Advances in fluorescent-image guided surgery
Review Articles on Innovations & Technology in Surgery

Advances in fluorescent-image guided surgery

Mark J. Landau, Daniel J. Gould, Ketan M. Patel

Division of Plastic and Reconstructive Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA

Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Ketan M. Patel, MD. Division of Plastic & Reconstructive Surgery, Keck Medical Center of USC, 1510 San Pablo St., Suite 415, Los Angeles, CA 90033, USA. Email:

Abstract: Fluorescence imaging is increasingly gaining intraoperative applications. Here, we highlight a few recent advances in the surgical use of fluorescent probes.

Keywords: Fluorescent probes; lymphedema; robotic surgical procedures; staining and labeling; surgery; tumor imaging

Submitted Jul 21, 2016. Accepted for publication Sep 21, 2016.

doi: 10.21037/atm.2016.10.70


The first use of fluorescent imaging in surgery dates to 1948 when surgeons noticed fluorescein concentration increased in malignant tissue and used this property to identify and localize intracranial neoplasms during neurosurgery (1). Since then, additional fluorescent agents have been used for a variety of surgical applications. Clinically, fluorescent agents can be used to establish positive margins with high resolution, map lymph nodes, detect residual disease, predict metastatic potential, and assist in drug delivery (2-8). Intraoperative fluorescence imaging offers the benefits of high contrast and sensitivity, low cost, ease of use, safety, and visualization of cells and tissues both in vitro and in vivo (9,10). Near-infrared contrast agents, such as the widely used indocyanine green (ICG), allow surgeons to visualize fluorescence wavelengths otherwise invisible to the naked eye while permitting deeper tissue penetration and enhanced contrast against autofluorescence (11,12). For the purpose of surgical oncology, an ideal probe provides the contrast required for resection of an entire tumor or affected lymph node while sparing healthy tissue (13). Therefore, a current challenge is to design probes with high selectivity for tumors, clear visualization, and minimal toxicity (14). Other applications of intraoperative fluorescent imaging, such as lymphatic imaging and angiography, also benefit from the development of new probes (10,12). An additional technical challenge remains in integrating new probes with surgical technology both existing and in development. We discuss three currently evolving uses of fluorescent probes in surgery: biochemically activatable “smart” probes, fluorescent imaging of the lymphatic system, and fluorescence-assisted robotic surgery. We also discuss new imaging modalities designed to improve detection of cancer.

Activatable fluorescent probes

Activatable fluorescent probes (“smart” probes) target tumor cells by taking advantage of the physiologic differences between cancerous and normal cells, thus enhancing tumor margin detection (15). These probes remain quenched until they are selectively activated into fluorescent molecules by tumor cells. Several strategies for this method of detection have been developed. One of the earliest examples of the use of these activatable fluorescent probes in vivo exploited the fact that proteolytic enzymes are of a higher concentration in tumors (16,17). The delivered agents, consisting of a fluorophore attached to a peptide, are cleaved by proteases to release a fluorescent molecule (16). This strategy has been applied to design activatable cell-penetrating peptides (ACPP) labeled with a Cy5 fluorophore and conjugated to a macromolecular dendrimer carrier, which reduces nonspecific uptake by skin, cartilage, and kidney (18-21). Tumor surgery in mice guided by these conjugated ACPPs resulted in fewer residual cancer cells in a variety of cancer models (20,21). Owing to their selective uptake into cancer cells, ACPPs have also been employed to deliver anti-neoplastic agents such as monomethyl auristatin E specifically to tumors (22-24). Recently, ratiometric ACPPs have been adapted to identify quantifiably measure both primary tumors and metastases, providing detailed information about cancer invasion (18,25-27).

Probes have also been developed to simultaneously target matrix metalloproteinase (MMP) with an activatable fluorescent probe and human epidermal growth factor receptor 2 (HER2) with an “always-on” probe (15). Targeting these two important biomarkers, which are commonly overexpressed in breast cancer, has the potential to improve the detection of tumor margins and intraoperatively provide information regarding the molecular characteristics of the tumor (15,28). Another example of simultaneous targeting involves an activatable fluorescent peptide targeting MMP-2, a protease with increased activities in many cancers, and integrin αvβ3, involved in the activation of MMP-2 (29-31). This molecule improved the fluorescent signal over MMP targeting alone and revealed a potential new strategy for the delivery of chemotherapeutic agents (29).

Several protease-activated fluorescent probes for topical administration have been synthesized (32,33). These probes can be sprayed onto tissue surfaces that are suspected of harboring tumors and require a lower dose than systemic administration (32,34). Human clinical studies of these probes revealed that on-site topical administration of aspirated specimens provided rapid visualization and diagnosis of pancreatic tumors (35). Work with “always on” fluorescent molecules has demonstrated that probes can also be topically applied directly to esophageal neoplasia in patients (34). These probes, which bind specifically to high-grade dysplasia and esophageal adenocarcinoma in Barrett’s esophageus, were safe and effective for localizing disease (34). These studies demonstrate another potential avenue for the delivery of smart probes.

Clinical trials have recently begun using LUM015, a protease-activated fluorescent molecule, constituting the first in-human phase 1 clinical trial of this type of imaging probe (36). The activation of LUM015 relies on cathepsin proteases, enzymes commonly overexpressed by tumors (37). LUM015 is optically inactive under normal conditions, but upon proteolytic cleavage by specific cathepsins, a covalently attached quencher molecule is released and fluorescence signal greatly intensifies (36). LUM015 was injected intravenously into 15 patients with either invasive ductal carcinoma or soft tissue sarcoma and was well tolerated with no adverse pharmacological activity (36). Tumors were surgically removed and examined ex vivo by fluorescent imaging (36,38). Six hours after injection, fluorescence signal in tumors was significantly higher than in adipose tissue or muscle, demonstrating the tumor-selective biodistribution and activation of LUM015 (36). These findings helped validate the use of LUM015 for intraoperative imaging as a means to intraoperatively define tumor margins, detect residual cancer cells, and reduce the rates of reexcision. Pharmacokinetics were similar between humans and mice, an encouraging finding that could increase the likelihood of additional activatable probes being translated to use in humans (36,39).

An additional strategy that does not rely on protease catalysis for activation instead uses a self-assembling polymer micelle conjugated to anti-HER2 antibodies with fluorescent probes encapsulated inside (40). These fluorescent probes become activated upon degradation of the micelle after its uptake into HER2-positive tumors, validating their potential use in visualizing and classifying tumors (40). Another probe design that relies on the unique surface environment of cancer cells takes advantage of the cell surface glycoprotein fibroblast activation protein-alpha to activate a fluorescence signal (41). Novel activatable probes targeting additional physiologic characteristics of cancer cells, such as thiol concentration, decreased pH, surface lectins, and antibody binding, are also currently in development (8,42-46). Translating these activatable probes into clinical studies could significantly increase the number and quality of intraoperative imaging tools available during cancer excision.

