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5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

Valdes, Pablo A. PhD*,‡,§; Bekelis, Kimon MD*; Harris, Brent T. MD, PhD; Wilson, Brian C. PhD; Leblond, Frederic PhD‡,#; Kim, Anthony PhD; Simmons, Nathan E. MD*; Erkmen, Kadir MD*; Paulsen, Keith D. PhD‡,**; Roberts, David W. MD*,§,**

doi: 10.1227/NEU.0000000000000117
Technique Assessment

BACKGROUND: The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX.

OBJECTIVE: To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma.

METHODS: ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities.

RESULTS: Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura.

CONCLUSION: ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

ABBREVIATIONS: ALA, 5-aminolevulinic acid

AUC, area under the curve

FGR, fluorescence-guided resection

NPV, negative predictive value

PpIX, protoporphyrin IX

PPV, positive predictive value

ROC, receiver operating characteristic

WHO, World Health Organization

*Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire;

Thayer School of Engineering, Hanover, New Hampshire;

§Geisel School of Medicine at Dartmouth, Hanover, New Hampshire;

Departments of Pathology and Neurology, Georgetown University Medical Center, Washington, DC;

Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada;

#Engineering Physics Department, École Polytechnique de Montréal, Montreal, Quebec, Canada;

**Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

Correspondence: David W. Roberts, MD, Dartmouth-Hitchcock Medical Center, Section of Neurosurgery, One Medical Center Dr, Lebanon, NH 03756. E-mail: or Pablo A. Valdes, PhD, Dartmouth-Hitchcock Medical Center, Section of Neurosurgery, One Medical Center Dr, Lebanon, NH 03756. E-mail:

Received April 08, 2013

Accepted July 16, 2013

Copyright © by the Congress of Neurological Surgeons