Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5-ALA)–induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection.
Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence.
Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses.
Intraoperative confocal microscopy can visualize cellular 5-ALA–induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors' institution.
Abbreviations used in this paper: 5-ALA = 5-aminolevulinic acid; BALANCE = Barrow ALA Intraoperative Confocal Evaluation; BNI = Barrow Neurological Institute; EOR = extent of resection; GTR = gross-total resection; HGG = high-grade glioma; LGG = low-grade glioma; NIHSS = National Institutes of Health Stroke Scale; ROI = region of interest.
Address correspondence to: Nader Sanai, M.D., Division of Neurosurgical Oncology, Barrow Brain Tumor Research Center, Barrow Neurological Institute, 2910 North Third Avenue, Phoenix, Arizona 85013. email: firstname.lastname@example.org.
Please include this information when citing this paper: published online July 15, 2011; DOI: 10.3171/2011.6.JNS11252.
BrownPDMaurerMJRummansTAPollockBEBallmanKVSloanJA: A prospective study of quality of life in adults with newly diagnosed high-grade gliomas: the impact of the extent of resection on quality of life and survival. Neurosurgery57:495–5042005
CoenenVAKringsTWeidemannJHansFJReinacherPGilsbachJM: Sequential visualization of brain and fiber tract deformation during intracranial surgery with threedimensional ultrasound: an approach to evaluate the effect of brain shift. Neurosurgery56:1 Suppl133–1412005
IshiharaRKatayamaYWatanabeTYoshinoAFukushimaTSakataniK: Quantitative spectroscopic analysis of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence intensity in diffusely infiltrating astrocytomas. Neurol Med Chir (Tokyo)47:53–572007
JohannesenTBLangmarkFLoteK: Progress in long-term survival in adult patients with supratentorial low-grade gliomas: a population-based study of 993 patients in whom tumors were diagnosed between 1970 and 1993. J Neurosurg99:854–8622003
KrishnanRRaabeAHattingenESzelenyiAYahyaHHermannE: Functional magnetic resonance imaging-integrated neuronavigation: correlation between lesion-to-motor cortex distance and outcome. Neurosurgery55:904–9052004
KurimotoMHayashiNKamiyamaHNagaiSShibataTAsahiT: Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study. Minim Invasive Neurosurg47:278–2832004
LiaoHNoguchiMMaruyamaTMuragakiYKobayashiEIsekiH: An integrated diagnosis and therapeutic system using intra-operative 5-aminolevulinic-acid-induced fluorescence guided robotic laser ablation for precision neurosurgery. Med Image Anal[epub ahead of print]2010
McGirtMJChaichanaKLAttenelloFJWeingartJDThanKBurgerPC: Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery63:700–7082008
PamirMNOzdumanKDinçerAYildizEPekerSOzekMM: First intraoperative, shared-resource, ultrahigh-field 3-Tesla magnetic resonance imaging system and its application in low-grade glioma resection. Clinical article. J Neurosurg112:57–692010
ReithmeierTKrammerMGumprechtHGerstnerWLumentaCB: Neuronavigation combined with electrophysiological monitoring for surgery of lesions in eloquent brain areas in 42 cases: a retrospective comparison of the neurological outcome and the quality of resection with a control group with similar lesions. Minim Invasive Neurosurg46:65–712003
ShawEArusellRScheithauerBO'FallonJO'NeillBDinapoliR: Prospective randomized trial of low-versus high-dose radiation therapy in adults with supratentorial lowgrade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol20:2267–22762002
StummerWPichlmeierUMeinelTWiestlerODZanellaFReulenHJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol7:392–4012006
UnsgaardGSelbekkTBrostrup MüllerTOmmedalSTorpSHMyhrG: Ability of navigated 3D ultrasound to delineate gliomas and metastases—comparison of image interpretations with histopathology. Acta Neurochir (Wien)147:1259–12692005
WidhalmGWolfsbergerSMinchevGWoehrerAKrssakMCzechT: 5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Cancer116:1545–15522010
WillemsPWTaphoornMJBurgerHBerkelbach van der SprenkelJWTullekenCA: Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: a randomized controlled trial. J Neurosurg104:360–3682006
WuJSZhouLFTangWJMaoYHuJSongYY: Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in patients with gliomas involving pyramidal tracts. Neurosurgery61:935–9492007