Journal of Neuro-Oncology

, Volume 102, Issue 1, pp 95–103 | Cite as

Volumetric analysis of functional diffusion maps is a predictive imaging biomarker for cytotoxic and anti-angiogenic treatments in malignant gliomas

  • Benjamin M. Ellingson
  • Mark G. Malkin
  • Scott D. Rand
  • Pete S. LaViolette
  • Jennifer M. Connelly
  • Wade M. Mueller
  • Kathleen M. Schmainda
Clinical Study – Patient Study


Anti-angiogenic agents targeting brain tumor neovasculature may increase progression-free survival in patients with recurrent malignant gliomas. However, when these patients do recur it is not always apparent as an increase in enhancing tumor volume on MRI, which has been the standard of practice for following patients with brain tumors. Therefore alternative methods are needed to evaluate patients treated with these novel therapies. Furthermore, a method that can also provide useful information for the evaluation of conventional therapies would provide an important advantage for general applicability. Diffusion-weighted magnetic resonance imaging (DWI) has the potential to serve as a valuable biomarker for these purposes. In the current study, we explore the prognostic ability of functional diffusion maps (fDMs), which examine voxel-wise changes in the apparent diffusion coefficient (ADC) over time, applied to regions of fluid-attenuated inversion recovery (FLAIR) abnormalities in patients with malignant glioma, treated with either anti-angiogenic or cytotoxic therapies. Results indicate that the rate of change in fDMs is an early predictor of tumor progression, time to progression and overall survival for both treatments, suggesting the application of fDMs in FLAIR abnormal regions may be a significant advance in brain tumor biomarker technology.


Functional diffusion map (fDM) Diffusion MRI Glioma Bevacizumab Chemotherapy Angiogenesis Brain tumor 



This work was financially supported by NIH/NCI R21-CA109820, NIH/NCI R01-CA082500, MCW Advancing Healthier Wisconsin/Translational Brain Tumor Research Program, and MCW Cancer Center Fellowship.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Benjamin M. Ellingson
    • 1
    • 2
    • 4
  • Mark G. Malkin
    • 1
    • 3
    • 4
  • Scott D. Rand
    • 1
    • 2
  • Pete S. LaViolette
    • 1
    • 5
  • Jennifer M. Connelly
    • 1
    • 3
  • Wade M. Mueller
    • 1
    • 4
  • Kathleen M. Schmainda
    • 1
    • 2
    • 5
  1. 1.Translational Brain Tumor Research ProgramMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of RadiologyMedical College of WisconsinMilwaukeeUSA
  3. 3.Department of NeurologyMedical College of WisconsinMilwaukeeUSA
  4. 4.Department of NeurosurgeryMedical College of WisconsinMilwaukeeUSA
  5. 5.Department of BiophysicsMedical College of WisconsinMilwaukeeUSA

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