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      Intraoperative Fluorescence Imaging for Personalized Brain Tumor Resection: Current State and Future Directions

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          Abstract

          Introduction

          Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies.

          Methods

          Review of the literature.

          Results

          A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.

          Conclusion

          We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

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          Most cited references184

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          Computerized transverse axial scanning (tomography). 1. Description of system.

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            Glioma extent of resection and its impact on patient outcome.

            There is still no general consensus in the literature regarding the role of extent of glioma resection in improving patient outcome. Although the importance of resection in obtaining tissue diagnosis and alleviating symptoms is clear, a lack of Class I evidence prevents similar certainty in assessing the influence of extent of resection. We reviewed every major clinical publication since 1990 on the role of extent of resection in glioma outcome. Twenty-eight high-grade glioma articles and 10 low-grade glioma articles were examined in terms of quality of evidence, expected extent of resection, and survival benefit. Despite persistent limitations in the quality of data, mounting evidence suggests that more extensive surgical resection is associated with longer life expectancy for both low- and high-grade gliomas.
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              Near-infrared fluorescence: application to in vivo molecular imaging.

              Molecular imaging often relies on the use of targeted and activatable reporters to quantitate and visualize targets, biological processes, and cells in vivo. The use of optical probes with near-infrared fluorescence allows for improved photon penetration through tissue and minimizes the effects of tissue autofluorescence. There are several parameters that define the effectiveness of imaging agents in vivo. These factors include probe targeting, activation, pharmacokinetics, biocompatibility, and photophysics. Recent advances in our understanding of these variables as they pertain to the application of optical reporters for in vivo imaging are discussed in this review. 2009 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Surg
                Front Surg
                Front. Surg.
                Frontiers in Surgery
                Frontiers Media S.A.
                2296-875X
                17 October 2016
                2016
                : 3
                : 55
                Affiliations
                [1] 1Department of Neurosurgery, St. Joseph’s Hospital and Medical Center, Barrow Neurological Institute , Phoenix, AZ, USA
                [2] 2School of Life Sciences, Arizona State University , Tempe, AZ, USA
                [3] 3Laboratory of Neurosurgery, Irkutsk Scientific Center of Surgery and Traumatology , Irkutsk, Russia
                [4] 4Irkutsk State Medical University , Irkutsk, Russia
                [5] 5University of Arizona College of Medicine – Phoenix , Phoenix, AZ, USA
                Author notes

                Edited by: Eberval Figueiredo, Universidade de São Paulo, Brazil

                Reviewed by: Yasunori Fujimoto, Osaka University, Japan; Andrei Fernandes Joaquim, University of Campinas, Brazil

                *Correspondence: Mark C. Preul, neuropub@ 123456dignityhealth.org

                Specialty section: This article was submitted to Neurosurgery, a section of the journal Frontiers in Surgery

                Article
                10.3389/fsurg.2016.00055
                5066076
                27800481
                06e3ef7b-7bb8-4e22-b2b1-fbd250450feb
                Copyright © 2016 Belykh, Martirosyan, Yagmurlu, Miller, Eschbacher, Izadyyazdanabadi, Bardonova, Byvaltsev, Nakaji and Preul.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 June 2016
                : 12 September 2016
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 223, Pages: 27, Words: 18429
                Funding
                Funded by: Barrow Neurological Foundation 10.13039/100009797
                Categories
                Surgery
                Review

                5-ala,confocal,endomicroscopy,fluorescein,fluorescence-guided surgery,fluorescent probe,glioma,icg

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