title: Minispectrometer with handheld probe for 5-ALA based fluorescence-guided surgery of brain tumors: Preliminary study for clinical applications.
abstract: BACKGROUND
  Recently a mini-spectrometer with a handheld probe quantifying 5-aminolevulinic acid (5-ALA) based fluorescence intensity of brain tumors was developped by Kim et al. to improve fluorescence-guided neurosurgery.
  
  
  OBJECTIVE
  To evaluate if this new tool is capable to discriminate nuances of fluorescence intensity of strongly fluorescing tumors (glioblastomas (GBM) and meningiomas (MM)). To study different modes of measurement (touch/no-touch). To determine protoporphyrin IX (PPIX) concentration in tumor tissue as compared to a laboratory spectrometer.
  
  
  METHODS
  The tumor tissue was resected from patients operated in the neurosurgical department of University Hospital Duesseldorf, Germany between 01/2014 and 06/2014. Two spectrometers, one custom-built with a handheld probe ("mini-spectrometer") and one commercial laboratory spectrometer were employed. After calibration they were used to detect and compare fluorescence intensity of human brain tumor samples ex vivo under standardized conditions. The mini-spectrometer was tested at different distances to the tumor. PPIX concentrations of tumor lysates were determined by both spectrometers.
  
  
  RESULTS
  In total n=11 tumors (5 MM and 6 GBM) resulting in 17 tumor biopsies were studied. All GBM showed significant higher fluorescence intensity as compared to MM (Z=-3.123, p=0.001). The fluorescence signal was inversely proportional to the square of the distance (GBM: R2=0.226; F=4.683; p<0.5; MM: R2=0255; F=8.042; p<0.01). The mini-spectrometer recorded fluorescence signals up to 2mm ("no-touch"). Determination of PPIX concentration in tumor by the mini-spectrometer did not differ from a laboratory spectrometer.
  
  
  CONCLUSIONS
  The mini-spectrometer was a very sensitive tool for detection of 5-ALA based fluorescence of human brain tumors. Fluorescence intensity of glioblastoma and meningioma were significantly different. A no-touch mode of measurement was possible. PPIX concentration in tumor tissue could be determined as precisely as with a laboratory spectrometer. In future clinical trials the practicability of using such a tool in vivo has to be further evaluated.
authors.affiliation: Klinik für Neurochirurgie, Universitätsklinikum Duesseldorf, Heinrich-Heine-Universität, Duesseldorf, Germany. Electronic address: cornelius@med.uni-duesseldorf.de.
authors.forename: J F
authors.initials: JF
authors.lastname: Cornelius
authors.affiliation: Klinik für Neurochirurgie, Universitätsklinikum Duesseldorf, Heinrich-Heine-Universität, Duesseldorf, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Placke
authors.affiliation: Klinik für Neurochirurgie, Universitätsklinikum Duesseldorf, Heinrich-Heine-Universität, Duesseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Knipps
authors.affiliation: Klinik für Neurochirurgie, Universitätsklinikum Duesseldorf, Heinrich-Heine-Universität, Duesseldorf, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Fischer
authors.affiliation: Klinik für Neurochirurgie, Universitätsklinikum Duesseldorf, Heinrich-Heine-Universität, Duesseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kamp
authors.affiliation: Klinik für Neurochirurgie, Universitätsklinikum Duesseldorf, Heinrich-Heine-Universität, Duesseldorf, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Steiger
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology / Q000601:surgery*; D005909:Glioblastoma / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008579:Meningioma / Q000473:pathology / Q000601:surgery*; D019635:Neurosurgical Procedures / Q000295:instrumentation*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics; D011524:Protoporphyrins / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence / Q000295:instrumentation*
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; C028025:protoporphyrin IX
keywords: 5-ALA; Fluorescence-guided; Glioblastoma; Meningioma; Metabolic imaging; Spectrometer