Current Optics and Photonics

Optical Society of Korea (한국광학회)
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A Multi-detection Fluorescence Dye with 5-ALA and ICG Using Modified Light Emitting Diodes

  • Yoon, Kicheol (Department of Biomedical Engineering, College of Medicine & Health Science, Gachon University) ;
  • Kim, Eunji (Department of Biomedical Engineering, College of Medicine & Health Science, Gachon University) ;
  • Kim, Kwanggi (Department of Biomedical Engineering, College of Medicine & Health Science, Gachon University) ;
  • Lee, Seunghoon (Department of Neurosurgery, Daejeon Eulji Medical Center (Eulji University Hospital)) ;
  • Yoo, Heon (Neuro-Oncology Clinic, Center for Specific Organs Center, National Cancer Center)
  • Received : 2018.09.18
  • Accepted : 2019.05.09
  • Published : 2019.06.25
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Abstract

Extensive tumor resection accompanied by radiotherapy and chemotherapy is the standard of care for malignant gliomas. However, there is a significant obstacle to the complete resection of the tumor due to the difficulty of distinguishing tumor and normal brain tissue with a conventional surgical microscope. Recently, multiple studies have shown the possibility of fluorescence-guided surgery in malignant gliomas. The most used fluorescence dyes for brain tumor surgery are 5-aminolevulinic acid (5-ALA) and indocyanine green (ICG). In this paper, a new fluorescence guided operation system, which can detect both 5-ALA and ICG fluorescent images simultaneously, is presented. This operation system consists of light emitting diodes (LEDs) which emits 410 nm and 740 nm wavelengths. We have performed experiments on rats in order to verify the operation of the newly developed operation system. Oral administration and imaging were performed to observe the fluorescence of 5-ALA and ICG fluorescence in rats. When LEDs at wavelengths of 410 nm and 740 nm were irradiated on rats, 628 nm wavelength with a violet fluorescence color and 825 nm wavelength with a red fluorescence color were expressed in 5-ALA and ICG fluorescent material, respectively, thus we were able to distinguish the tumor tissues easily. Previously, due to the poor resolution of the conventional surgical microscope and the fact that the color of the vein is similar to that of the tumor, the tumor resection margin was not easy to observe, thus increasing the likelihood for cancer recurrence. However, when the tumor is observed through the fluorescence guided operation system, it is possible to easily distinguish the color with the naked eye and it can be completely removed. Therefore, it is expected that surgical removal of cancerous tumors will be possible and surgical applications and surgical microscopes for cancer tumor removal surgery will be promising in the future.

Keywords

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FIG. 1. Structure of the surgical fluorescence microscope (a) figuration (b) block diagram.

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FIG. 2. Structure of the LEDs module (a) measurement results (b) structure.

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FIG. 4. Measurement result for 5-ALA fluorescent image of nude mouse tumors (a) without fluorescent dye (b) fluorescein dye.

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FIG. 5. Analysis of fluorescent wavelength, (a) 5-ALA (protoporphyrin IX) (b) ICG.

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FIG. 3. Setting of animal experimentation.

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FIG. 6. Chemical structure of the indocynine green fluorescein emission.

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FIG. 7. Formation of PpIX fluorescein protein at 5-ALA on tumor.

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FIG. 8. Experimental results for ICG and 5-ALA fluorescein emission image with blood flow and tumor.

TABLE 1. Specifications of the LEDs

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TABLE 2. Specifications of the SBIG STF-8300C color CCD camera

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TABLE 3. Parameter of fluorescence microscope experiment

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