Image-guided surgery of head and neck carcinoma in rabbit models by intra-operatively defining tumour-infiltrated margins and metastatic lymph nodes.
BACKGROUND
The infiltrative nature and lymphatic metastasis of head and neck squamous cell carcinoma (HNSCC) are the main reasons leading to its poor prognosis.


METHODS
A multimodal surface-enhanced resonance Raman spectroscopy (SERRS) and magnetic resonance (MR) nanoprobe, in which paramagnetic chelators and heptamethine cyanine-based Raman reporter molecules were functionalized on a gold nanostar (AuS) surface was developed. Preoperative MRI and intraoperative SERRS-guided surgery were performed on rabbits bearing head and neck VX2 tumours to determine feasibility of the MR/SERRS probe in defining tumour marginal infiltration and lymph nodes metastasis.


FINDINGS
Preoperative T1-weighted MRI (T1W-MRI) unambiguously delineated the orthotopic head and neck VX2 tumour xenograft and detected the metastatic lymph nodes in rabbit models after intravenous administration of the probe. With the assistance of a hand-held Raman detector, the probe not only intra-operatively demarcated invasive tumour margins but also successfully distinguished metastatic lymph nodes via a remarkable attenuated Raman signal. Importantly, the group of rabbits subjected to the SERRS-guided surgery exhibited prolonged median survival time (78 days) compared with that of the control group without surgical intervention (29 days) or the group treated with conventional white-light-guided surgery (42 days) (P < 0.0001).


INTERPRETATION
we developed a novel AuS-based multimodal MR/SERRS probe. The capability of this probe to identify both a tumour xenograft and metastatic lymph nodes preoperatively by MRI and intra-operatively by SERRS not only avoids the need for unnecessary resection of neurological structures but also provides a new opportunity to improve the surgical prognosis of head and neck carcinoma of infiltrative nature.