title: Combination of hand-held probe and microscopy for fluorescence guided surgery in the brain tumor marginal zone.
abstract: BACKGROUND
  Visualization of the tumor is crucial for differentiating malignant tissue from healthy brain during surgery, especially in the tumor marginal zone. The aim of the study was to introduce a fluorescence spectroscopy-based hand-held probe (HHF-probe) for tumor identification in combination with the fluorescence guided resection surgical microscope (FGR-microscope), and evaluate them in terms of diagnostic performance and practical aspects of fluorescence detection.
  
  
  METHODS
  Eighteen operations were performed on 16 patients with suspected high-grade glioma. The HHF-probe and the FGR-microscope were used for detection of protoporphyrin (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) and evaluated against histopathological analysis and visual grading done through the FGR-microscope by the surgeon. A ratio of PpIX fluorescence intensity to the autofluorescence intensity (fluorescence ratio) was used to quantify the spectra detected by the probe.
  
  
  RESULTS
  Fluorescence ratio medians (range 0 - 40) measured by the probe were related to the intensity of the fluorescence in the FGR-microscope, categorized as "none" (0.3, n=131), "weak" (1.6, n=34) and "strong" (5.4, n=28). Of 131 "none" points in the FGR-microscope, 88 (67%) exhibited fluorescence with the HHF-probe. For the tumor marginal zone, the area under the receiver operator characteristics (ROC) curve was 0.49 for the FGR-microscope and 0.65 for the HHF-probe.
  
  
  CONCLUSIONS
  The probe was integrated in the established routine of tumor resection using the FGR-microscope. The HHF-probe was superior to the FGR-microscope in sensitivity; it detected tumor remnants after debulking under the FGR-microscope. The combination of the HHF-probe and the FGR-microscope was beneficial especially in the tumor marginal zone.
authors.affiliation: Department of Biomedical Engineering, Linköping University, Sweden; Department of Neurosurgery Linköping University Hospital, Region Östergötland, Linköping, Sweden. Electronic address: johan.richter@regionostergotland.se.
authors.forename: Johan C O
authors.initials: JCO
authors.lastname: Richter
authors.affiliation: Department of Biomedical Engineering, Linköping University, Sweden.
authors.forename: Neda
authors.initials: N
authors.lastname: Haj-Hosseini
authors.affiliation: Department of Clinical Pathology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Hallbeck
authors.affiliation: Department of Biomedical Engineering, Linköping University, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Wårdell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D006801:Humans; D008297:Male; D000072662:Margins of Excision; D008856:Microscopy, Fluorescence / Q000379:methods*; D008875:Middle Aged; D008904:Miniaturization; D064847:Multimodal Imaging / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000295:instrumentation*; D055815:Young Adult
keywords: 5-Aminolaevulinic acid (5-ALA); Fluorescence guided resection (FGR); Fluorescence spectroscopy; High-grade glioma; Protoporphyrin (PpIX)