The sympathetic nervous system controls and regulates the activities of the heart and other organs. Sympathetic nervous system dysfunction leads to disease. Therefore, intraoperative real-time imaging of thoracic sympathetic nerves (ITSN) would be of great clinical significance for diagnosis and therapy. The aim of this experimental study was to evaluate the feasibility and validity of intraoperative ITSN using indocyanine green (ICG).Methods: ITSN using ICG was performed on 10 rabbits to determine its feasibility. Animals were allocated to two groups. The rabbits in one group received the same dose of ICG, but were observed at different times. The rabbits in the other group were administered different doses of ICG, but were observed at the same time. Signal to background ratio (SBR) was measured in regions of interest in all rabbits. Furthermore, fifteen consecutive patients with pulmonary nodules were intravenously injected with ICG 24 h preoperatively and underwent near-infrared (NIR) fluorescence imaging (FI) thoracoscopic surgeries between July 2015 and June 2016. A novel self-developed NIR and white-light dual-channel thoracoscope system was used. SBRs of thoracic sympathetic nerves were calculated in all patients.Results: In the preclinical study, we were able to precisely recognize each rabbit's second (T2) to fifth (T5) thoracic ganglia on both sides of the spine using ITSN with ICG. In addition, we explored the relationship between SBR and the injection time of ICG and that between SBR and the dose of ICG. Using the novel dual-channel thoracoscope system, we were able to locate the ganglia from the stellate ganglion (SG) to the sixth thoracic ganglion (T6), as well as the chains between these ganglia in all patients with a high SBR value of 3.26 (standard deviation: 0.57). The pathological results confirmed our findings.Conclusion: We were able to use ICG FI to distinguish thoracic sympathetic nerves during NIR thoracoscopic surgery. The technique may replace the rib-oriented method as standard practice for mapping the thoracic sympathetic nerves.
Supra-maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM-specific fluorescence probe using IRDye800CW (peak absorption/ emission, 778/795 nm) and bombesin (BBN), which (IRDye800-BBN) targets the gastrin-releasing peptide receptor, and evaluated the image-guided resection efficiency, sensitivity, specificity, and survivability. Twenty-nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800-BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6-100%). Eighty-nine samples were harvested, including 70 fluorescence-positive and 19 fluorescencenegative samples. The sensitivity and specificity of IRDye800-BBN were 94.44% (95% CI, 85.65-98.21%) and 88.24% (95% CI, 62.25-97.94%), respectively. Twenty-five Kunshan He, Chongwei Chi, Deling Li, and Jingjing Zhang authors contributed equally to this work.
Although the combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy has improved survival rates in selected patients with peritoneal metastasis (PM), therapeutic efficiency remains a challenge due to low targeting specificity, poor tissue penetration of chemotherapy drugs, and incomplete tumor clearance. To overcome these drawbacks, novel gold nanoshells conjugated with indocyanine green (I‐GSNs) for image‐guided photothermal adjunctive CRS (iPTA‐CRS) are synthesized. The as‐prepared nanoparticles effectively accumulate both in subcutaneously transplanted and PM models. I‐GSN‐mediated near‐infrared imaging provides sufficient optical contrast for preoperative guidance and intraoperative resection with the accurate detection of visible/microtumor lesions (<3 mm). The strategy is significantly more effective for removing subcutaneously transplanted tumors, inhibiting PM nodules of the gastric tumor, and enhancing the survival rate (≈33%) than other treatments (0%) in the 60 d observation period. This novel iPTA‐CRS may benefit future clinical translations for gastric cancer patients with PM.
Bladder cancer (BC) is a common human malignancy. Conventional ultrasound and white light cystoscopy are often used for BC diagnosis and resection, but insufficient specificity results in a high BC recurrence rate. New strategy for the diagnosis and resection of BC are needed. In this study, we developed a highly specific peptide-based probe for BC photoacoustic imaging (PAI) diagnosis and near-infrared (NIR)-imaging-guided resection post-instillation. A BC-specific peptide (PLSWT7) was selected by in vivo phage display technology and labeled with IRDye800CW to synthesize a BC-specific dual-modality imaging (DMI) probe (PLSWT7-DMI). The feasibility of PLSWT7-DMI-based dual-modality PAI-NIR imaging was assessed in vitro, in mouse models, and ex vivo human bladders. An air-pouch BC (APBC) model suitable for probe instillation was established to evaluate the probe-based BC PAI diagnosis and NIR-imaging-guided resection. Human bladders were used to assess whether PLSWT7-DMI-based DMI strategy is a translatable approach for BC detection and resection. The probe exhibited excellent selectivity and specificity both in vitro and in vivo. Post-instillation of the probe, tumors <3 mm were detectable by PAI, and NIR-imaging-guided tumor resection decreased the BC recurrence rate by 90% and increased the survival in the mouse model. Additionally, ex vivo NIR imaging of human bladders indicated that PLSWT7-DMI-based imaging would potentially allowed precise resection of BC in clinical settings. This PLSWT7-DMI-based DMI strategy was a translatable approach for BC diagnosis and resection and could potentially lower the BC recurrence rate.
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