Endogenously synthesized fluorescent porphyrins have been used in the clinic to guide malignant glioma resection (47-50). Their use has allowed physicians to achieve a significantly higher rate of complete resections compared to surgeries done without the use of fluorescent visualization (47-51). Though not considered an activatable probe in the traditional sense, fluorescent porphyrin synthesis is stimulated in cancerous tissue by 5-aminolevulinic acid, a natural biochemical precursor of hemoglobin that is orally administered prior to surgery (49). This biological pathway further exemplifies the potential to exploit differences in cancer metabolism in designing selective probes with higher diagnostic accuracy and increased signal, two important challenges that remain in the implementation of fluorescent agents in surgery (52).

As new cancer targets are identified, fluorescent probes can be designed to bind them selectively. If these biomarkers are sufficiently specific for tumor cells, low systemic concentrations of fluorescent probes can achieve high concentrations within tumors and define tumor edges without the need for enzymatic activation. Such is the case for recently developed “always-on” probes that bind cancer biomarkers including urokinase plasminogen activator, folate receptor-α, carbonic anhydrase IX, and albumin degradation (53-57). However, combining the discovery of novel biomarkers with activatable fluorescent molecules has the potential to further increase selectivity and improve intraoperative tumor imaging.

Fluorescent imaging of the lymphatics

Fluorescent ICG has frequently been used as an alternative to dyes or radioactive gamma probes to guide sentinel lymph node biopsy (58-60). Fluorescent molecules offer the advantages of ease of use ease of use and low invasiveness compared to methods requiring exposure to radiation (58). ICG was effectively used as a surgical guide to accurately detect and remove axillary sentinel lymph nodes (58). Sentinel nodes were more likely to be identified by the fluorescence method than the blue dye method (60). Improved accuracy of sentinel lymph node biopsy allows the sparing of healthy nodes and potentially of the healthy portions of nodes partially invaded by metastasis, reducing the risk of post-surgical lymphedema. (59) The ability to precisely track lymphatic flow could also aid the design lymphatic-delivered therapies (59).

A recent study highlighted the use of a novel macrophage-specific fluorescent probe for intraoperative lymph node staging (61). Discovered via a high-throughput screen, this probe selectively binds monocytes and macrophages, the latter of which are a main component of lymph nodes (61). A deficient fluorescent signal caused by the replacement of macrophages by disseminated tumor cells could therefore diagnose the precise location of a nodal metastasis (61). Because of its unique binding property, this probe could be used not only to detect metastases in vivo but also to track local inflammation and adenopathy (61). Such studies lay the foundation for in vivo imaging technology that could eliminate unnecessary lymph node biopsies or dissections, reducing the postoperative complications of cancer therapies.

Some studies have demonstrated the potential use of multicolor quantum dots, each with a sharply defined emission spectrum, to simultaneously map lymphatic flow from multiple lymphatic basins (62-64). Fluorescent mapping of lymph flow from different regions can provide insight into drainage mechanisms and help surgical planning, reducing the incidence of postoperative lymphedema. Additionally, quantum dots offer the advantages of selective localization to and accumulation in axillary lymph nodes (65).

Beyond identifying sentinel lymph nodes intraoperatively, fluorescent molecules have also been used to examine secondary lymphedema as a complication following lymph node dissection. Preoperatively, ICG fluorescence can be used to assess the functional severity of lymphedema of the extremities and can help stage and select patients for surgical treatment (66-73). Compared to lymphoscintigraphy (the alternative method of imaging lymphedema), ICG fluorescence lymphography is more accurate, less invasive, and of a lower cost, making it more suitable for routine evaluations (74-76). Fluorescence visualization can also be utilized in evaluating other causes of lymphedema, such as lipedema, Fabry’s disease, congenital Milroy lymphedema, lymphatic malformations, or lymphedema praecox (71,77,78). Fluorescence lymphography is an important tool for lymphedema evaluation partially due to the fact that, unlike lymphoscintigraphy, fluorescent imaging can discriminate the lymphatic vessel contractility responsible for lymph flow (78-80).

Fluorescence lymphography is useful in early stages and mild cases of lymphedema, which is important when considering that lymphedema progresses slowly and may appear long after cancer treatment (81,82). Visualizing a “splash pattern” of fluorescence after ICG injection indicates a very early stage of lymphedema, even if the limb is otherwise asymptomatic (83). This allows physicians to detect lymphedema even in a subclinical stage, allowing for a timelier diagnosis and treatment of lymphedema (83). Fluorescent visualization provides better insight into lymphatic function when assessing lymphatic function prior to, during, or after surgery (79). It also helps determine the suitability of a lymphaticovenular shunt operation, one of the surgical treatments for lymphedema (74). ICG fluorescence is used intraoperatively to identify active lymphatic channels during lymphaticovenular shunt operations (79,84-88). Fluorescence imaging allows for the prompt identification of the functional lymphatic vessels and helps predict postsurgical outcomes (66).

Recent cases have demonstrated the versatility of ICG fluorescent visualization in potentially guiding the treatment of a multitude lymphatic disorders. Fluorescent imaging of lymphatic flow has been used outside of the realm of cancer and lymphedema as a means of aiding therapy for chylothorax (89,90). Chylothorax results from leakage of lymph from the thoracic duct or its tributaries, causing chyle to accumulate within the pleural cavity (89,91). It is a rare but serious complication following heart surgery in children (89). In one case involving a pediatric patient with chylothorax, ICG fluorescence helped physicians visualize obstructed lymphatic drainage and guide the choice of surgical intervention (89). ICG fluorescence lymphography was also used intraoperatively in two adult patients with lymphatic injury following an esophagectomy (90,92). In one case of chylothorax, ICG fluorescent imaging was used to identify the precise site of a chyle fistula, allowing surgeons to suture it and prevent chyle leakage (90). In a case of chylorrhea, intraoperative fluorescence navigation aided in thoracic duct ligation, successfully stopping the chylorrhea (92). These studies demonstrate that fluorescent probes could feasibly be employed to increase the efficiency of chylothorax and chylorrhea treatment and to reveal the pathogenesis of these poorly understood conditions (89,90,92-94). As a whole, fluorescent visualization has the potential to significantly increase our understanding of the lymphatic system, guide surgical intervention, and manage therapies (95).

Fluorescence-assisted robotic surgery

Fluorescent imaging has been used in a wide variety of applications to help guide robotic-assisted surgeries. Robotic surgeries are ideal for several procedures because they are precise, minimally invasive, and capable of reducing blood loss and shortening postoperative stay (96). Fluorescence has been used intraoperatively in these surgeries to visualize vascular and lymphatic anatomy, evaluate tissue perfusion, map biliary anatomy, identify lesions, and image metabolic activity (96-103). Combining the minimally-invasive approach of robotic surgery with the accuracy and precision of fluorescence has the potential to improve safety and outcomes in a wide range of treatments, with several studies already highlighting the benefits.

The major current uses of fluorescence-assisted robotic surgeries are in gastroenterologic, urologic, and gynecologic surgeries. During robotic-assisted esophagectomy, ICG allowed surgeons to examine and preserve the right gastroepiploic vascular arcade (97). It often identified small vessels that would not have otherwise been visualized (97). In robot-assisted laparoscopic gastrectomy, fluorescence imaging was used to identify lymph nodes from different lymphatic basins, helping surgeons sample the lymph nodes and stage gastric cancer patients (104). Because ICG is metabolized mainly by hepatic parenchymal cells and secreted into the bile, it has been used to visualize the biliary tree during robotic cholecystectomy for gallstone disease (101,105,106). This application of fluorescent imaging is safe, effective, and particularly helpful with obese patients or in cases of acute cholecystitis, two cases that make the surgery more challenging (101,106). In one case, fluorescent imaging during robotic cholecystectomy helped avoid surgical injury by identifying an aberrant canaliculus, a structure that is otherwise difficult to detect (100).

When applied to robotic-assisted colorectal surgery intended to spare the sphincter of rectal cancer patients, fluorescent imaging was used to simultaneously map local lymph nodes and assess perfusion status (4). This served the dual benefit of demarcating lymph node edges and preventing anastomotic leak, the most significant complication following this surgery (4,107). To this point, causes of anastomotic leakage after rectal surgery is considered unpredictable, but the ability to precisely visualize complex and possibly abnormal vasculature has the potential to reduce rates of ischemic injury (107). Additional studies have confirmed the benefit of fluorescent imaging in robotic-assisted surgeries for colorectal cancer, guiding surgeons and allowing them to adjust their planned incisions (98,99,108). One group employed a novel combination of fluorescence visualization and augmented-reality three-dimensional imaging to guide robotic duodenopancreatectomy in a patient with an intraductal papillary mucinous neoplasm (109). This research emphasizes the role of technological breakthroughs in surgery, robotics, and computer science in improving patient care.

Fluorescence-guided robotic surgery has found a wide range of applications in urologic procedures (110). The first use of this technology in this field helped to both identify renal vasculature and differentiate tumors from normal parenchyma in laparoscopic nephrectomy for renal cortical tumors (102). Interestingly, later studies showed that malignant kidney tumors tended to be hypofluorescent while benign tumors ranged from isofluorescent to hyperfluorescent, validating that ICG can also help differentiate between different tumor types (103). In robotic nephrectomies where warm ischemia is induced by renal artery clamping, using fluorescent visualization as a visual aid helped reduce the overall time the kidney was ischemic (111). As seen with other surgeries, ICG alerted surgeons to abnormal vascular anatomy, helping them avoid unintended injuries that would be otherwise difficult to predict (112,113). This technology could help surgeons spare larger portions of the kidney in partial nephrectomy and reduce postoperative complications, blood loss, and metastasis (113,114). Similarly, ICG was used in robotic partial adrenalectomy to differentiate between adrenal mass and normal parenchyma, helping to spare as much of the adrenal gland as possible while completely excising the tumor (115,116). This was also performed on the basis that several types of neoplasms are hypofluorescent on ICG imaging compared to normal tissue (115,116). Preclinical studies are currently underway to validate the use of fluorescence in anatrophic nephrolithotomy to identify avascular renal planes, assisting the removal of staghorn calculi (117). Intraureteric injection of ICG was used to identify the ureter and locate ureteral strictures in robotic-assisted ureteral construction (118,119). One group used a novel technique of imaging near-infrared fluorescence without an injectable contrast agent during robotic-assisted laporoscopic surgery of the urinary tract (120). Instead, they imaged the near-infrared emission of white light from endoscopic instruments (120). They were able to precisely identify the extent of a ureteric stricture, bladder diverticula, and tumor locations (120).

In robotic radical prostatectomy, ICG was injected into the prostate to mark prostatic tissue and map potential sentinel lymph nodes (121). Because ICG is not prostate specific, new fluorescent tracers that achieve targeting via prostate-specific membrane antigen are being developed to enhance tissue contrast (122). Bladder cancer patients underwent an experimental technique in which ICG was injected both directly into the tumor and intravenously (123). This permitted tumor marking, sentinel lymph node detection, and mesenteric vasculature identification to be accomplished simultaneously (123).

In a recent study, Paley et al. combined fluorescent lymph node mapping with robotic hysterectomy in patients with endometrial cancer (124). They found that this technology can help accurately and safely avoid full lymphadenectomies in women with high grade metastatic tumors, thus preventing secondary complications such as lymphedema (124). Previous research has confirmed that combining robotic-assisted hysterectomies with fluorescent sentinel lymph node mapping outperformed colorimetric dyes (125-128). These studies and their successors have the potential to change the standard of care for endometrial cancer therapy, which as of yet does not have a consensus regarding the utility of sentinel lymph node mapping (124).

An interesting application of fluorescence in robotic surgery involved its use in identifying nervous tissue in patients undergoing a robotic thymectomy (129). After injecting ICG, physicians were able to identify the periocardiophrenic neurovascular bundle with an 80% success rate (129). This technology could reduce surgery time and the risk of accidental nerve injury. During robotic anatomic segmentectomy, a procedure used to treat early-stage lung cancer, ICG was used to demarcate boundaries of lung segments for surgical resection (130). ICG could also identify the parathyroid glands in a canine model, suggesting yet another potential use in visualizing specialized tissue (131). Although additional studies are needed to fully validate the utility of fluorescent imaging in robotic-assisted surgeries, a growing body of evidence indicates that coupling these technologies has the potential to further increase the efficacy and safety of these procedures.

In vivo microscopy and nanotechnology

For many years now, several groups have focused on using live microscopy for better detection of certain cancer types, including notably oral cancer (132). Autofluorescence microscopy helps to better delineate cancerous tissues from normal tissues and assists in oral mucosa, where that differentiation may be very difficult. At Rice University, one collaboration between bioengineering laboratories and surgical oncologist has helped to develop an FDA approved device which harnesses a multispectral digital microscope, or one capable of several different imaging modalities to help better define cancerous lesions. Richards-Kortum and colleagues ran clinical trials and demonstrated this type of imaging may help better direct surgical biopsy and definitive therapy (133). This is one example of how advanced microscopy and multimodal imaging has led to an intraoperative guidance of resection.

