| Part I MR/SERRS probe for intraoperative visualization and image-guided resection of head-and-neck orthotopic tumor xenograft in rabbitObjective: Head and neck squamous cell carcinoma(HNSCC)characterized by infiltrative peri-neural growth,occult satellite foci and its prognosis remains to be unsatisfactory.Accurate intraoperative determination of infiltrated extent is pivotal for precise tumor resection.Therefore,high-sensitive imaging guided therapy has been an urgent requirement for clinical management.Methods: We have developed a highly sensitive nanoparticle termed Au NS-Cy7-Gd-PEG,which features a nano star-shaped core,a Raman reporter molecule Cy7 and Gd served as magnetic resonance imaging agent.The rabbit animal model bearing VX2 tumor was established by inoculating tumor suspensions in the masseter muscle of rabbits to mimic HNSCC.Results: Rabbits were randomized into white light guided and Raman guided surgical resection.An intraoperative Raman guided surgical resection was performed 24 hour post administration of Au NS-Cy7-Gd-PEG.Characteristic double peaks 509 cm-1 and 541cm-1 were visualized in tumor tissue while not in normal surrounding tissue.Adjusted directions of the probe and variable angles were performed step-by-step to detect possible microscopic and satellite metastases in surrounding areas of solid tumor till SERRS signals below the threshold.Nearly coincident tumor boundaries were observed between H&E staining and Raman macroscopic imaging.TEM results verified that abundant accumulation of Au NS-Cy7-Gd-PEG in tumor tissue whereas not detectable in surrounding normal areas.Notably,satellite metastasis embedded in tumor bed can be recognized through similar double peaks whereas no detectable signals were observed in normal area or normal muscle tissue containing satellite metastasis.Compared to white light guided group,less residual rate post surgical resection was observed in Raman guided group(10% vs 70%,p=0.02).Meanwhile,a significant prolonged survival time than that in control group or in white light guided group was found in Raman guided group with median survival time of 78 day(P<0.0001).Conclusions: Overall,we developed a MR/SERRS probe as an applicable strategy for image-guided therapy in head and neck tumors.High sensitivity,tumor-specific and real-time delineation or differentiation of tumor tissues would lead to precise surgical resection of tumor and improve patient prognosis.Part II MR-SERRS imaging study in animal model of lymph node metastasis in head and neck squamous cell carcinomaObjective: Cervical lymph node metastasis is the most common metastasis of head and neck squamous cell carcinoma.The traditional imaging method is still not ideal for the diagnosis of lymph node metastasis.Taking advantage of the high sensitivity and real-time imaging characteristics of MR/SERRS multimodal imaging,we studied the feasibility of rapid intraoperative diagnosis of metastatic lymph nodes.Methods: We constructed an animal model of cervical lymph node metastasis of rabbit VX2 tumor to simulate the cervical lymph node metastasis of HNSCC and used MRI-SERSS dual-mode imaging to guide the resection of cervical lymph node metastasis.Results: Preoperative MRI plain scan showed that the metastatic lymph nodes were of isointensity or slightly hypointensity and the boundary was blurred.After contrast-enhanced scanning,the enhancement of lymph node margin was relatively obvious,and no obvious enhancement was found in most of the central region.The signal intensity of metastatic lymph nodes was significantly different in plain scan(0.91 ±0.07)and enhanced ones(1.08 ±0.08)(P < 0.001).After 24 hours of SERRS nanoprobe administration,the SERSS-guided surgery was performed,Raman signal intensity analysis showed significant difference between metastatic lymph nodes(138 ±39)and non-metastatic lymph nodes(370 ±38)(P < 0.001).Conclusions: The application of intraoperative MR/SERRS imaging may quickly determine the status of cervical lymph nodes,improve the accuracy of lymph node resection,reduce complications and improve the prognosis. |
