Intraoperative margin delineation of neuroblastoma based on terahertz real-time imaging spectroscopy

Background: Neuroblastoma is a highly malignant, systemic sympathetic nerve tumor. Traditional surgical approaches often involve extensive excision, which can lead to additional tissue damage, underscoring the need for accurate and real-time tumor margin delineation. In this study, we introduce the application of Terahertz Time-Domain Spectroscopy (THz-TDS) for tumor margin assessment and rapid pathological evaluation in neuroblastoma. Methods: SH-SY5Y cells were employed to establish a subcutaneous tumor-bearing model in nude mice. Using a THz-TDS system, we conducted in vivo imaging of tumor-bearing mice in time domain signal and frequency domain signal, and performed transmission-mode THz detection on hematoxylin and eosin (HE) stained neuroblastoma tissue sections. In THz imaging, superparamagnetic iron oxide (SPIO) was introduced as a contrast agent to enhance the imaging performance. Results: The results revealed a strong THz reflection signal at the tumor site in the tumor-bearing mice, with the THz imaging system clearly delineating the tumor region in agreement with pathological findings. Neuroblasotuma tissues exhibited higher THz absorption coefficients compared to normal tissues. THz spectroscopy provides an excellent imaging contrast ratio in 0.5–1.0 THz, which can be further improved with SPIO nanoparticle agent. Additionally, we observed a statistically significant difference of refractive index and absorption coefficient between the HE-stained tumor and healthy tissue sections ( P < 0.01) within the frequency range of 0.5–1.5 THz. Conclusion: This work shows that THz-based imaging technology is able to distinguish the neuroblastoma and normal tissues in time and frequency domain, which offers a great potential for in vivo applications of neuroblastoma treatment. As an advanced technique, novel THz applications could open new avenues for precise diagnosing intraoperative neuroblastoma margins.