5-aminolevulinic acid, fluorescein sodium, and indocyanine green for glioma margin detection: analysis of operating wide-field and confocal microscopy in glioma models of various grades
Belykh E. Bardonova L. Abramov I. Byvaltsev V.A. Kerymbayev T. Yu K. Healey D.R. Luna-Melendez E. Deneen B. Mehta S. Liu J.K. Preul M.C.
2023Frontiers Media S.A.
Frontiers in Oncology
2023#13
Introduction: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques. Methods: Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an in utero electroporation model with and without red fluorescence protein (IUE +RFP and IUE -RFP, respectively) (intermediate-to-low-grade model). Animals underwent 5-ALA, FNa, and ICG injections and craniectomy. Brain tissue samples underwent fluorescent imaging using a wide-field operative microscope and a benchtop confocal microscope and were submitted for histologic analysis. Results: Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of the normal brain. In low-grade gliomas, wide-field imaging cannot detect ICG staining, can detect FNa in only 50% of specimens, and is not sensitive enough for PpIX detection. With confocal imaging of low-intermediate grade glioma models, PpIX outperformed FNa. Discussion: Overall, compared to wide-field imaging, confocal microscopy significantly improved diagnostic accuracy and was better at detecting low concentrations of PpIX and FNa, resulting in improved tumor delineation. Neither PpIX, FNa, nor ICG delineated all tumor boundaries in studied tumor models, which emphasizes the need for novel visualization technologies and molecular probes to guide glioma resection. Simultaneous administration of 5-ALA and FNa with use of cellular-resolution imaging modalities may provide additional information for margin detection and may facilitate maximal glioma resection. Copyright
5-aminolevulinic acid , fluorescein sodium , fluorescence guided surgery , glioma , indocyanine green , laser scanning microscopy , protoporphyrin IX
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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
Department of Neurosurgery, New Jersey Medical School, Rutgers University, Newark, NJ, United States
Department of Neurosurgery, Irkutsk State Medical University, Irkutsk, Russian Federation
Department of Neurosurgery, JSC “National Scientific Center of Neurosurgery”, Nur-Sultan, Kazakhstan
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States
Department of Research Imaging, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, United States
Ivy Brain Tumor Research Center, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, United States
The Loyal and Edith Davis Neurosurgical Research Laboratory
Department of Neurosurgery
Department of Neurosurgery
Department of Neurosurgery
Center for Cell and Gene Therapy
Department of Research Imaging
Ivy Brain Tumor Research Center
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