Basic research on photoacoustic sensing and imaging system for detecting sentinel lymph node in breast cancer

Abstract

Background and purpose: Sentinel lymph node biopsy (SLNB) is a standard staging technique for patients with clinical lymph nodes (LNs) negative early breast cancer. Blue staining combined with radionuclide method as the standard method of SLNB still has certain limitations. In this study, a new fluorescent targeted tracer indocyanine green-rituximab (ICG-RIT) was applied, and a handheld photoacoustic signal sensing (PASS) system and a handheld photoacoustic imaging (PAI) system were built to explore the tissue penetration depth of LNs enriched with ICG-RIT, and to study the feasibility of the new system locating LNs. Methods: In order to study the tissue penetration ability of ICG-RIT and localization ability of PASS and PAI, three experiments were designed. For the phantom experiment, the PASS was used to detect the ICG-RIT dyed gelatin phantom which was covered with chicken breast tissue to simulate LNs in vivo. For the human tissue experiment, after ICG-RIT was injected into the breast before operation, the LNs enriched with ICG-RIT were excised during the surgery and detected by the fluorescence imaging system and gamma probe detection system. The axillary LNs were covered with the axillary fat and detected by PASS, PAI and ultrasound imaging in sequence to compare the performance. For the rat lymph drainage model experiment, ICG-RIT was subcutaneously injected into the hind paw pad of SD rats to compare the PASS and PAI detection differences between popliteal LNs and iliac LNs. Results: The results of phantom experiment showed that ICG-RIT phantom under PASS detection showed the characteristic single-peak signal, and the signal amplitude was inversely proportional to the tissue depth, and the maximum detection depth was 52.42 mm on average. The human tissue experiment results showed that the maximum detection depth of ICG-RIT stained LNs under axillary fat detected by PASS was 32.72 mm, and the maximum detection depth of ICG-RIT stained phantom under 6.25% concentration of chicken breast tissue was 39.72 mm. The PAI detected ICG-RIT stained LNs in axillary fat up to 25 mm in depth. The results of SD rat model showed that ICG-RIT was collected by the popliteal LNs of SD rats, showing a monopolar curve on the PASS and a characteristic ‘hot spot’ on the PAI, and no obvious photoacoustic signal was found in iliac LNs. On the contrary, the methylene blue simultaneously stained popliteal LNs and iliac LNs. Conclusion: Taking advantage of the photoacoustic effect and targeting LNs characteristics of ICG-RIT, SLN can be accurately located by handheld PASS and handheld PAI with good penetration depth in tissue, showing potentials in clinical application. However, further clinical trial data are still needed to validate its clinical values.

Keywords

• |breast cancer|photoacoustic imaging|sentinel lymph node biopsy|new fluorescent targeted tracer