title: Metabolic mapping of gliomas using hybrid MR-PET imaging: feasibility of the method and spatial distribution of metabolic changes.
abstract: OBJECTIVE
  The most powerful adjunct to histopathology for the grading of gliomas seems to be the metabolic imaging using positron emission tomography and magnetic resonance spectroscopy (MRS). The purposes of this study were to examine the feasibility of simultaneous acquisition of both techniques for purposes of tumor grading in a newly launched hybrid magnetic resonance positron emission tomography (MR-PET) and to examine the spatial distributions of metabolic changes in gliomas.
  
  
  METHODS
  Twenty-eight consecutive patients with gliomas underwent simultaneous methionine (Met) MR-PET imaging for detection of the most malignant tumor part before surgical sampling. After coregistration and fusion of MR-PET and MRS data, tumor to normal brain (T/N) Met uptake ratios and the corresponding metabolites peaks (choline [Cho], creatine [Cr], and N-acetylaspartate [NAA]) in MRS were recorded. The patients were divided into 4 types on the basis of the relation between the Met uptake area and the increased metabolite ratios: type I, the increased Met uptake area had at least 50% overlap or was completely within the area of increased Cho/NAA ratio; type II, the increased Met uptake site had less than 50% overlap of increased Cho/NAA ratio site; type III, the increased Met uptake region had no spatial relationship with the "hot" lesions in the MRS maps; and type IV, there was no pathologically increased Met uptake. The surgical sampling was performed in the tumor part with the highest Met uptake and, in the absence of increased Met accumulation, in the site with the highest Cho/NAA ratio. All surgical samples were referred to the neuropathology division for histological grading.
  
  
  RESULTS
  A total of 16 low-grade gliomas (World Health Organization grade II) and 12 high-grade gliomas (World Health Organization grade III) were included. Three lesions (10%) of type I were identified. Four lesions (14%) were classified as type II and 6 lesions (21%) were classified as type 3, where the increased Met uptake region had no spatial relationship with the hot lesions in the MRS maps. In 15 of the 28 patients (54%), there was no increased Met accumulation (type 4 lesions). Maps of Cho/NAA and Cr/NAA showed a close spatial relationship in most of the patients. Median T/N Met uptake ratio in the pooled surgically sampled tumor sites was 1.6 (range, 1-3), and median Cho/NAA and Cho/Cr ratios were 2.1 (range, 0.9-5.8) and 1.5 (range, 0.5-8.3), respectively. Spearman rank correlations of the metabolic markers in the low-grade gliomas showed significant correlations between Met uptake and Cr/NAA ratio (ρ = 0.59; P = 0.015) as well as between Cho/NAA and Cr/NAA ratios (ρ = 0.79; P = 0.0002). The normalized tumor creatine was significantly higher in anaplastic tumors compared with the low-grade gliomas (P = 0.001). A tendency for a significant positive correlation was found between normalized tumor creatine and Met uptake in the anaplastic tumors.
  
  
  CONCLUSIONS
  Metabolic mapping before histological sampling is feasible using simultaneous MR-PET imaging. High T/N Met uptake ratio reflecting high expression of amino-acid membrane transporters, which is indicative of proliferating tumor cell populations, does not always spatially correlate with neuronal cell loss and cell membrane proliferation (Cho/NAA) seen in MRS. Increased Cr/NAA is associated with increased methionine uptake in low-grade gliomas, whereas normalized creatine in tumor tends to correlate with methionine accumulation, which indicates a possible coupling of these metabolic indices in anaplastic tumors. Thus, spatial distribution differences in gliomas should be taken into account when planning surgical sampling.
authors.affiliation: Department of Neuroradiology, Eberhard Karls University, Tübingen, Germany. sotirios.bisdas@med.uni-tuebingen.de
authors.forename: Sotirios
authors.initials: S
authors.lastname: Bisdas
authors.forename: Rainer
authors.initials: R
authors.lastname: Ritz
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bender
authors.forename: Christian
authors.initials: C
authors.lastname: Braun
authors.forename: Christina
authors.initials: C
authors.lastname: Pfannenberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Reimold
authors.forename: Thomas
authors.initials: T
authors.lastname: Naegele
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ernemann
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008715:Methionine; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D008715:Methionine