5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo - PubMed (original) (raw)

5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo

Pablo A Valdes et al. Neurosurgery. 2014 Mar.

Abstract

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.

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Figures

FIGURE 1

FIGURE 1

PpIX fluorescence in meningiomas A to D patient 1, 71-year-old man with a WHO I meningioma. Intraoperative images prior to tumor removal under white light (A) and visual fluorescence mode (B), and following tumor removal under white light (C) and fluorescence mode (D), demonstrate resection of tumor and no remnant amounts of visibly fluorescent tissue E to H, patient 2, 65-year-old woman with an atypical WHO II meningioma Intraoperative view under white light (E) and fluorescence mode (F) on the surface of the tumor capsule, showing no visible fluorescence, and deep to the capsule within the fleshy tumor center under white light (G) and fluorescence mode (H), showing strong visible fluorescence I to N patient 3, 80-year-old man with a WHO I meningioma. Intraoperative view of tumor capsule under white light (I) and fluorescence mode (J), with a probe acquisition at the capsule surface; and corresponding white light (K) and fluorescence images (L) deep to capsule with a probe acquisition in the tumor bulk. Spectral readings at capsule (M) show no significant PpIX levels, and only associated autofluorescence in tissue, whereas N shows significant signal and corresponding high levels of accumulated PpIX in the visually nonfluorescent tumor bulk. PpIX, protoporphyrin IX; WHO, World Health Organization.

FIGURE 2

FIGURE 2

Relationships between quantitative and qualitative fluorescence A scatter plot of specimens showing nonvisible (open circles) and visible (closed circles) fluorescence and their quantitative levels of PpIX separated into normal and tumor tissue, with a significant difference between visible and nonvisibly fluorescent (P < .001) and between normal and tumor tissue (P = . 002). Error bars denote median and interquartile range. Two different cutoffs with either improved specificity (solid line, A) or improved sensitivity (dashed line, B) B ROC curves for qualitative fluorescence (vFl, dotted line) and quantitative fluorescence (qFl, solid line) showed a statistically significant difference in the ROC AUC for quantitative fluorescence (P < .01). Sixteen data points are not shown that fell below < 0.001 µg/mL, with 13/16 histopathologically confirmed as normal dura. AUC, area under the curve; PpIX, protoporphyrin IX; ROC, receiver operating characteristic.

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