Other labs have focused on the use of quantum dots or gold nanoshells to help label tumors and to provide for cellular imaging with near infrared microscopy that can penetrate human tissues (134,135). These very small materials can be fine-tuned in order to fluoresce or to generate heat when excited in order to serve as fluorescent markers of cells and tissues or to target tissues for ablation. Groups have shown this technology to be useful even in in vivo single molecular imaging for sentinel node navigation; they specifically developed it for molecular targeting drug-delivery systems (136). These advances represent a paradigm shift in the way we think about operations and intraoperative imaging. Imagine a situation where the surgeons can see only affected nodes and lymphatic channels, where they can have cellular resolution for their surgical resections or for image guidance. In the future these technologies could be combined and cells could be labelled and then utilized as therapeutic and they could be monitored in vivo.


Fluorescence imaging technology is gaining several new surgical applications. At the same time, the technology itself is frequently being updated, with many new fluorescent probes and imaging strategies in development. However, several obstacles and limitations still exist that must be overcome for fluorescent imaging to gain even wider use than its current applications. One question that remains is whether the potential benefits of fluorescent imaging warrant the cost of adding it to a surgical field. For example, one study estimated the cost adding near-infrared fluorescence imaging to robotic partial nephrectomy to be approximately $100,000 and the cost of ICG per vial to be approximately $100 (137). Additionally, imaging agents must undergo the same FDA approval process as other pharmaceutical drugs, making it take approximately a decade and $150 million for a fluorescent probe to become available on the market (3). These probes, however, seem much less lucrative to develop as they are only administered around the time of surgery rather than prescribed to be taken frequently. More evidence confirming the reduction of postoperative complications could help validate the initial time and expense required.

Iodine is rapidly excreted by the body and has a low penetrative ability (3,96). This means that to achieve sufficient contrast it must be administered very close to the time of surgery or the dose must be increased (36). The presence of inflammation, fibrosis, or excess fat also makes visualizing ICG more difficult (96,138). Another limitation to the implementation of these fluorescent probes is their contraindications. For example, approximately 1% of the population is hypersensitive to iodine and cannot be given ICG (139). Another contraindication is elevated liver function tests (113). Alternative imaging molecules must be sought for these patients. Additionally, newer detection methods could improve imaging by quantitatively assessing and mapping fluorescence intensity instead of relying on qualitative evaluation.

Studies are underway to identify molecules capable of selectively targeting specific tissues, many of which could have a significant clinical impact. Recently developed fluorescently labeled peptides can specifically label degenerated nerve branches, which in the future could aid patients undergoing surgical nerve repair (140). Another fluorescent probe was capable of quantitatively evaluating traumatic brain injury (141). Though these probes have not yet been used in humans, combining them with existing imagining and surgical technology has the potential to increase the efficacy of future surgeries. A great deal of current research and clinical trials are examining the potential use of quantum dots as an alternative fluorescent marker (65,142-145). These molecules would overcome the obstacle of iodine allergy and can be easily modified to alter their biodistribution and fluorescence emission. They also allow quantitative detection, have a high fluorescence intensity, and have a long emission lifetime. As fluorescence imaging becomes more sophisticated and targeted, additional surgical applications will follow, benefiting both patients and physicians.




Conflicts of Interest: The authors have no conflicts of interest to declare.


