Near-infrared Intraoperative Imaging of Thoracic Sympathetic Nerves: From Preclinical Study to Clinical Trial

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.

[1]  I. Gouldsborough,et al.  Anatomic Variation of Rami Communicantes in the Upper Thoracic Sympathetic Chain: A Human Cadaveric Study. , 2016, Annals of vascular surgery.

[2]  D. Baker,et al.  Treatment of Primary Craniofacial Hyperhidrosis: A Systematic Review , 2015, American Journal of Clinical Dermatology.

[3]  Y. Issa,et al.  Preoperative opioid use and the outcome of thoracoscopic splanchnicectomy in chronic pancreatitis: a systematic review , 2013, Surgical Endoscopy.

[4]  Thoracoscopic sympathectomy. , 1994, European journal of vascular surgery.

[5]  G. Landry.  Current medical and surgical management of Raynaud's syndrome. , 2013, Journal of vascular surgery.

[6]  S. Singhal,et al.  Quantification of tumor fluorescence during intraoperative optical cancer imaging , 2015, Scientific Reports.

[7]  Jun Wang,et al.  Thoracoscopic Indocyanine Green Near-Infrared Fluorescence for Thoracic Sympathetic Ganglions. , 2016, The Annals of thoracic surgery.

[8]  K. Smidfelt,et al.  Late results of endoscopic thoracic sympathectomy for hyperhidrosis and facial blushing , 2011, The British journal of surgery.

[9]  R. Cerfolio,et al.  The Society of Thoracic Surgeons expert consensus for the surgical treatment of hyperhidrosis. , 2011, The Annals of thoracic surgery.

[10]  H. Vinters,et al.  Sympathetic nerve fibers in human cervical and thoracic vagus nerves. , 2014, Heart rhythm.

[11]  F. Crea,et al.  Sympathectomy as a treatment for refractory coronary artery spasm. , 2012, International journal of cardiology.

[12]  A. Purushotham,et al.  Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review. , 2014, The Lancet. Oncology.

[13]  Beth Friedman,et al.  Fluorescent peptides highlight peripheral nerves during surgery in mice , 2011, Nature Biotechnology.

[14]  Hee-Jin Kim,et al.  Anatomic variations of the T2 nerve root (including the nerve of Kuntz) and their implications for sympathectomy. , 2002, The Journal of thoracic and cardiovascular surgery.

[15]  Tsui-Fen Yang,et al.  Fluorescence-assisted visualization of facial nerve during mastoidectomy: A novel technique for preventing iatrogenic facial paralysis. , 2015, Auris, nasus, larynx.

[16]  Takeaki Ishizawa,et al.  Real‐time identification of liver cancers by using indocyanine green fluorescent imaging , 2009, Cancer.

[17]  Cornelis J H van de Velde,et al.  Near‐infrared fluorescence‐guided resection of colorectal liver metastases , 2013, Cancer.

[18]  J. Schulte am Esch,et al.  Interventional management of intractable sympathetically mediated pain by computed tomography‐guided catheter implantation for block and neuroablation of the thoracic sympathetic chain: technical approach and review of 322 procedures , 2011, Anaesthesia.

[19]  Shuming Nie,et al.  Near-infrared fluorescent image-guided surgery for intracranial meningioma. , 2017, Journal of neurosurgery.

[20]  Ismail Gögenur,et al.  Indocyanine green fluorescence angiography for intraoperative assessment of gastrointestinal anastomotic perfusion: a systematic review of clinical trials , 2016, Langenbeck's Archives of Surgery.

[21]  Jie Tian,et al.  Mathematical method in optical molecular imaging , 2014, Science China Information Sciences.

[22]  John V. Frangioni,et al.  Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery , 2011, Molecular imaging.

[23]  Jinzuo Ye,et al.  Comparison between the indocyanine green fluorescence and blue dye methods for sentinel lymph node biopsy using novel fluorescence image-guided resection equipment in different types of hospitals. , 2016, Translational research : the journal of laboratory and clinical medicine.

