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Cover Neurosurgical Focus: Video

5-ALA fluorescence in indeterminate grade gliomas

Michael Müther and Walter Stummer

intensity of low-grade glioma fluorescence. 1 1:54 Generally, visible fluorescence is observed in 98%–100% of glioblastoma patients treated with 5-ALA. 2 , 3 In contrast, visible fluorescence is observed in approximately 75%–85% of all grade III gliomas and 16%–20% of grade II diffuse gliomas. 2 , 4 In those cases, 5-ALA fluorescence is reported to correlate with signal intensity on FET-PET. 2 , 5 , 6 Here, fluorescence was coregistered with the available preoperative imaging data using

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Cover Journal of Neurosurgery: Case Lessons

Awake resection of recurrent astroblastoma with intraoperative 5-ALA–induced fluorescence: illustrative case

Anthony Price, Sean O’Leary, Kseniia Malkova, Preston D’Souza, Christian Ogasawara, Michelle M Felicella, and Patrick J Karas

the current visit showed significant regrowth to 3.8 cm. The tumor was lobulated, T1 and T2 isointense, and with heterogeneous contrast enhancement at the anterior inferior aspect of the resection cavity with a component of mass effect on the left lateral ventricle atrium without midline shift ( Fig. 2 ). A left-sided awake craniotomy was performed ( Video 1 ) to remove the tumor while using speech mapping and 5-aminolevulinic acid (5-ALA). Speech mapping of the resection area showed no response

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Cover Journal of Neurosurgery

Fluorescence real-time kinetics of protoporphyrin IX after 5-ALA administration in low-grade glioma

Sadahiro Kaneko, Eric Suero Molina, Peter Sporns, Stephanie Schipmann, David Black, and Walter Stummer

T he optimal treatment for low-grade gliomas (LGGs) is a matter of ongoing debate. 5-Aminolevulinic acid (5-ALA) is a broadly used and well-established surgical adjunct in high-grade glioma (HGG) surgery. The randomized phase III multicenter approval study of 5-ALA is one of the most cited articles in neurosurgery. 1 This is not only due to the high clinical relevance in glioma surgery, but also due to the variable application of 5-ALA in translational research. However, the clinical

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Cover Journal of Neurosurgery

Molecularly targeted protease-activated probes for visualization of glioblastoma: a comparison with 5-ALA

Dora Konečná, Petr Výmola, Nikola Ternerová, Barbora Výmolová, Elena Garcia-Borja, Rosana Mateu, Filip Šroubek, Jan Pankrác, John C. Widen, Matthew Bogyo, David Netuka, Petr Bušek, and Aleksi Šedo

intraoperative MRI (iMRI), 8 intraoperative ultrasonography (iUSG), 9 and fluorescence-guided surgery (FGS). 10 , 11 Notably, FGS offers the advantage of enabling real-time visualization of tumor tissue during surgery. Currently, the only contrast agent widely used for FGS in GBMs is 5-aminolevulinic acid (5-ALA). 5-ALA accumulates in highly metabolically active tissues and is converted to protoporphyrin IX (PPIX). 12 After excitation with blue light (λ = 410–420 nm), PPIX emits light in the red

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Cover Neurosurgical Focus: Video

Contemporary intraoperative visualization for GBM with use of exoscope, 5-ALA fluorescence-guided surgery and tractography

Alexander J. Schupper, Jorge A. Roa, and Constantinos G. Hadjipanayis

Transcript 0:20 This video article shows the key technical aspects of the combined 3D exoscope with DTI tractography and 5-ALA fluorescence for high-grade glioma resection. 0:33 A 33-year-old male patient presents with refractory seizures following a prior brain biopsy consistent with a high-grade glioma. His neurological exam was initially significant for mild word-finding difficulties, otherwise nonfocal with no motor or sensory deficits and intact cranial nerves. 0

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Cover Journal of Neurosurgery

Limited utility of 5-ALA optical fluorescence in endoscopic endonasal skull base surgery: a multicenter retrospective study

