, Volume 53, Issue 4, pp 291–302 | Cite as

ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma

  • Martha Nowosielski
  • Wolfgang Recheis
  • Georg Goebel
  • Özgür Güler
  • Gerd Tinkhauser
  • Herwig Kostron
  • Michael Schocke
  • Thaddaeus Gotwald
  • Günther Stockhammer
  • Markus Hutterer
Functional Neuroradiology



The purpose of this study is to evaluate apparent diffusion coefficient (ADC) maps to distinguish anti-vascular and anti-tumor effects in the course of anti-angiogenic treatment of recurrent high-grade gliomas (rHGG) as compared to standard magnetic resonance imaging (MRI).


This retrospective study analyzed ADC maps from diffusion-weighted MRI in 14 rHGG patients during bevacizumab/irinotecan (B/I) therapy. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences and of hyperintense T2 lesions (hT2) were calculated. hT2 were defined as regions of interest (ROI) and registered to corresponding ADC maps (hT2-ADC). Histograms were calculated from hT2-ADC ROIs. Thereafter, histogram asymmetry termed “skewness” was calculated and compared to progression-free survival (PFS) as defined by the Response Assessment Neuro-Oncology (RANO) Working Group criteria.


At 8–12 weeks follow-up, seven (50%) patients showed a partial response, three (21.4%) patients were stable, and four (28.6%) patients progressed according to RANO criteria. hT2-ADC histograms demonstrated statistically significant changes in skewness in relation to PFS at 6 months. Patients with increasing skewness (n = 11) following B/I therapy had significantly shorter PFS than did patients with decreasing or stable skewness values (n = 3, median percentage change in skewness 54% versus −3%, p = 0.04).


In rHGG patients, the change in ADC histogram skewness may be predictive for treatment response early in the course of anti-angiogenic therapy and more sensitive than treatment assessment based solely on RANO criteria.


Recurrent high-grade glioma Anti-angiogenic therapy DWI-MRI ADC histograms Skewness 



We thank Mary Margreiter for the critical reading and helpful comments. M. Nowosielski holds a DOC-FORTE Fellowship from the Austrian Academy of Science at the Department of Neurology, Innsbruck Medical University. Özgür Güler’s work was funded by the Austrian Science Foundation (Project 20604-B13).

Conflict of Interest

We declare that we have no conflict of interest.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Martha Nowosielski
    • 1
  • Wolfgang Recheis
    • 2
  • Georg Goebel
    • 3
  • Özgür Güler
    • 4
  • Gerd Tinkhauser
    • 1
  • Herwig Kostron
    • 5
  • Michael Schocke
    • 2
  • Thaddaeus Gotwald
    • 2
  • Günther Stockhammer
    • 1
  • Markus Hutterer
    • 1
    • 6
  1. 1.Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Department of RadiologyInnsbruck Medical UniversityInnsbruckAustria
  3. 3.Department of Medical Statistics, Informatics and Health EconomicsInnsbruck Medical UniversityInnsbruckAustria
  4. 4.4D Visualization Laboratory, University Clinic of Oto-, Rhino- and LaryngologyInnsbruck Medical UniversityInnsbruckAustria
  5. 5.Department of NeurosurgeryInnsbruck Medical UniversityInnsbruckAustria
  6. 6.Department of NeurologyParacelsus Medical University Salzburg–Christian Doppler HospitalSalzburgAustria

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