Optical Image-guided Surgery—Where Do We Stand?

Department of Otorhinolaryngology, Head & Neck Surgery, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging (Impact Factor: 2.77). 04/2011; 13(2):199-207. DOI: 10.1007/s11307-010-0373-2
Source: PubMed

ABSTRACT In cancer surgery, intra-operative assessment of the tumor-free margin, which is critical for the prognosis of the patient, relies on the visual appearance and palpation of the tumor. Optical imaging techniques provide real-time visualization of the tumor, warranting intra-operative image-guided surgery. Within this field, imaging in the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-to-background-ratio of contrast agents. In this article, we review the various techniques, contrast agents, and camera systems that are currently used for image-guided surgery. Furthermore, we provide an overview of the wide range of molecular contrast agents targeting specific hallmarks of cancer and we describe perspectives on its future use in cancer surgery.

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Available from: Clemens W G M Löwik, Sep 28, 2015
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    • "This design can be applied to develop a range of more sensitive and rapidly responsive NIR fluorescent probes not only for MMP activity, but also for other proteases 168. However, the major limitation for the clinical application of new NIR fluorescent agents is that each fluorophore-ligand conjugate must receive regulatory approval separately, which is costly and time consuming 174. "
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    ABSTRACT: Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.
    Theranostics 08/2014; 4(11):1072-1084. DOI:10.7150/thno.9899 · 8.02 Impact Factor
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    • "Although radiological approaches such as computed tomography (CT) and magnetic resonance imaging (MRI) have been of great help in characterizing malignancies within peritoneal cavity, they are not useful for intraoperative assessment. In contrast, fluorescence imaging has been shown to be successful in preclinical and clinical trials as an optical technique offering real-time images of surgical targets (peritoneal carcinomatosis and breast cancer) with adequate imaging resolution and high intraoperative sensitivity [4]–[8]. Coll and colleagues reported that intraoperative near-infrared (NIR) fluorescence image-guided surgery using a tumor-targeting peptide, RAFT-c(RGDfK)4-Alex Fluor 700 (IV route), in a TSA-pGL3-bearing mouse model of peritoneal adenocarcinoma could improve the quality of surgical debulking by doubling the number of detected tumor nodules and shortening operation time [5]. "
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    ABSTRACT: In a two-step strategy, an intraperitoneal (IP) injection of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles containing paclitaxel (PTX), cyclopamine (CYP), and gossypol (GSP) at 30, 30, and 30 mg/kg, respectively, debulked tumor tissues by 1.3-fold, based on loss of bioluminescence with <10% body weight change, and induced apoptosis in peritoneal tumors when used as neoadjuvant chemotherapy (NACT) in an ES-2-luc-bearing xenograft model for ovarian cancer. In a second step, a single intravenous (IV) injection of apoptosis-targeting GFNFRLKAGAKIRFGS-PEG-b-PCL micelles containing a near-infrared (NIR) fluorescence probe, DiR (1,1'-dioctadecyltetramethyl indotricarbocyanine iodide), resulted in increased peritoneal DiR accumulation in apoptosis-induced ES-2-luc tumor tissues (ex vivo) by 1.5-fold compared with DiR molecules delivered by methoxy PEG-b-PCL micelles (non-targeted) at 48 h after IV injection in a second step. As a result, a tandem of PEG-b-PCL micelles enabled high-resolution detection of ca. 1 mm diameter tumors, resulting in resection of approximately 90% of tumors, and a low peritoneal cancer index (PCI) of ca. 7. Thus, a tandem of PEG-b-PCL micelles used for NCAT and NIR fluorescence imaging of therapy-induced apoptosis for intraoperative surgical guidance may be a promising treatment strategy for metastatic ovarian cancer.
    PLoS ONE 02/2014; 9(2):e89968. DOI:10.1371/journal.pone.0089968 · 3.23 Impact Factor
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    • "Fluorescence-guided surgery is quickly gaining traction because it provides real-time assessment of normal and diseased tissues. A number of fluorescent image-guided surgery systems are in development, clinical trials, or are commercially available for use [7]. However, targeted fluorophore availability is currently limited, and a clinically viable nerve-specific fluorophore does not exist. "
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    ABSTRACT: Nerve damage is a major morbidity associated with numerous surgical interventions. Yet, nerve visualization continues to challenge even the most experienced surgeons. A nerve-specific fluorescent contrast agent, especially one with near-infrared (NIR) absorption and emission, would be of immediate benefit to patients and surgeons. Currently, there are only three classes of small molecule organic fluorophores that penetrate the blood nerve barrier and bind to nerve tissue when administered systemically. Of these three classes, the distyrylbenzenes (DSBs) are particularly attractive for further study. Although not presently in the NIR range, DSB fluorophores highlight all nerve tissue in mice, rats, and pigs after intravenous administration. The purpose of the current study was to define the pharmacophore responsible for nerve-specific uptake and retention, which would enable future molecules to be optimized for NIR optical properties. Structural analogs of the DSB class of small molecules were synthesized using combinatorial solid phase synthesis and commercially available building blocks, which yielded more than 200 unique DSB fluorophores. The nerve-specific properties of all DSB analogs were quantified using an ex vivo nerve-specific fluorescence assay on pig and human sciatic nerve. Results were used to perform quantitative structure-activity relationship (QSAR) modeling and to define the nerve-specific pharmacophore. All DSB analogs with positive ex vivo fluorescence were tested for in vivo nerve specificity in mice to assess the effect of biodistribution and clearance on nerve fluorescence signal. Two new DSB fluorophores with the highest nerve to muscle ratio were tested in pigs to confirm scalability.
    PLoS ONE 09/2013; 8(9):e73493. DOI:10.1371/journal.pone.0073493 · 3.23 Impact Factor
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