Alexander Micko, Benjamin I. Rapoport, Brett E. Youngerman, Reginald P. Fong, Jennifer Kosty, Andrew Brunswick, Shane Shahrestani, Gabriel Zada, and Theodore H. Schwartz

acid (5-ALA), a compound of the porphyrin synthesis pathway, has been shown to improve resection rates and patient outcomes in high-grade gliomas (HGGs). The mechanism of fluorescence is via protoporphyrin IX, which accumulates in the intracellular space in tumor tissue and becomes visible through 405-nm–wavelength blue light. 7 , 8 The US FDA approved 5-ALA in 2017 as an intraoperative visualizing agent for patients with HGGs. 9 Due to these promising results, 5-ALA has also been applied

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Cover Journal of Neurosurgery

Use of 5-ALA fluorescence–guided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): a French multicenter randomized phase III study

Thiébaud Picart, Johan Pallud, Julien Berthiller, Chloé Dumot, Moncef Berhouma, Francois Ducray, Xavier Armoiry, Jennifer Margier, Pascale Guerre, Pascale Varlet, David Meyronet, Philippe Metellus, and Jacques Guyotat

of the quality of diffuse glioma resection remains a major consideration in neuro-oncology. 1 , 7 Given that the intraoperative identification of a marginal tumor remnant by the neurosurgeon’s unaided eye is not reliable, 8 several surgical tools including intraoperative image-based technologies (ultrasonography, MRI-based neuronavigation, or intraoperative MRI) have been developed. 9 , 10 The technique of 5-aminolevulinic acid (5-ALA) fluorescence–guided surgery (FGS) constitutes a chemical

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Cover Journal of Neurosurgery

Analysis of the surgical benefits of 5-ALA–induced fluorescence in intracranial meningiomas: experience in 204 meningiomas

Matthias Millesi, Barbara Kiesel, Mario Mischkulnig, Mauricio Martínez-Moreno, Adelheid Wöhrer, Stefan Wolfsberger, Engelbert Knosp, and Georg Widhalm

incomplete resection. Therefore, techniques to visualize residual tumor tissue during meningioma surgery are warranted in order to minimize the rate of tumor recurrence. In the last 2 decades, intraoperative visualization of malignant glioma tissue with assistance of the fluorescent dye 5-aminolevulinic acid (5-ALA) has been increasingly applied. 33 Oral administration of 5-ALA prior to surgery leads to visible intratumoral protoporphyrin IX (PpIX) fluorescence during resection. 32 In a multicenter

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Cover Journal of Neurosurgery

Influence of dexamethasone on visible 5-ALA fluorescence and quantitative protoporphyrin IX accumulation measured by fluorescence lifetime imaging in glioblastomas: is pretreatment obligatory before fluorescence-guided surgery?

Lisa I. Wadiura, David Reichert, Veronika Sperl, Alexandra Lang, Barbara Kiesel, Mikael Erkkilae, Adelheid Wöhrer, Julia Furtner, Thomas Roetzer, Rainer Leitgeb, Mario Mischkulnig, and Georg Widhalm

N eurosurgical resection is the initial treatment of choice in patients suffering from glioblastomas (GBMs). 1 , 2 In surgery of GBMs, the extent of resection is a key factor for patient prognosis. 1 , 3–5 Therefore, the aim of neurosurgical tumor resection is maximal safe removal of GBM tissue whenever possible. 1 , 3–5 In 1998, the use of 5-aminolevulinic acid (5-ALA)–induced fluorescence was introduced to the neurosurgical field for improved intraoperative visualization of GBM

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Cover Journal of Neurosurgery

Development and validation of a triple-LED surgical loupe device for fluorescence-guided resections with 5-ALA

Eric Suero Molina, Sönke J. Hellwig, Anna Walke, Astrid Jeibmann, Herbert Stepp, and Walter Stummer

F luorescence-guided resections (FGRs) performed using 5-aminolevulinic acid (5-ALA) have expanded the surgical armamentarium for malignant glioma. 1 This method is based on the visualization of protoporphyrin IX (PPIX) fluorescence induced by 5-ALA in malignant glioma tissue. The strength of the method is the fact that PPIX fluorescence, which is emitted in the red range (peak 635 nm) can be directly observed during surgery without having to rely on cameras and image processing (e