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Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery

Objective: Fluorescence dyes are increasingly used in brain tumor surgeries, and thus the development of simulation models is important for teaching neurosurgery trainees how to perform fluorescence-guided operations. We aimed to create a tumor model for fluorescence-guided surgery in high-grade gli...

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Autores principales: Valli, Daniel, Belykh, Evgenii, Zhao, Xiaochun, Gandhi, Sirin, Cavallo, Claudio, Martirosyan, Nikolay L., Nakaji, Peter, Lawton, Michael T., Preul, Mark C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706957/
https://www.ncbi.nlm.nih.gov/pubmed/31475107
http://dx.doi.org/10.3389/fonc.2019.00748
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author Valli, Daniel
Belykh, Evgenii
Zhao, Xiaochun
Gandhi, Sirin
Cavallo, Claudio
Martirosyan, Nikolay L.
Nakaji, Peter
Lawton, Michael T.
Preul, Mark C.
author_facet Valli, Daniel
Belykh, Evgenii
Zhao, Xiaochun
Gandhi, Sirin
Cavallo, Claudio
Martirosyan, Nikolay L.
Nakaji, Peter
Lawton, Michael T.
Preul, Mark C.
author_sort Valli, Daniel
collection PubMed
description Objective: Fluorescence dyes are increasingly used in brain tumor surgeries, and thus the development of simulation models is important for teaching neurosurgery trainees how to perform fluorescence-guided operations. We aimed to create a tumor model for fluorescence-guided surgery in high-grade glioma (HGG). Methods: The tumor model was generated by the following steps: creating a tumor gel with a similar consistency to HGG, selecting fluorophores at optimal concentrations with realistic color, mixing the fluorophores with tumor gel, injecting the gel into fresh pig/sheep brain, and testing resection of the tumor model under a fluorescence microscope. The optimal tumor gel was selected among different combinations of agar and gelatin. The fluorophores included fluorescein, indocyanine green (ICG), europium, chlorin e6 (Ce6), and protoporphyrin IX (PpIX). The tumor model was tested by neurosurgeons and neurosurgery trainees, and a survey was used to assess the validity of the model. In addition, the photobleaching phenomenon was studied to evaluate its influence on fluorescence detection. Results: The best tumor gel formula in terms of consistency and tactile response was created using 100 mL water at 100°C, 0.5 g of agar, and 3 g of gelatin mixed thoroughly for 3 min. An additional 1 g of agar was added when the tumor gel cooled to 50°C. The optimal fluorophore concentration ranges were fluorescein 1.9 × 10(−4) to 3.8 × 10(−4) mg/mL, ICG 4.9 × 10(−3) to 9.8 × 10(−3) mg/mL, europium 7.0 × 10(−2) to 1.4 × 10(−1) mg/mL, Ce6 2.2 × 10(−3) to 4.4 × 10(−3) mg/mL, and PpIX 1.8 × 10(−2) to 3.5 × 10(−2) mg/mL. No statistical differences among fluorophores were found for face validity, content validity, and fluorophore preference. Europium, ICG, and fluorescein were shown to be relatively stable during photobleaching experiments, while chlorin e6 and PpIX had lower stability. Conclusions: The model can efficiently highlight the “tumor” with 3 different colors—green, yellow, or infrared green with color overlay. These models showed high face and content validity, although there was no significant difference among the models regarding the degree of simulation and training effectiveness. They are useful educational tools for teaching the key concepts of intra-axial tumor resection techniques, such as subpial dissection and nuances of fluorescence-guided surgery.
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spelling pubmed-67069572019-08-30 Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery Valli, Daniel Belykh, Evgenii Zhao, Xiaochun Gandhi, Sirin Cavallo, Claudio Martirosyan, Nikolay L. Nakaji, Peter Lawton, Michael T. Preul, Mark C. Front Oncol Oncology Objective: Fluorescence dyes are increasingly used in brain tumor surgeries, and thus the development of simulation models is important for teaching neurosurgery trainees how to perform fluorescence-guided operations. We aimed to create a tumor model for fluorescence-guided surgery in high-grade glioma (HGG). Methods: The tumor model was generated by the following steps: creating a tumor gel with a similar consistency to HGG, selecting fluorophores at optimal concentrations with realistic color, mixing the fluorophores with tumor gel, injecting the gel into fresh pig/sheep brain, and testing resection of the tumor model under a fluorescence microscope. The optimal tumor gel was selected among different combinations of agar and gelatin. The fluorophores included fluorescein, indocyanine green (ICG), europium, chlorin e6 (Ce6), and protoporphyrin IX (PpIX). The tumor model was tested by neurosurgeons and neurosurgery trainees, and a survey was used to assess the validity of the model. In addition, the photobleaching phenomenon was studied to evaluate its influence on fluorescence detection. Results: The best tumor gel formula in terms of consistency and tactile response was created using 100 mL water at 100°C, 0.5 g of agar, and 3 g of gelatin mixed thoroughly for 3 min. An additional 1 g of agar was added when the tumor gel cooled to 50°C. The optimal fluorophore concentration ranges were fluorescein 1.9 × 10(−4) to 3.8 × 10(−4) mg/mL, ICG 4.9 × 10(−3) to 9.8 × 10(−3) mg/mL, europium 7.0 × 10(−2) to 1.4 × 10(−1) mg/mL, Ce6 2.2 × 10(−3) to 4.4 × 10(−3) mg/mL, and PpIX 1.8 × 10(−2) to 3.5 × 10(−2) mg/mL. No statistical differences among fluorophores were found for face validity, content validity, and fluorophore preference. Europium, ICG, and fluorescein were shown to be relatively stable during photobleaching experiments, while chlorin e6 and PpIX had lower stability. Conclusions: The model can efficiently highlight the “tumor” with 3 different colors—green, yellow, or infrared green with color overlay. These models showed high face and content validity, although there was no significant difference among the models regarding the degree of simulation and training effectiveness. They are useful educational tools for teaching the key concepts of intra-axial tumor resection techniques, such as subpial dissection and nuances of fluorescence-guided surgery. Frontiers Media S.A. 2019-08-16 /pmc/articles/PMC6706957/ /pubmed/31475107 http://dx.doi.org/10.3389/fonc.2019.00748 Text en Copyright © 2019 Valli, Belykh, Zhao, Gandhi, Cavallo, Martirosyan, Nakaji, Lawton and Preul. http://creativecommons.org/licenses/by/4.0/ 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) and the copyright owner(s) 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.
spellingShingle Oncology
Valli, Daniel
Belykh, Evgenii
Zhao, Xiaochun
Gandhi, Sirin
Cavallo, Claudio
Martirosyan, Nikolay L.
Nakaji, Peter
Lawton, Michael T.
Preul, Mark C.
Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery
title Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery
title_full Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery
title_fullStr Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery
title_full_unstemmed Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery
title_short Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery
title_sort development of a simulation model for fluorescence-guided brain tumor surgery
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706957/
https://www.ncbi.nlm.nih.gov/pubmed/31475107
http://dx.doi.org/10.3389/fonc.2019.00748
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