Sentinel Node Biopsy for the Head and Neck Using Contrast-Enhanced Ultrasonography Combined with Indocyanine Green Fluorescence in Animal Models: A Feasibility Study

Abstract

BackgroundSentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast-enhanced ultrasonography and indocyanine green fluorescence in animal models.MethodsThis was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically.ResultsSentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically.ConclusionsThe combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted.

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma

“…To review contrast-enhanced lymphosonography in OSCC, a systematic literature search was conducted, which led to retrieval of 107 PubMed indexed articles. A total of 6 studies were considered relevant (i.e., 2 clinical studies [ 34 , 35 ] and 4 large animal studies [ 82 , 83 , 84 , 85 ]). Cross-reference did not lead to identification of additional relevant articles.…”

“…Furthermore, none of the studies in humans or large animals found HEN enhancement [ 34 , 35 , 82 , 83 , 84 , 85 ]. It is possible that this is prevented by phagocytosis of microbubbles (which was histologically confirmed in animals for Sonazoid [ 85 ]) and the size of microbubbles compared to small-molecule dyes. Another advantage is the possibility to use lymphosonography preoperatively to improve lymph node selection for USgFNA.…”

“…The two clinical studies report a specific contrast imaging mode at a low mechanical index (MI), thus leaving the microbubbles intact [ 34 , 35 , 82 , 83 , 85 ]. Four animal studies performed lymphosonography in the head and neck region using Sonazoid, combined with either blue dye or ICG, in swine and rabbits without tumors [ 82 , 83 , 85 ] and with Definity in dogs with spontaneously arisen tumors [ 84 ]. The studies in swine added color flow Doppler at a high (microbubble destructing) mechanical index of 1.0 to confirm the presence of microbubbles [ 82 , 83 ].…”

A real‐time prediction model for post‐irradiation malignant cervical lymph nodes

“…In addition, a verification bias may exist because patients with benign cytopathologic results and follow‐up for at least 12 months were considered negative. Second, several novel US techniques, such as real‐time or shear wave elastography and contrast‐enhanced ultrasonography, were not assessed, and their adaptation may improve this prediction model in the future. Third, we did not compare that if there were differences in criteria between different head and cancers in this study.…”

Response Evaluation in Head and Neck Oncology: Definition and Prediction

“…The combination of contrast-enhanced ultrasound and fluorescence imaging for the intraoperative detection of sentinel lymph nodes is a new development in the field of visualization techniques [38] . Contrast-enhanced ultrasound alone could potentially detect radiation-induced changes in the carotid arteries at an early stage, offering modulation of the local radiation dose [28] .…”