Editorial: Applications of Fluorescence in Surgery and Interventional Diagnostics

Department of Neurosurgery, New Jersey Medical School, Rutgers University, Newark, NJ, United States, 2 The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, United States, Center for Advanced Digestive Care, Weill Cornell Medicine, New York, NY, United States, Departments of Surgery and Pharmacology, University of California, San Diego, San Diego, CA, United States


Applications of Fluorescence in Surgery and Interventional Diagnostics
Augmentation of the surgeon's and interventionalist's vision by advanced optical imaging, including fluorescence guidance [i.e., fluorescence-guided surgery (FGS)], is the basis for multiple innovations that will transform the workflow of all subspecialties of surgery and interventional diagnostics. Advanced optical imaging could solve multiple practical problems, making normal and abnormal tissue and cellular structures that are otherwise indistinguishable to an unaided human eye visible and making surgery and interventions for patients safer, more efficient, and successful.
In this Frontiers issue, "Applications of Fluorescence in Surgery and Interventional Diagnostics, " we are privileged to present a collection of 34 open-access publications that describe the frontiers in research and practice of fluorescence imaging in medicine. These articles were selected through an open peer-review process that unites experts in the field, including 220 authors and 60 reviewers and editors.
The first series of articles addresses the frontiers of wide-field fluorescence imaging in neurosurgical oncology and includes works on the major fluorophores: 5-aminolevulinic acid (5-ALA), fluorescein sodium, indocyanine green (ICG), and talaporfin sodium. 5-ALA-based imaging has seen significant growth in recent years, reflected by the high number of articles submitted for publication. Beginning with a historical review on how 5-ALA was introduced into practice . In an invited opinion paper, Duffau discusses the role of fluorescence guidance in the surgery of malignant brain tumors in the context of the current trend for "maximal function-based resections." It could be that the combination of both functional imaging or mapping and fluorescence techniques would be advantageous for a balanced and informed solution to maximize the goals of the surgery. Specifically, this could be achieved by first localizing the brain function through awake or asleep mapping to ensure the safety of resection. Second, localizing tumor extension through advanced optical imaging could ensure no unintentionally missed tumor tissue residuals.
Fluorescence and advance optical guidance will remain relevant and continue advancing within the surgical field as long as surgery remains a part of the neurooncology tumor management strategy. Future developments include more specific optical labels, such as fluorescently labeled peptides and nanoparticles to visualize abnormal and normal tissue better, for example, for peripheral nerves (1), or drug-free optical molecular imaging tools to visualize and discriminate normal (2)  . These papers describe technologies for optical biopsies that are either FDA-approved or are at various stages of development. An exciting development within this realm is improving and optimizing the resection of malignant or invasive tumors by bringing a portable visualizing probe within the surgeon's hand that is a comfortable size and displays real-time in vivo fluorescence imaging to detect abnormal histoarchitecture. At least for brain surgery, although such technology could be used to extend the resection margins, which has correlated with increased survival, it may also be used to inform the surgeon of the tumor boundary and thus where to stop resection. These and other technologies within an operating room environment and incorporated into the surgical and pathology workflows effectively link the pathological consultation directly into the operating room. Theoretically, such technology could replace frozen section biopsies with optical biopsies, thereby increasing the yield of biopsies and the speed of surgery. Such technologies will include computer-aided image analysis (Izadyyazdanabadi et al.) and related image assessments that will guide and improve intraoperative diagnostics.
The third set of papers addresses the nuances of fluorescence imaging for vascular neurosurgery. Papers describe the evidence, techniques, and practical pearls of applying ICG contrast to augment visualization of cerebral . These innovative clinical technologies include wide-field and small-field confocal imaging tools with fluorescein and ICG contrast. These fluorescence applications for surgery were among the first to be incorporated into disease diagnostics and therapeutics, such as gastrointestinal disease. They prompted the developments that launched surgical fluorescence handheld endoscopic imaging technology into other surgical disciplines, such as neurosurgery. These imaging techniques are a routine part of disease diagnostics and monitoring in many global locations, especially for precancerous and cancerous lesion management.
This constellation of basic, translational, and clinical papers will facilitate the interdisciplinary exchange of knowledge and will aid in the further progress of advanced opticalaided technologies. These authors and colleagues will lead advanced imaging efforts and champion innovations in optical navigation to improve patient outcomes and benefit healthcare systems.

AUTHOR CONTRIBUTIONS
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.