title: Histopathological Insights on Imaging Results of Intraoperative Magnetic Resonance Imaging, 5-Aminolevulinic Acid, and Intraoperative Ultrasound in Glioblastoma Surgery.
abstract: BACKGROUND
  For appropriate use of available intraoperative imaging techniques in glioblastoma (GB) surgery, it is crucial to know the potential of the respective techniques in tumor detection.
  
  
  OBJECTIVE
  To assess histopathological basis of imaging results of intraoperative magnetic resonance imaging (iMRI), 5-aminolevulinic acid (5-ALA), and linear array intraoperative ultrasound (lioUS).
  
  
  METHODS
  We prospectively compared the imaging findings of iMRI, 5-ALA, and lioUS at 99 intraoperative biopsy sites in 33 GB patients during resection control. Histological classification of specimens, tumor load, presence of necrosis, presence of vascular malformations, and O6-methylguanin-DNA methyltransferase (MGMT) promoter state was correlated with imaging findings.
  
  
  RESULTS
  Solid tumor was found in 57%, infiltration zone in 42%, and no tumor in 1% of specimens. However, imaging was negative in iMRI in 49%, using 5-ALA in 17%, and in lioUS in 21%. In positive imaging results, share of solid tumor was highest in 5-ALA (65%) followed by lioUS (60%) and lowest in iMRI (55%). In comparison to 5-ALA, iMRI had a high share of solid tumor in specimens when showing intermediate results. Sensitivity for invasive tumor was higher in 5-ALA (84%) and lioUS (80%) than in iMRI (50%). We found a significant correlation of 5-ALA with classification of specimen, presence of necrosis, and microproliferations. Methylated MGMT promoter correlated with positive findings in 5-ALA. lioUS and iMRI showed no correlations with histopathological findings.
  
  
  CONCLUSIONS
  All of the assessed established imaging techniques detect infiltrating tumor only to a certain extent. Only 5-ALA showed a significant correlation with histopathological findings. Interestingly, tumor remnants in an MGMT-methylated tumor are more likely to be visible using 5-ALA as in unmethylated tumors.
authors.affiliation: Department of Neurosurgery, University of Ulm, Günzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Coburger
authors.affiliation: Section of Neuropathology, University of Ulm, Günzburg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Scheuerle
authors.affiliation: Department of Neurosurgery, University of Ulm, Günzburg, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Pala
authors.affiliation: Research Group Experimental Neurology, Leuven, Belgium.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Thal
authors.affiliation: Department of Neurosurgery, University of Ulm, Günzburg, Germany.
authors.forename: Christian Rainer
authors.initials: CR
authors.lastname: Wirtz
authors.affiliation: Department of Neurosurgery, University of Ulm, Günzburg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: König
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D038361:Neuronavigation; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid