Journal
NEURO-ONCOLOGY
Volume 13, Issue 8, Pages 846-856Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/nor086
Keywords
delta-aminolevulinic acid; fluorescence-guided resection; malignant glioma; proliferation index; protoporphyrin IX
Categories
Funding
- National Institutes of Health by National Institute of Neurological Disorders and Stroke [R01NS052274-01A2]
- National Institutes of Health [R01NS052274-01A2]
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Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of delta-aminolevulinic acid-induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (C-PpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of C-PpIX and tissue proliferation. C-PpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of C-PpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (similar to 40%) that were not visibly fluorescent under the operating microscope had levels of C-PpIX greater than 0.1 mu g/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery.
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