An Operational Near-Infrared Fluorescence Imaging System Prototype for Large Animal Surgery

Near-infrared (NIR) fluorescence imaging has the potential to revolutionize human cancer surgery by providing sensitive, specific, and real-time intraoperative visualization of normal and disease processes. We have previously introduced the concept of a low-cost, safe, and easy-to-use NIR fluorescence imaging system that permits the surgeon to “see” surgical anatomy and NIR fluorescence simultaneously, non-invasively, with high spatial resolution, in real-time, and without moving parts [Nakayama et al. Molecular Imaging 1, 365–377 (2002)]. In this study, we present an operational prototype designed specifically for use during large animal surgery. Such a system serves as a foundation for future clinical studies. We discuss technical considerations, and provide details of the implementation of subsystems related to excitation light, light collection, computer, and software. Using the prototype, and the clinically available NIR fluorophore indocyanine green, we demonstrate vascular imaging in 35 kg pigs. Cancer-specific applications of this imaging system include image-guided cancer resection with real-time assessment of surgical margins, image-guided sentinel lymph node mapping, intraoperative mapping of tumor and normal vasculature, image-guided avoidance of critical structures such as nerves, and intraoperative detection of occult metastases in the surgical field. Taken together, this study describes an optical imaging system engineered for eventual translation to the clinic.

[1]  J. Frangioni.  In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[2]  R. Elashoff,et al.  Prolonged Survival of Patients Receiving Active Immunotherapy With Canvaxin Therapeutic Polyvalent Vaccine After Complete Resection of Melanoma Metastatic to Regional Lymph Nodes , 2002, Annals of surgery.

[3]  T. Mihaljevic,et al.  Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping , 2004, Nature Biotechnology.

[4]  Woo Kyung Moon,et al.  A Receptor‐Targeted Near‐Infrared Fluorescence Probe for In Vivo Tumor Imaging , 2002, Chembiochem : a European journal of chemical biology.

[5]  John V Frangioni,et al.  Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging. , 2003, Molecular imaging.

[6]  Ralph Weissleder,et al.  A Novel Near‐Infrared Fluorescence Sensor for Detection of Thrombin Activation in Blood , 2002, Chembiochem : a European journal of chemical biology.

[7]  R. Weissleder,et al.  Near-infrared fluorescent imaging of tumor apoptosis. , 2003, Cancer research.

[8]  M M Haglund,et al.  Enhanced optical imaging of rat gliomas and tumor margins. , 1994, Neurosurgery.

[9]  W. Semmler,et al.  Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands , 2001, Nature Biotechnology.

[10]  B. Lowell,et al.  Quantitation of Brown Adipose Tissue Perfusion in Transgenic Mice Using Near-Infrared Fluorescence Imaging , 2003 .

[11]  S. Achilefu,et al.  Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging. , 2000, Investigative radiology.

[12]  R. Weissleder,et al.  Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging , 2002, European Radiology.

[13]  P. Lehoang,et al.  Schematic interpretation of indocyanine green angiography in posterior uveitis using a standard angiographic protocol. , 1998, Ophthalmology.

[14]  J. Frangioni,et al.  Functional Near-Infrared Imaging for Cardiac Surgery and Targeted Gene Therapy , 2002 .

[15]  B. H. Crawford.  The Scotopic Visibility Function , 1949 .

[16]  J. S. Reynolds,et al.  Imaging of Spontaneous Canine Mammary Tumors Using Fluorescent Contrast Agents , 1999, Photochemistry and photobiology.

[17]  Yong Taik Lim,et al.  Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging , 2003, Molecular imaging.

[18]  A. Zaheer,et al.  IRDye78 Conjugates for Near-Infrared Fluorescence Imaging , 2002 .

[19]  Y Lecarpentier,et al.  Detection of the fluorescence of GI vessels in rats using a CCD camera or a near-infrared video endoscope. , 1999, Gastrointestinal endoscopy.

[20]  D. Morton,et al.  Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Eva M Sevick-Muraca,et al.  Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents. , 2002, Current opinion in chemical biology.

[22]  G WALD,et al.  The sensitivity of the human eye to infra-red radiation. , 1947, Journal of the Optical Society of America.

[23]  John V Frangioni,et al.  Functional Near-Infrared Fluorescence Imaging for Cardiac Surgery and Targeted Gene Therapy , 2002, Molecular imaging.

[24]  M M Haglund,et al.  Enhanced optical imaging of human gliomas and tumor margins. , 1996, Neurosurgery.

[25]  C. Goodeve.  Relative Luminosity in the Extreme Red , 1936 .

[26]  Vasilis Ntziachristos,et al.  In Vivo Imaging of Proteolytic Activity in Atherosclerosis , 2002, Circulation.

[27]  Ralph Weissleder,et al.  Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice. , 2002, Gastroenterology.

[28]  J. Still,et al.  Diagnosis of burn depth using laser-induced indocyanine green fluorescence: a preliminary clinical trial. , 2001, Burns : journal of the International Society for Burn Injuries.

[29]  Robert E. Lenkinski,et al.  In vivo near-infrared fluorescence imaging of osteoblastic activity , 2001, Nature Biotechnology.

[30]  T. Lamb,et al.  Photoreceptor spectral sensitivities: Common shape in the long-wavelength region , 1995, Vision Research.

[31]  Robert Folberg,et al.  Complex microcirculation patterns detected by confocal indocyanine green angiography predict time to growth of small choroidal melanocytic tumors: MuSIC Report II. , 2002, Ophthalmology.

[32]  D. Taggart,et al.  Preliminary experience with a novel intraoperative fluorescence imaging technique to evaluate the patency of bypass grafts in total arterial revascularization. , 2003, The Annals of thoracic surgery.

[33]  F L Lee,et al.  Indocyanine green angiography of central serous chorioretinopathy. , 1997, Zhonghua yi xue za zhi = Chinese medical journal; Free China ed.

[34]  Ralph Weissleder,et al.  Pan and sentinel lymph node visualization using a near-infrared fluorescent probe. , 2003, Molecular imaging.

[35]  W. Ye,et al.  Humoral immune response to a therapeutic polyvalent cancer vaccine after complete resection of thick primary melanoma and sentinel lymphadenectomy. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.