IntroductionFluorescence-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.MethodsReview of the literature.ResultsA 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.ConclusionWe 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.

Introduction: Acridine orange (AO) was first extracted from coal tar in the late nineteenth century and was used as a fluorescent dye. In this paper, we review emergent research about novel applications of AO for fluorescence surgery and cancer therapy.Materials and methods: We performed a systematic search in the MEDLINE, PubMed, Cochrane library, Google Scholar, Embase, Web of Science, and Scopus database using combinations of the term “acridine orange” with the following: “surgical oncology,” “neuropathology,” “microsurgery,” “intraoperative fluorescence,” “confocal microscopy,” “pathology,” “endomicroscopy,” “guidance,” “fluorescence guidance,” “oncology,” “surgery,” “neurooncology,” and “photodynamic therapy.” Peer-reviewed articles published in English were included in this review. We have also scanned references for relevant articles.Results: We have reviewed studies on the various application of AO in microscopy, endomicroscopy, intraoperative fluorescence guidance, photodynamic therapy, sonodynamic therapy, radiodynamic therapy.Conclusion: Although the number of studies on the clinical use of AO is limited, pilot studies have demonstrated the safety and feasibility of its application as an intraoperative fluorescent dye and as a novel photo- and radio-sensitizator. Further clinical studies are necessary to more definitively assess the clinical benefit AO-based fluorescence guidance, therapy for sarcomas, and to establish feasibility of this new approach for the treatment of other tumor types.

PurposeTo assess the utility of apparent diffusion coefficient (ADC) maps for the assessment of patients with advanced degenerative lumbar spine disease and describe characteristic features of ADC maps in various degenerative lumbar spinal conditions.MethodsT1-weighted, T2-weighted and diffusion weighted (DWI) MR images of 100 consecutive patients admitted to the spinal surgery service were assessed. ADC maps were generated from DWI images using Osyrix software. The ADC values and characteristic ADC maps were assessed in the regions of interest over the different pathological entities of the lumbar spine.ResultsThe study included 452 lumbar vertebral segments available for analysis of ADCs. Characteristic ADC map features were identified for protrusion, extrusion and sequester types of lumbar disk herniations, spondylolisthesis, reactive Modic endplate changes, Pfirrmann grades of IVD degeneration, and compromised spinal nerves. Compromised nerve roots had significantly higher mean ADC values than adjacent (p < 0.001), contralateral (p < 0.001) or adjacent contralateral (p < 0.001) nerve roots. Compared to the normal bone marrow, Modic I changes showed higher ADC values (p = 0.01) and Modic 2 changes showed lower ADC values (p = 0.02) respectively. ADC values correlated with the Pfirrmann grading, however differed from herniated and non-herniated disks of the matched Pfirrmann 3 and 4 grades.ConclusionQuantitative and qualitative evaluation of ADC mapping may provide additional useful information regarding the fluid dynamics of the degenerated spine and may complement standard MRI imaging protocol for the comprehensive assessment of surgical patients with lumbar spine pathology. ADC maps were advantageous in differentiating reactive bone marrow changes, and more precise assessment of the disk degeneration state. ADC mapping of compressed nerve roots showed promise but requires further investigation on a larger cohort of patients.

Introduction: In this study, magnetic resonance imaging data was used to (1) model IVD-specific gradients of glucose, oxygen, lactate, and pH; and (2) investigate possible effects of covariate factors (i.e., disc geometry, and mean apparent diffusion coefficient values) on the IVD's microenvironment. Mathematical modeling of the patient's specific IVD microenvironment could be important when selecting patients for stem cell therapy due to the increased nutrient demand created by that treatment.Materials and Methods: Disc geometry and water diffusion coefficients were extracted from MRIs of 37 patients using sagittal T1-weighted images, T2-weighted images, and ADC Maps. A 2-D steady state finite element mathematical model was developed in COM-SOL Multiphysics ® 5.4 to compute concentration maps of glucose, oxygen, lactate and pH.Results: Concentration of nutrients (i.e., glucose, and oxygen) dropped with increasing distance from the cartilaginous endplates (CEP), whereas acidity levels increased. Most discs experienced poor nutrient levels along with high acidity values in the inner annulus fibrosus (AF). The disc's physiological microenvironment became more deficient as degeneration progressed. For example, minimum glucose concentration in grade 4 dropped by 31.1% compared to grade 3 (p < 0.0001). The model further suggested a strong effect of the following parameters: disc size, AF and CEP diffusivities, metabolic reactions, and cell density on solute concentrations in the disc (p < 0.05). Conclusion:The significance of this work implies that the individual morphology and physiological conditions of each disc, even among discs of the same Pfirrmann grade, should be evaluated when modeling IVD solute concentrations.

