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In vivo assessment of tumor heterogeneity in WHO 2016 glioma grades using diffusion kurtosis imaging: Diagnostic performance and improvement of feasibility in routine clinical practice
Authors:J.-M. Hempel  J. Schittenhelm  S. Bisdas  C. Brendle  B. Bender  G. Bier  M. Skardelly  G. Tabatabai  S. Castaneda Vega  U. Ernemann  U. Klose
Affiliation:1. Department of Neuroradiology, Eberhard-Karls University, Tübingen, Germany;2. Department of Pathology and Neuropathology, Institute of Neuropathology, Eberhard-Karls University, Tübingen, Germany;3. Department of Neuroradiology, National Hospital of Neurology and Neurosurgery, University College London Hospitals, London, United Kingdom;4. Department of Neurosurgery, Eberhard-Karls University, Tübingen, Germany;5. Centre of Neurooncology, Comprehensive Cancer Center Tübingen-Stuttgart, Eberhard-Karls University, Tübingen, Germany;6. Department of Preclinical Imaging and Radiopharmacy, Werner-Siemens Imaging Center, Eberhard-Karls University, Tübingen, Germany
Abstract:

Purpose

To assess the diagnostic performance of normalized and non-normalized diffusion kurtosis imaging (DKI) metrics extracted from different tumor volume data for grading glioma according to the integrated approach of the revised 2016 WHO classification.

Materials and methods

Sixty patients with histopathologically confirmed glioma, who provided written informed consent, were retrospectively assessed between 01/2013 and 08/2016 from a prospective trial approved by the local institutional review board. Mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were assessed by two blinded physicians from four different volumes of interest (VOI): whole solid tumor including (VOItu-ed) and excluding perifocal edema (VOItu), infiltrative zone (VOIed), and single slice of solid tumor core (VOIslice). Intra-class correlation coefficient (ICC) was calculated to assess inter-rater agreement. One-way ANOVA was used to compare MK between 2016 CNS WHO tumor grades. Friedman's test compared MK and MD of each VOI. Spearman's correlation coefficient was used to correlate MK with 2016 CNS WHO tumor grades. ROC analysis was performed on MK for significant results.

Results

The MK assessment showed excellent inter-rater agreement for each VOI (ICC, 0.906–0.955). MK was significantly lower in IDHmutant astrocytoma (0.40 ± 0.07), than in 1p/19q-confirmed oligodendroglioma (0.54 ± 0.10, P = 0.001) or IDHwild-type glioblastoma (0.68 ± 0.13, P < 0.001). MK and 2016 WHO tumor grades were strongly and positively correlated (VOItu-ed, r = 0.684; VOItu, r = 0.734; VOIed, r = 0.625; VOIslice, r = 0.698; P < 0.001).

Conclusions

Non-normalized MK values obtained from VOItu and VOIslice showed the best reproducibility and highest diagnostic performance for stratifying glioma according to the integrated approach of the recent 2016 WHO classification.
Keywords:Diffusion kurtosis imaging  Grading  Glioma  Integrated diagnosis  2016 CNS WHO  ROI  VOI  Normalization  NAWM  1p/19q LOH  chromosome 1p/19q loss of heterozygosity  2016 CNS WHO  2016 World Health Organization classification (revised 4th edition) of tumors of the central nervous system  ADC  apparent diffusion coefficient  AKC  apparent excess kurtosis coefficient  ANOVA  one-way analysis of variance  AS  astrocytoma  AS2  diffuse astrocytoma  AS3  anaplastic astrocytoma  ATRX  alpha-thalassemia/mental retardation syndrome X-linked  AUC  area under the curve  DKI  diffusion kurtosis imaging  DTI  diffusion tensor imging  FLAIR  fluid attenuated inversion recovery  GBM  glioblastoma  ICC  intra-class correlation coefficient  IDH1/2  isocitrate-dehydrogenase 1/2 mutation  IDH-mutated  IDH wild type  MD  mean diffusivity  MK  mean kurtosis  MPRAGE  magnetization prepared rapid acquisition gradient echo  1p/19q-confirmed oligodendroglioma  OD2  diffuse oligodendroglioma  OD3  anaplastic oligodendroglioma  ROC  receiver operating characteristic curves  TE  time of echo  TR  time of repetition  VOI  volume of interest
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