  1. Moore GE, Peyton WT, et al. The clinical use of fluorescein in neurosurgery; the localization of brain tumors. J Neurosurg 1948;5:392-8. [Crossref] [PubMed]
  2. Chi C, Du Y, Ye J, et al. Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology. Theranostics 2014;4:1072-84. [Crossref] [PubMed]
  3. Hussain T, Nguyen QT. Molecular imaging for cancer diagnosis and surgery. Adv Drug Deliv Rev 2014;66:90-100. [Crossref] [PubMed]
  4. Kim JC, Lee JL, Yoon YS, et al. Utility of indocyanine-green fluorescent imaging during robot-assisted sphincter-saving surgery on rectal cancer patients. Int J Med Robot 2015. [Epub ahead of print]. [Crossref] [PubMed]
  5. Mérian J, Gravier J, Navarro F, et al. Fluorescent nanoprobes dedicated to in vivo imaging: from preclinical validations to clinical translation. Molecules 2012;17:5564-91. [Crossref] [PubMed]
  6. Orosco RK, Tsien RY, Nguyen QT. Fluorescence imaging in surgery. IEEE Rev Biomed Eng 2013;6:178-87. [Crossref] [PubMed]
  7. Frangioni JV. New technologies for human cancer imaging. J Clin Oncol 2008;26:4012-21. [Crossref] [PubMed]
  8. Feng T, Ai X, Ong H, et al. Dual-Responsive Carbon Dots for Tumor Extracellular Microenvironment Triggered Targeting and Enhanced Anticancer Drug Delivery. ACS Appl Mater Interfaces 2016;8:18732-40. [Crossref] [PubMed]
  9. Alander JT, Kaartinen I, Laakso A, et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging 2012;2012:940585.
  10. Xi L, Jiang H. Image-guided surgery using multimodality strategy and molecular probes. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016;8:46-60. [Crossref] [PubMed]
  11. Mondal SB, Gao S, Zhu N, et al. Real-time fluorescence image-guided oncologic surgery. Adv Cancer Res 2014;124:171-211. [Crossref] [PubMed]
  12. Nguyen QT, Tsien RY. Fluorescence-guided surgery with live molecular navigation--a new cutting edge. Nat Rev Cancer 2013;13:653-62. [Crossref] [PubMed]
  13. Te Velde EA, Veerman T, Subramaniam V, et al. The use of fluorescent dyes and probes in surgical oncology. Eur J Surg Oncol 2010;36:6-15. [Crossref] [PubMed]
  14. Kobayashi H, Ogawa M, Alford R, et al. New strategies for fluorescent probe design in medical diagnostic imaging. Chem Rev 2010;110:2620-40. [Crossref] [PubMed]
  15. Chi C, Zhang Q, Mao Y, et al. Increased precision of orthotopic and metastatic breast cancer surgery guided by matrix metalloproteinase-activatable near-infrared fluorescence probes. Sci Rep 2015;5:14197. [Crossref] [PubMed]
  16. Weissleder R, Tung CH, Mahmood U, et al. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999;17:375-8. [Crossref] [PubMed]
  17. Yu AE, Hewitt RE, Connor EW, et al. Matrix metalloproteinases. Novel targets for directed cancer therapy. Drugs Aging 1997;11:229-44. [Crossref] [PubMed]
  18. Orosco RK, Savariar EN, Weissbrod PA, et al. Molecular targeting of papillary thyroid carcinoma with fluorescently labeled ratiometric activatable cell penetrating peptides in a transgenic murine model. J Surg Oncol 2016;113:138-43. [Crossref] [PubMed]
  19. Olson ES, Jiang T, Aguilera TA, et al. Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proc Natl Acad Sci U S A 2010;107:4311-6. [Crossref] [PubMed]
  20. Olson ES, Aguilera TA, Jiang T, et al. In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. Integr Biol (Camb) 2009;1:382-93. [Crossref] [PubMed]
  21. Nguyen QT, Olson ES, Aguilera TA, et al. Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc Natl Acad Sci U S A 2010;107:4317-22. [Crossref] [PubMed]
  22. Buckel L, Savariar EN, Crisp JL, et al. Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery. Cancer Res 2015;75:1376-87. [Crossref] [PubMed]
  23. Aguilera TA, Olson ES, Timmers MM, et al. Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides. Integr Biol (Camb) 2009;1:371-81. [Crossref] [PubMed]
  24. Jiang T, Olson ES, Nguyen QT, et al. Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc Natl Acad Sci U S A 2004;101:17867-72. [Crossref] [PubMed]
  25. Savariar EN, Felsen CN, Nashi N, et al. Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cell-penetrating peptides. Cancer Res 2013;73:855-64. [Crossref] [PubMed]
  26. Metildi CA, Felsen CN, Savariar EN, et al. Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Ann Surg Oncol 2015;22:2082-7. [Crossref] [PubMed]
  27. Hussain T, Savariar EN, Diaz-Perez JA, et al. Surgical molecular navigation with ratiometric activatable cell penetrating peptide for intraoperative identification and resection of small salivary gland cancers. Head Neck 2016;38:715-23. [Crossref] [PubMed]
  28. Rao JS. Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer 2003;3:489-501. [Crossref] [PubMed]
  29. Crisp JL, Savariar EN, Glasgow HL, et al. Dual targeting of integrin alphavbeta3 and matrix metalloproteinase-2 for optical imaging of tumors and chemotherapeutic delivery. Mol Cancer Ther 2014;13:1514-25. [Crossref] [PubMed]
  30. Deryugina EI, Ratnikov B, Monosov E, et al. MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells. Exp Cell Res 2001;263:209-23. [Crossref] [PubMed]
  31. Overall CM, Kleifeld O. Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer 2006;6:227-39. [Crossref] [PubMed]
  32. Urano Y, Sakabe M, Kosaka N, et al. Rapid cancer detection by topically spraying a gamma-glutamyltranspeptidase-activated fluorescent probe. Sci Transl Med 2011;3:110ra119. [Crossref] [PubMed]
  33. Sato C, Abe S, Saito Y, et al. A pilot study of fluorescent imaging of colorectal tumors using a gamma-glutamyl-transpeptidase-activatable fluorescent probe. Digestion 2015;91:70-6. [Crossref] [PubMed]
  34. Sturm MB, Joshi BP, Lu S, et al. Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: first-in-human results. Sci Transl Med 2013;5:184ra61. [Crossref] [PubMed]
  35. Kawakubo K, Ohnishi S, Hatanaka Y, et al. Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided Fine Needle Aspiration: a Pilot Study. Mol Imaging Biol 2016;18:463-71. [Crossref] [PubMed]
  36. Whitley MJ, Cardona DM, Lazarides AL, et al. A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer. Sci Transl Med 2016;8:320ra4. [Crossref] [PubMed]
  37. Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer 2006;6:764-75. [Crossref] [PubMed]
  38. Mito JK, Ferrer JM, Brigman BE, et al. Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging. Cancer 2012;118:5320-30. [Crossref] [PubMed]
  39. Cuneo KC, Mito JK, Javid MP, et al. Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents. Int J Radiat Oncol Biol Phys 2013;86:136-42. [Crossref] [PubMed]
  40. Shimizu Y, Temma T, Hara I, et al. Micelle-based activatable probe for in vivo near-infrared optical imaging of cancer biomolecules. Nanomedicine 2014;10:187-95. [PubMed]
  41. Li J, Chen K, Liu H, et al. Activatable near-infrared fluorescent probe for in vivo imaging of fibroblast activation protein-alpha. Bioconjug Chem 2012;23:1704-11. [Crossref] [PubMed]
  42. Ang CY, Tan SY, Lu Y, et al. "Turn-on" fluorescence probe integrated polymer nanoparticles for sensing biological thiol molecules. Sci Rep 2014;4:7057. [Crossref] [PubMed]
  43. Urano Y, Asanuma D, Hama Y, et al. Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat Med 2009;15:104-9. [Crossref] [PubMed]
  44. Ogawa M, Kosaka N, Choyke PL, et al. In vivo molecular imaging of cancer with a quenching near-infrared fluorescent probe using conjugates of monoclonal antibodies and indocyanine green. Cancer Res 2009;69:1268-72. [Crossref] [PubMed]
  45. Hama Y, Urano Y, Koyama Y, et al. A target cell-specific activatable fluorescence probe for in vivo molecular imaging of cancer based on a self-quenched avidin-rhodamine conjugate. Cancer Res 2007;67:2791-9. [Crossref] [PubMed]
  46. Lotan R, Raz A. Lectins in cancer cells. Ann N Y Acad Sci 1988;551:385-96; discussion 96-8. [Crossref] [PubMed]
  47. Guyotat J, Pallud J, Armoiry X, et al. 5-Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Surgery of High-Grade Gliomas: A Systematic Review. Adv Tech Stand Neurosurg 2016.61-90. [Crossref] [PubMed]
  48. Stummer W, Stocker S, Wagner S, et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 1998;42:518-25; discussion 25-6. [Crossref] [PubMed]
  49. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 2006;7:392-401. [Crossref] [PubMed]
  50. Stummer W, Novotny A, Stepp H, et al. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 2000;93:1003-13. [Crossref] [PubMed]
  51. Hadjipanayis CG, Widhalm G, Stummer W. What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence-Guided Surgery of Malignant Gliomas? Neurosurgery 2015;77:663-73. [Crossref] [PubMed]
  52. Valdés PA, Jacobs V, Harris BT, et al. Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery. J Neurosurg 2015;123:771-80. [Crossref] [PubMed]
  53. Yang L, Sajja HK, Cao Z, et al. uPAR-targeted optical imaging contrasts as theranostic agents for tumor margin detection. Theranostics 2013;4:106-18. [Crossref] [PubMed]
  54. van Dam GM, Themelis G, Crane LM, et al. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-alpha targeting: first in-human results. Nat Med 2011;17:1315-9. [Crossref] [PubMed]
  55. van Brussel AS, Adams A, Vermeulen JF, et al. Molecular imaging with a fluorescent antibody targeting carbonic anhydrase IX can successfully detect hypoxic ductal carcinoma in situ of the breast. Breast Cancer Res Treat 2013;140:263-72. [Crossref] [PubMed]
  56. Kremer P, Fardanesh M, Ding R, et al. Intraoperative fluorescence staining of malignant brain tumors using 5-aminofluorescein-labeled albumin. Neurosurgery 2009;64:ons53-60; discussion ons60-1.
  57. Andersson C, Iresjo BM, Lundholm K. Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice. J Surg Res 1991;50:156-62. [Crossref] [PubMed]
  58. Aoyama K, Kamio T, Ohchi T, et al. Sentinel lymph node biopsy for breast cancer patients using fluorescence navigation with indocyanine green. World J Surg Oncol 2011;9:157. [Crossref] [PubMed]
  59. Lucarelli RT, Ogawa M, Kosaka N, et al. New approaches to lymphatic imaging. Lymphat Res Biol 2009;7:205-14. [Crossref] [PubMed]
  60. Sugie T, Sawada T, Tagaya N, et al. Comparison of the indocyanine green fluorescence and blue dye methods in detection of sentinel lymph nodes in early-stage breast cancer. Ann Surg Oncol 2013;20:2213-8. [Crossref] [PubMed]
  61. Yoo JS, Lee SC, Jow ZY, et al. A macrophage-specific fluorescent probe for intraoperative lymph node staging. Cancer Res 2014;74:44-55. [Crossref] [PubMed]
  62. Hama Y, Koyama Y, Urano Y, et al. Simultaneous two-color spectral fluorescence lymphangiography with near infrared quantum dots to map two lymphatic flows from the breast and the upper extremity. Breast Cancer Res Treat 2007;103:23-8. [Crossref] [PubMed]
  63. Kobayashi H, Hama Y, Koyama Y, et al. Simultaneous multicolor imaging of five different lymphatic basins using quantum dots. Nano Lett 2007;7:1711-6. [Crossref] [PubMed]
  64. Kosaka N, Ogawa M, Sato N, et al. In vivo real-time, multicolor, quantum dot lymphatic imaging. J Invest Dermatol 2009;129:2818-22. [Crossref] [PubMed]
  65. Robe A, Pic E, Lassalle HP, et al. Quantum dots in axillary lymph node mapping: biodistribution study in healthy mice. BMC Cancer 2008;8:111. [Crossref] [PubMed]
  66. Chang DW, Suami H, Skoracki R. A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema. Plast Reconstr Surg 2013;132:1305-14. [Crossref] [PubMed]
  67. Hara H, Mihara M, Seki Y, et al. Comparison of indocyanine green lymphographic findings with the conditions of collecting lymphatic vessels of limbs in patients with lymphedema. Plast Reconstr Surg 2013;132:1612-8. [PubMed]
  68. Keo HH, Husmann M, Groechenig E, et al. Diagnostic accuracy of fluorescence microlymphography for detecting limb lymphedema. Eur J Vasc Endovasc Surg 2015;49:474-9. [Crossref] [PubMed]
  69. Keo HH, Schilling M, Buchel R, et al. Sensitivity and specificity of fluorescence microlymphography for detecting lymphedema of the lower extremity. Vasc Med 2013;18:117-21. [Crossref] [PubMed]
  70. Yamamoto T, Yamamoto N, Yoshimatsu H, et al. Indocyanine green lymphography for evaluation of genital lymphedema in secondary lower extremity lymphedema patients. J Vasc Surg Venous Lymphat Disord 2013;1:400-405.e1. [Crossref] [PubMed]
  71. Yamamoto T, Yoshimatsu H, Narushima M, et al. Indocyanine Green Lymphography Findings in Primary Leg Lymphedema. Eur J Vasc Endovasc Surg 2015;49:95-102. [Crossref] [PubMed]
  72. Unno N, Inuzuka K, Suzuki M, et al. Preliminary experience with a novel fluorescence lymphography using indocyanine green in patients with secondary lymphedema. J Vasc Surg 2007;45:1016-21. [Crossref] [PubMed]
  73. Unno N, Nishiyama M, Suzuki M, et al. A novel method of measuring human lymphatic pumping using indocyanine green fluorescence lymphography. J Vasc Surg 2010;52:946-52. [Crossref] [PubMed]
  74. Akita S, Mitsukawa N, Kazama T, et al. Comparison of lymphoscintigraphy and indocyanine green lymphography for the diagnosis of extremity lymphoedema. J Plast Reconstr Aesthet Surg 2013;66:792-8. [Crossref] [PubMed]
  75. Akita S, Mitsukawa N, Rikihisa N, et al. Early diagnosis and risk factors for lymphedema following lymph node dissection for gynecologic cancer. Plast Reconstr Surg 2013;131:283-90. [Crossref] [PubMed]
  76. Mihara M, Hara H, Narushima M, et al. Indocyanine green lymphography is superior to lymphoscintigraphy in imaging diagnosis of secondary lymphedema of the lower limbs. J Vasc Surg Venous Lymphat Disord 2013;1:194-201. [Crossref] [PubMed]
  77. Bollinger A, Amann-Vesti BR. Fluorescence microlymphography: diagnostic potential in lymphedema and basis for the measurement of lymphatic pressure and flow velocity. Lymphology 2007;40:52-62. [PubMed]
