title: Finding the anaplastic focus in diffuse gliomas: the value of Gd-DTPA enhanced MRI, FET-PET, and intraoperative, ALA-derived tissue fluorescence.
abstract: OBJECTIVE
  Diffuse gliomas may harbor anaplastic foci which affect prognosis and determine adjuvant therapies. Such foci are not always detected by contrast-enhancement on MRI. Recently, other modalities have been introduced, such as FET-PET for pre-diagnostic imaging and 5-aminolevulinic derived tumor fluorescence for intraoperative identification of malignant glioma tissue. The relationship between these modalities and their value for guiding biopsies during resection has not yet been elucidated in the group of diffuse gliomas.
  
  
  METHODS
  FET-PET was performed in 30 consecutive patients with intracerebral lesions suggestive of diffuse gliomas on MRI with or without areas of contrast-enhancement. Prior to surgery patients were given 5-ALA at a dose of 20mg/kg body weight. Areas of FET uptake with a lesion/brain ratio of 1.6 or more were considered indicators of tumor. FET-PET data were corregistered with MRI data before surgery in order to obtain neuronavigated biopsies during resection, which were collected from FET positive and negative areas, analyzed for tumor fluorescence and correlated to contrast-enhancement on MRI.
  
  
  RESULTS
  13 of 30 tumors were diagnosed as gliomas WHO Grade II, 15 as gliomas WHO Grade III and 2 as gliomas WHO Grade IV. The mean lesion/brain tissue ratio of FET uptake was significantly greater for high-grade than for low-grade gliomas (averages SD 2.323±0.754 vs. 1.453±0.538 p=0.0014). A match of FET-pos/ALA-pos biopsies was found in 70.6% (12/17) of high-grade gliomas (WHO Grade III/IV) but only in 7.7% (1/13) of low grade gliomas. Gd-neg/FET-neg/ALA-neg biopsies yielded a low-grade tumor in 46.2% (6/13). A mismatch between FET uptake and 5-ALA (FET-pos/ALA-neg) was found in 46.2% (6/13) of the low-grade and in 17.6% (3/17) of the high-grade tumors. The combination of FET-PET- and 5-ALA-positivity yielded a sensitivity for identifying high-grade glioma foci of 70.5% and a specificity of 92.3%.
  
  
  CONCLUSIONS
  In low grade gliomas 5-ALA fluorescence is the exception and FET PET is more sensitive. High grade areas in diffuse gliomas with anaplastic foci usually fluoresce, if they are FET PET positive. As a result, FET PET appears valuable for pre-operative identification of anaplastic foci and hot spots are strongly predictive for ALA-derived fluorescence, which highlight anaplastic foci during resection.
authors.affiliation: Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany. Christian.Ewelt@gmx.net
authors.forename: Christian
authors.initials: C
authors.lastname: Ewelt
authors.forename: Frank W
authors.initials: FW
authors.lastname: Floeth
authors.forename: Jörg
authors.initials: J
authors.lastname: Felsberg
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Steiger
authors.forename: Michael
authors.initials: M
authors.lastname: Sabel
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoffels
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
mesh_terms: D000328:Adult; D000622:Aminolevulinic Acid; D001706:Biopsy; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D003287:Contrast Media; D005260:Female; D005453:Fluorescence; D019786:Gadolinium DTPA; D005910:Glioma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D019635:Neurosurgical Procedures; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D025321:Surgery, Computer-Assisted; D014443:Tyrosine / Q000031:analogs & derivatives
chemical_list: D003287:Contrast Media; D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine; D000622:Aminolevulinic Acid; D019786:Gadolinium DTPA