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

被引:8
作者
Valli, Daniel [1 ]
Belykh, Evgenii [1 ]
Zhao, Xiaochun [1 ]
Gandhi, Skin [1 ]
Cavallo, Claudio [1 ]
Martirosyan, Nikolay L. [2 ]
Nakaji, Peter [1 ]
Lawton, Michael T. [1 ]
Preul, Mark C. [1 ]
机构
[1] St Josephs Hosp, Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ 85013 USA
[2] Univ Arizona, Dept Neurosurg, Tucson, AZ USA
来源
FRONTIERS IN ONCOLOGY | 2019年 / 9卷
关键词
europium; fluorescein; fluorescence-guided tumor surgery; fluorophores; high-grade glioma; indocyanine green; protoporphyrin IX; tumor model; PHOTODYNAMIC THERAPY; GLIOMA; RESECTION; SODIUM; 5-ALA; ACID;
D O I
10.3389/fonc.2019.00748
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 degrees 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 degrees C. The optimal fluorophore concentration ranges were fluorescein 1.9 x 10(-4) to 3.8 x 10(-4) mg/mL, ICG 4.9 x 10(-3) to 9.8 x 10(-3) mg/mL, europium 7.0 x 10(-2) to 1.4 x 10(-1) mg/mL, Ce6 2.2 x 10(-3) to 4.4 x 10(-3) mg/mL, and PpIX 1.8 x 10(-2) to 3.5 x 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.
引用
收藏
页数:14
相关论文
共 47 条
[31]   Hiding in the Shadows: CPOX Expression and 5-ALA Induced Fluorescence in Human Glioma Cells [J].
Pustogarov, Nikolay ;
Panteleev, Dmitriy ;
Goryaynov, Sergey A. ;
Ryabova, Anastasia V. ;
Rybalkina, Ekaterina Y. ;
Revishchin, Alexander ;
Potapov, Alexander A. ;
Pavlova, Galina .
MOLECULAR NEUROBIOLOGY, 2017, 54 (07) :5699-5708
[32]   5-Aminolevulinic Acid Guided Sampling of Glioblastoma Microenvironments Identifies Pro-Survival Signaling at Infiltrative Margins [J].
Ross, James L. ;
Cooper, Lee A. D. ;
Kong, Jun ;
Gutman, David ;
Williams, Merete ;
Tucker-Burden, Carol ;
McCrary, Myles R. ;
Bouras, Alexandros ;
Kaluzova, Milota ;
Dunn, William D., Jr. ;
Duong, Duc ;
Hadjipanayis, Constantinos G. ;
Brat, Daniel J. .
SCIENTIFIC REPORTS, 2017, 7
[33]  
Sabel M., 2017, GETTING READY BRAIN, DOI [10.1055/b-006-149701, DOI 10.1055/B-006-149701]
[34]  
Schindelin J, 2012, NAT METHODS, V9, P676, DOI [10.1038/NMETH.2019, 10.1038/nmeth.2019]
[35]   Simultaneous fluorescein sodium and 5-ALA in fluorescence-guided glioma surgery [J].
Schwake, Michael ;
Stummer, Walter ;
Molina, Eric Jose Suero ;
Wolfer, Johannes .
ACTA NEUROCHIRURGICA, 2015, 157 (05) :877-879
[36]   Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results [J].
Senders, Joeky T. ;
Muskens, Ivo S. ;
Schnoor, Rosalie ;
Karhade, Aditya V. ;
Cote, David J. ;
Smith, Timothy R. ;
Broekman, Marike L. D. .
ACTA NEUROCHIRURGICA, 2017, 159 (01) :151-167
[37]   Optical pH measurement system using a single fluorescent dye for assessing susceptibility to dental caries [J].
Sharma, Manuja ;
Graham, Jasmine Y. ;
Walczak, Philip A. ;
Nguyen, Ryan ;
Lee, Lauren K. ;
Carson, Matthew D. ;
Nelson, Leonard Y. ;
Patel, Shwetak N. ;
Xu, Zheng ;
Seibel, Eric J. .
JOURNAL OF BIOMEDICAL OPTICS, 2019, 24 (01)
[38]   Intraoperative Photodynamic Diagnosis Using Talaporfin Sodium Simultaneously Applied for Photodynamic Therapy against Malignant Glioma: A Prospective Clinical Study [J].
Shimizu, Kazuhide ;
Nitta, Masayuki ;
Komori, Takashi ;
Maruyama, Takashi ;
Yasuda, Takayuki ;
Fujii, Yu ;
Masamune, Ken ;
Kawamata, Takakazu ;
Maehara, Taketoshi ;
Muragaki, Yoshihiro .
FRONTIERS IN NEUROLOGY, 2018, 9
[39]   Photodynamic therapy with talaporfin sodium induces dose-dependent apoptotic cell death in human glioma cell lines [J].
Tsutsumi, Masateru ;
Miki, Yuichi ;
Akimoto, Jiro ;
Haraoka, Jo ;
Aizawa, Katsuo ;
Hirano, Kazuya ;
Beppu, Masatoshi .
PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY, 2013, 10 (02) :103-110
[40]  
Tzerkovsky D. A., 2014, Experimental Oncology, V36, P85