  78. Rasmussen JC, Fife CE, Sevick-Muraca EM. Near-Infrared Fluorescence Lymphatic Imaging in Lymphangiomatosis. Lymphat Res Biol 2015;13:195-201. [Crossref] [PubMed]
  79. Marshall MV, Rasmussen JC, Tan IC, et al. Near-Infrared Fluorescence Imaging in Humans with Indocyanine Green: A Review and Update. Open Surg Oncol J 2010;2:12-25. [Crossref] [PubMed]
  80. Tan IC, Maus EA, Rasmussen JC, et al. Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared fluorescence imaging. Arch Phys Med Rehabil 2011;92:756-764.e1. [Crossref] [PubMed]
  81. Mihara M, Hayashi Y, Hara H, et al. High-accuracy diagnosis and regional classification of lymphedema using indocyanine green fluorescent lymphography after gynecologic cancer treatment. Ann Plast Surg 2014;72:204-8. [Crossref] [PubMed]
  82. Mihara M, Hara H, Araki J, et al. Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PLoS One 2012;7:e38182. [Crossref] [PubMed]
  83. Yamamoto T, Matsuda N, Doi K, et al. The earliest finding of indocyanine green lymphography in asymptomatic limbs of lower extremity lymphedema patients secondary to cancer treatment: the modified dermal backflow stage and concept of subclinical lymphedema. Plast Reconstr Surg 2011;128:314e-21e. [Crossref] [PubMed]
  84. Chowdhry M, Rozen WM, Griffiths M. Lymphatic mapping and preoperative imaging in the management of post-mastectomy lymphoedema. Gland surgery 2016;5:187-96. [PubMed]
  85. Mehrara BJ, Zampell JC, Suami H, et al. Surgical management of lymphedema: past, present, and future. Lymphat Res Biol 2011;9:159-67. [Crossref] [PubMed]
  86. Patel KM, Manrique O, Sosin M, et al. Lymphatic mapping and lymphedema surgery in the breast cancer patient. Gland surgery 2015;4:244-56. [PubMed]
  87. Suami H, Chang DW, Yamada K, et al. Use of indocyanine green fluorescent lymphography for evaluating dynamic lymphatic status. Plast Reconstr Surg 2011;127:74e-6e. [Crossref] [PubMed]
  88. Mihara M, Seki Y, Hara H, et al. Predictive lymphatic mapping: a method for mapping lymphatic channels in patients with advanced unilateral lymphedema using indocyanine green lymphography. Ann Plast Surg 2014;72:706-10. [Crossref] [PubMed]
  89. Tan IC, Balaguru D, Rasmussen JC, et al. Investigational lymphatic imaging at the bedside in a pediatric postoperative chylothorax patient. Pediatr Cardiol 2014;35:1295-300. [Crossref] [PubMed]
  90. Kamiya K, Unno N, Konno H. Intraoperative indocyanine green fluorescence lymphography, a novel imaging technique to detect a chyle fistula after an esophagectomy: report of a case. Surg Today 2009;39:421-4. [Crossref] [PubMed]
  91. Zuluaga MT. Chylothorax after surgery for congenital heart disease. Curr Opin Pediatr 2012;24:291-4. [Crossref] [PubMed]
  92. Matsutani T, Hirakata A, Nomura T, et al. Transabdominal approach for chylorrhea after esophagectomy by using fluorescence navigation with indocyanine green. Case Rep Surg 2014;2014:464017.
  93. Ashitate Y, Tanaka E, Stockdale A, et al. Near-infrared fluorescence imaging of thoracic duct anatomy and function in open surgery and video-assisted thoracic surgery. J Thorac Cardiovasc Surg 2011;142:31-8.e1-2.
  94. Daggett JD, Watt AW, Smith PD. Chyle leak following right axillary lymph node dissection: A case report and review of current literature. Int J Surg Case Rep 2016;20:68-73. [Crossref] [PubMed]
  95. Maus EA, Tan IC, Rasmussen JC, et al. Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema. Head Neck 2012;34:448-53. [Crossref] [PubMed]
  96. Daskalaki D, Aguilera F, Patton K, et al. Fluorescence in robotic surgery. J Surg Oncol 2015;112:250-6. [Crossref] [PubMed]
  97. Sarkaria IS, Bains MS, Finley DJ, et al. Intraoperative near-infrared fluorescence imaging as an adjunct to robotic-assisted minimally invasive esophagectomy. Innovations (Phila) 2014;9:391-3. [Crossref] [PubMed]
  98. Bae SU, Baek SJ, Hur H, et al. Intraoperative near infrared fluorescence imaging in robotic low anterior resection: three case reports. Yonsei Med J 2013;54:1066-9. [Crossref] [PubMed]
  99. Hellan M, Spinoglio G, Pigazzi A, et al. The influence of fluorescence imaging on the location of bowel transection during robotic left-sided colorectal surgery. Surg Endosc 2014;28:1695-702. [Crossref] [PubMed]
  100. Calatayud D, Milone L, Elli EF, et al. ICG-fluorescence identification of a small aberrant biliary canaliculus during robotic cholecystectomy. Liver Int 2012;32:602. [Crossref] [PubMed]
  101. Daskalaki D, Fernandes E, Wang X, et al. Indocyanine green (ICG) fluorescent cholangiography during robotic cholecystectomy: results of 184 consecutive cases in a single institution. Surg Innov 2014;21:615-21. [Crossref] [PubMed]
  102. Tobis S, Knopf J, Silvers C, et al. Near infrared fluorescence imaging with robotic assisted laparoscopic partial nephrectomy: initial clinical experience for renal cortical tumors. J Urol 2011;186:47-52. [Crossref] [PubMed]
  103. Tobis S, Knopf JK, Silvers C, et al. Robot-assisted and laparoscopic partial nephrectomy with near infrared fluorescence imaging. J Endourol 2012;26:797-802. [Crossref] [PubMed]
  104. Herrera-Almario G, Patane M, Sarkaria I, et al. Initial report of near-infrared fluorescence imaging as an intraoperative adjunct for lymph node harvesting during robot-assisted laparoscopic gastrectomy. J Surg Oncol 2016;113:768-70. [Crossref] [PubMed]
  105. Buchs NC, Hagen ME, Pugin F, et al. Intra-operative fluorescent cholangiography using indocyanin green during robotic single site cholecystectomy. Int J Med Robot 2012;8:436-40. [Crossref] [PubMed]
  106. Spinoglio G, Priora F, Bianchi PP, et al. Real-time near-infrared (NIR) fluorescent cholangiography in single-site robotic cholecystectomy (SSRC): a single-institutional prospective study. Surg Endosc 2013;27:2156-62. [Crossref] [PubMed]
  107. Jafari MD, Lee KH, Halabi WJ, et al. The use of indocyanine green fluorescence to assess anastomotic perfusion during robotic assisted laparoscopic rectal surgery. Surg Endosc 2013;27:3003-8. [Crossref] [PubMed]
  108. Ozben V, Cengiz TB, Bayraktar O, et al. Identification of mesenteric lymph nodes in robotic complete mesocolic excision by near-infrared fluorescence imaging. Tech Coloproctol 2016;20:195-6. [Crossref] [PubMed]
  109. Pessaux P, Diana M, Soler L, et al. Robotic duodenopancreatectomy assisted with augmented reality and real-time fluorescence guidance. Surg Endosc 2014;28:2493-8. [Crossref] [PubMed]
  110. Autorino R, Zargar H, White WM, et al. Current applications of near-infrared fluorescence imaging in robotic urologic surgery: a systematic review and critical analysis of the literature. Urology 2014;84:751-9. [Crossref] [PubMed]
  111. Krane LS, Manny TB, Hemal AK. Is near infrared fluorescence imaging using indocyanine green dye useful in robotic partial nephrectomy: a prospective comparative study of 94 patients. Urology 2012;80:110-6. [Crossref] [PubMed]