BackgroundFluorescein sodium (FNa) is a fluorescence agent used with a wide-field operating microscope for intraoperative guidance and with confocal laser endomicroscopy (CLE) to evaluate brain tissue. Susceptibility of FNa to degradation over time may affect CLE image quality during prolonged surgeries. This study describes improved characteristics of CLE images after intraoperative redosing with FNa.MethodsA retrospective analysis was performed using CLE images obtained ex vivo from samples obtained during tumor resections with FNa-based fluorescence guidance with a wide-field operating microscope. The comparison groups included CLE images acquired after FNa redosing (redose imaging group), images from the same patients acquired after the initial FNa dose (initial-dose imaging group), and images from patients in whom redosing was not used (single-dose imaging group). A detailed assessment of image quality and interpretation regarding different FNa dosage and timing of imaging after FNa administration was conducted for all comparison groups.ResultsThe brightest and most contrasting images were observed in the redose group compared to the initial-dose and single-dose groups (P&lt;0.001). The decay of FNa signal negatively correlated with brightness (rho = -0.52, P&lt;0.001) and contrast (rho = -0.57, P&lt;0.001). Different doses of FNa did not significantly affect the brightness (P=0.15) or contrast (P=0.09) in CLE images. As the mean timing of imaging increased, the percentage of accurately diagnosed images decreased (P=0.03).ConclusionsThe decay of the FNa signal is directly associated with image brightness and contrast. The qualitative interpretation scores of images were highest for the FNa redose imaging group. Redosing with FNa to improve the utility of CLE imaging should be considered a safe and beneficial strategy during prolonged surgeries.

No abstract

OBJECTIVE Microsurgical training remains indispensable to master cerebrovascular bypass procedures, but simulation models for training that accurately replicate microanastomosis in narrow, deep-operating corridors are lacking. Seven simulation bypass scenarios were developed that included head models in various surgical positions with premade approaches, simulating the restrictions of the surgical corridors and hand positions for microvascular bypass training. This study describes these models and assesses their validity. METHODS Simulation models were created using 3D printing of the skull with a designed craniotomy. Brain and external soft tissues were cast using a silicone molding technique from the clay-sculptured prototypes. The 7 simulation scenarios included: 1) temporal craniotomy for a superficial temporal artery (STA)–middle cerebral artery (MCA) bypass using the M4 branch of the MCA; 2) pterional craniotomy and transsylvian approach for STA-M2 bypass; 3) bifrontal craniotomy and interhemispheric approach for side-to-side bypass using the A3 branches of the anterior cerebral artery; 4) far lateral craniotomy and transcerebellomedullary approach for a posterior inferior cerebellar artery (PICA)–PICA bypass or 5) PICA reanastomosis; 6) orbitozygomatic craniotomy and transsylvian-subtemporal approach for a posterior cerebral artery bypass; and 7) extended retrosigmoid craniotomy and transcerebellopontine approach for an occipital artery–anterior inferior cerebellar artery bypass. Experienced neurosurgeons evaluated each model by practicing the aforementioned bypasses on the models. Face and content validities were assessed using the bypass participant survey. RESULTS A workflow for model production was developed, and these models were used during microsurgical courses at 2 neurosurgical institutions. Each model is accompanied by a corresponding prototypical case and surgical video, creating a simulation scenario. Seven experienced cerebrovascular neurosurgeons practiced microvascular anastomoses on each of the models and completed surveys. They reported that actual anastomosis within a specific approach was well replicated by the models, and difficulty was comparable to that for real surgery, which confirms the face validity of the models. All experts stated that practice using these models may improve bypass technique, instrument handling, and surgical technique when applied to patients, confirming the content validity of the models. CONCLUSIONS The 7 bypasses simulation set includes novel models that effectively simulate surgical scenarios of a bypass within distinct deep anatomical corridors, as well as hand and operator positions. These models use artificial materials, are reusable, and can be implemented for personal training and during microsurgical courses.

No abstract