraoperatively using blue dye and radioisotope. 7 In this study, we aimed to validate the technique of contrast-enhanced ultrasound (CEUS) as a test to identify sentinel lymph node (SLN) metastases in a large group of pre-operative breast cancer patients who had a normal axillary grey-scale ultrasound.…”

Perinodal fibrosis developed after ultrasonography‐guided core‐needle biopsy of a contrast‐enhanced ultrasound‐detected sentinel axillary node interferes with subsequent surgical sentinel node dissection

“…In our study, we followed the rationale of guiding the CNB to the lymph node cortex, where early metastatic tumor deposits develop . However, the CEUS technique justifies and enables percutaneous CNB of small benign‐appearing lymph nodes with a very thin cortex . Limiting the 14‐gauge needle's trajectory to a thin cortex is not possible.…”

“…Such lymph nodes are more prone to substantial structural damage and disruption of the hilar blood flow after a 14‐gauge CNB, which may induce the development of perinodal fibrosis. On the other hand, it is unlikely that the contrast agent itself could cause perinodal fibrosis because microbubble destruction occurs within a short time frame . Moreover, there has been no report of clinical, sonographic, or pathologic evidence of fibrosis or scarring at the site of CEUS intradermal injection in previous CEUS + CNB studies …”