[24]  Ollin G Venegas,et al.  Optimization of the enhanced permeability and retention effect for near-infrared imaging of solid tumors with indocyanine green. , 2015, American journal of nuclear medicine and molecular imaging.

[25]  Kirk P. Withrow,et al.  Characterizing the Utility and Limitations of Repurposing an Open-Field Optical Imaging Device for Fluorescence-Guided Surgery in Head and Neck Cancer Patients , 2017, The Journal of Nuclear Medicine.

[26]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[27]  O. Wagner,et al.  Near-infrared fluorescence imaging can help identify the contralateral phrenic nerve during robotic thymectomy. , 2012, The Annals of thoracic surgery.

[28]  T. Sakurai,et al.  Axillary reverse mapping using fluorescence imaging is useful for identifying the risk group of postoperative lymphedema in breast cancer patients undergoing sentinel node biopsies , 2013, Journal of surgical oncology.

[29]  P. Low,et al.  Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results , 2011, Nature Medicine.

[30]  J. Porcheron,et al.  Affinity of Indocyanine Green in the Detection of Colorectal Peritoneal Carcinomatosis , 2017, Surgical innovation.

[31]  A. Mahajan,et al.  Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up. , 2014, Heart rhythm.

[32]  Jie Tian,et al.  Development and application of the near-infrared and white-light thoracoscope system for minimally invasive lung cancer surgery , 2017, Journal of biomedical optics.

[33]  Dong Peng,et al.  Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity , 2015 .

[34]  Jun Wang,et al.  Applications of indocyanine green based near-infrared fluorescence imaging in thoracic surgery. , 2016, Journal of thoracic disease.

[35]  G. Thalmann,et al.  A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection. , 2016, European urology.

[36]  R. Tsien,et al.  Fluorescence-guided surgery with live molecular navigation — a new cutting edge , 2013, Nature Reviews Cancer.

[37]  P. Licht,et al.  Late results of endoscopic thoracic sympathectomy for hyperhidrosis and facial blushing (Br J Surg 2011; 98: 1719–1724) , 2012, The British journal of surgery.

[38]  H. Coveliers,et al.  Thoracic sympathectomy for upper extremity ischemia. , 2016, Minerva cardioangiologica.

[39]  H. Coveliers,et al.  Thoracic sympathectomy for digital ischemia: a summary of evidence. , 2011, Journal of vascular surgery.

[40]  Jinzuo Ye,et al.  Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology , 2014, Theranostics.

[41]  D. Larsimont,et al.  Fluorescence Imaging After Indocyanine Green Injection for Detection of Peritoneal Metastases in Patients Undergoing Cytoreductive Surgery for Peritoneal Carcinomatosis From Colorectal Cancer: A Pilot Study , 2016, Annals of surgery.

[42]  Michael J Ackerman,et al.  The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy. , 2013, European heart journal.

[43]  K. Smidfelt,et al.  Authors' reply: Late results of endoscopic thoracic sympathectomy for hyperhidrosis and facial blushing (Br J Surg 2011; 98: 1719–1724) , 2012 .

[44]  Sunil Singhal,et al.  Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery. , 2016, Neurosurgery.

[45]  Shuming Nie,et al.  Near-Infrared Intraoperative Molecular Imaging Can Locate Metastases to the Lung. , 2017, The Annals of thoracic surgery.

[46]  Sunil Singhal,et al.  The second window ICG technique demonstrates a broad plateau period for near infrared fluorescence tumor contrast in glioblastoma , 2017, PloS one.

[47]  Shuming Nie,et al.  Intraoperative near-infrared imaging can identify pulmonary nodules. , 2014, The Annals of thoracic surgery.

[48]  P. Licht,et al.  Thoracic sympathectomy: a review of current indications , 2016, Surgical Endoscopy.

[49]  Josephine,et al.  Binding properties of indocyanine green in human blood. , 1998, Investigative ophthalmology & visual science.