  112. Herz D, DaJusta D, Ching C, et al. Segmental arterial mapping during pediatric robot-assisted laparoscopic heminephrectomy: A descriptive series. J Pediatr Urol 2016;12:266.e1-6. [Crossref] [PubMed]
  113. Bjurlin MA, Gan M, McClintock TR, et al. Near-infrared fluorescence imaging: emerging applications in robotic upper urinary tract surgery. Eur Urol 2014;65:793-801. [Crossref] [PubMed]
  114. Borofsky MS, Gill IS, Hemal AK, et al. Near-infrared fluorescence imaging to facilitate super-selective arterial clamping during zero-ischaemia robotic partial nephrectomy. BJU Int 2013;111:604-10. [Crossref] [PubMed]
  115. Manny TB, Pompeo AS, Hemal AK. Robotic partial adrenalectomy using indocyanine green dye with near-infrared imaging: the initial clinical experience. Urology 2013;82:738-42. [Crossref] [PubMed]
  116. Colvin J, Zaidi N, Berber E. The utility of indocyanine green fluorescence imaging during robotic adrenalectomy. J Surg Oncol 2016;114:153-6. [Crossref] [PubMed]
  117. Sood A, Hemal AK, Assimos DG, et al. Robotic Anatrophic Nephrolithotomy Utilizing Near-infrared Fluorescence Image-guidance: Idea, Development, Exploration, Assessment, and Long-term Monitoring (IDEAL) Stage 0 Animal Model Study. Urology 2016;94:117-22. [Crossref] [PubMed]
  118. Lee Z, Moore B, Giusto L, et al. Use of indocyanine green during robot-assisted ureteral reconstructions. Eur Urol 2015;67:291-8. [Crossref] [PubMed]
  119. Lee Z, Simhan J, Parker DC, et al. Novel use of indocyanine green for intraoperative, real-time localization of ureteral stenosis during robot-assisted ureteroureterostomy. Urology 2013;82:729-33. [Crossref] [PubMed]
  120. Hockenberry MS, Smith ZL, Mucksavage P. A novel use of near-infrared fluorescence imaging during robotic surgery without contrast agents. J Endourol 2014;28:509-12. [Crossref] [PubMed]
  121. Manny TB, Patel M, Hemal AK. Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients. Eur Urol 2014;65:1162-8. [Crossref] [PubMed]
  122. Laydner H, Huang SS, Heston WD, et al. Robotic real-time near infrared targeted fluorescence imaging in a murine model of prostate cancer: a feasibility study. Urology 2013;81:451-6. [Crossref] [PubMed]
  123. Manny TB, Hemal AK. Fluorescence-enhanced robotic radical cystectomy using unconjugated indocyanine green for pelvic lymphangiography, tumor marking, and mesenteric angiography: the initial clinical experience. Urology 2014;83:824-9. [Crossref] [PubMed]
  124. Paley PJ, Veljovich DS, Press JZ, et al. A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging. Am J Obstet Gynecol 2016;215:117.e1-7. [Crossref] [PubMed]
  125. Holloway RW, Bravo RA, Rakowski JA, et al. Detection of sentinel lymph nodes in patients with endometrial cancer undergoing robotic-assisted staging: a comparison of colorimetric and fluorescence imaging. Gynecol Oncol 2012;126:25-9. [Crossref] [PubMed]
  126. Sinno AK, Fader AN, Roche KL, et al. A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer. Gynecol Oncol 2014;134:281-6. [Crossref] [PubMed]
  127. Rossi EC, Ivanova A, Boggess JF. Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: a feasibility study. Gynecol Oncol 2012;124:78-82. [Crossref] [PubMed]
  128. Rossi EC, Jackson A, Ivanova A, et al. Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection. Int J Gynecol Cancer 2013;23:1704-11. [Crossref] [PubMed]
  129. Wagner OJ, Louie BE, Vallieres E, et al. Near-infrared fluorescence imaging can help identify the contralateral phrenic nerve during robotic thymectomy. Ann Thorac Surg 2012;94:622-5. [Crossref] [PubMed]
  130. Pardolesi A, Veronesi G, Solli P, et al. Use of indocyanine green to facilitate intersegmental plane identification during robotic anatomic segmentectomy. J Thorac Cardiovasc Surg 2014;148:737-8. [Crossref] [PubMed]
  131. Suh YJ, Choi JY, Chai YJ, et al. Indocyanine green as a near-infrared fluorescent agent for identifying parathyroid glands during thyroid surgery in dogs. Surg Endosc 2015;29:2811-7. [Crossref] [PubMed]
  132. de Veld DC, Bakker Schut TC, Skurichina M, et al. Autofluorescence and Raman microspectroscopy of tissue sections of oral lesions. Lasers Med Sci 2005;19:203-9. [Crossref] [PubMed]
  133. Roblyer D, Richards-Kortum R, Sokolov K, et al. Multispectral optical imaging device for in vivo detection of oral neoplasia. Journal of biomedical optics 2008;13:024019. [Crossref] [PubMed]
  134. Gao X, Chung LW, Nie S. Quantum dots for in vivo molecular and cellular imaging. Methods Mol Biol 2007;374:135-45. [PubMed]
  135. Pu K, Shuhendler AJ, Valta MP, et al. Phosphorylcholine-coated semiconducting polymer nanoparticles as rapid and efficient labeling agents for in vivo cell tracking. Advanced healthcare materials 2014;3:1292-8. [Crossref] [PubMed]
  136. Takeda M, Tada H, Higuchi H, et al. In vivo single molecular imaging and sentinel node navigation by nanotechnology for molecular targeting drug-delivery systems and tailor-made medicine. Breast Cancer 2008;15:145-52. [Crossref] [PubMed]
  137. Angell JE, Khemees TA, Abaza R. Optimization of near infrared fluorescence tumor localization during robotic partial nephrectomy. J Urol 2013;190:1668-73. [Crossref] [PubMed]
  138. Eriksson AG, Montovano M, Beavis A, et al. Impact of Obesity on Sentinel Lymph Node Mapping in Patients with Newly Diagnosed Uterine Cancer Undergoing Robotic Surgery. Ann Surg Oncol 2016;23:2522-8. [Crossref] [PubMed]
  139. Pradubpongsa P, Dhana N, Jongjarearnprasert K, et al. Adverse reactions to iodinated contrast media: prevalence, risk factors and outcome-the results of a 3-year period. Asian Pac J Allergy Immunol 2013;31:299-306. [Crossref] [PubMed]
  140. Hussain T, Mastrodimos MB, Raju SC, et al. Fluorescently labeled peptide increases identification of degenerated facial nerve branches during surgery and improves functional outcome. PLoS One 2015;10:e0119600. [Crossref] [PubMed]
  141. Smith BA, Xie BW, van Beek ER, et al. Multicolor fluorescence imaging of traumatic brain injury in a cryolesion mouse model. ACS Chem Neurosci 2012;3:530-7. [Crossref] [PubMed]
  142. Fang M, Peng CW, Pang DW, et al. Quantum dots for cancer research: current status, remaining issues, and future perspectives. Cancer Biol Med 2012;9:151-63. [PubMed]
  143. Gonda K, Miyashita M, Higuchi H, et al. Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging. Sci Rep 2015;5:14322. [Crossref] [PubMed]
  144. Kamila S, McEwan C, Costley D, et al. Diagnostic and Therapeutic Applications of Quantum Dots in Nanomedicine. Top Curr Chem 2016;370:203-24. [Crossref] [PubMed]
  145. Radenkovic D, Kobayashi H, Remsey-Semmelweis E, et al. Quantum dot nanoparticle for optimization of breast cancer diagnostics and therapy in a clinical setting. Nanomedicine 2016;12:1581-92. [PubMed]
Cite this article as: Landau MJ, Gould DJ, Patel KM. Advances in fluorescent-image guided surgery. Ann Transl Med 2016;4(20):392. doi: 10.21037/atm.2016.10.70