title: Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker.
abstract: OBJECTIVE
  Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies.
  
  
  METHODS
  The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board-approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo.
  
  
  RESULTS
  A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors.
  
  
  CONCLUSIONS
  These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.
authors: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
authors: Pablo A
authors: PA
authors: Valdés
authors: Frederic
authors: F
authors: Leblond
authors: Anthony
authors: A
authors: Kim
authors: Brent T
authors: BT
authors: Harris
authors: Brian C
authors: BC
authors: Wilson
authors: Xiaoyao
authors: X
authors: Fan
authors: Tor D
authors: TD
authors: Tosteson
authors: Alex
authors: A
authors: Hartov
authors: Songbai
authors: S
authors: Ji
authors: Kadir
authors: K
authors: Erkmen
authors: Nathan E
authors: NE
authors: Simmons
authors: Keith D
authors: KD
authors: Paulsen
authors: David W
authors: DW
authors: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000008:administration & dosage; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D005453:Fluorescence; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008579:Meningioma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX