Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma

Daniel A. Hamstra, Thomas L. Chenevert, Bradford A. Moffat, Timothy D. Johnson, Charles R. Meyer, Suresh K. Mukherji, Douglas J. Quint, Stephen S. Gebarski, Xiaoying Fan, Christina I. Tsien, Theodore S. Lawrence, Larry Junck, Alnawaz Rehemtulla, Brian D. Ross

Research output: Contribution to journalArticlepeer-review

237 Scopus citations


Diffuse malignant gliomas, the most common type of brain tumor, carry a dire prognosis and are poorly responsive to initial treatment. The response to treatment is typically evaluated by measurements obtained from radiographic images several months after the start of treatment; therefore, an early biomarker of tumor response would be useful for making early treatment decisions and for prognostic information. Thirty-four patients with malignant glioma were examined by diffusion MRI before treatment and 3 weeks later. These images were coregistered, and differences in tumor-water diffusion values were calculated as functional diffusion maps (fDM), which were correlated with the radiographic response, time-to-progression (TTP), and overall survival (OS). Changes in fDM at 3 weeks were closely associated with the radiographic response at 10 weeks. The percentage of the tumor undergoing a significant change in the diffusion of water (VT) was different between patients with progressive disease (PD) vs. stable disease (SD) (P < 0.001). Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter TTP compared with SD (median TTP, 4.3 vs. 7.3 months; P < 0.04). By using fDM, early patient stratification also was correlated with shorter OS in the PD group compared with SD patients (median survival, 8.0 vs. 18.2 months; P < 0.01). On the basis of fDM, tumor assessment provided an early biomarker for response, TTP, and OS in patients with malignant glioma. Further evaluation of this technique is warranted to determine whether it may be useful in the individualization of treatment or evaluation of the response in clinical protocols.

Original languageEnglish (US)
Pages (from-to)16759-16764
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number46
StatePublished - Nov 15 2005
Externally publishedYes


  • Diffusion MRI
  • Human glioma
  • Surrogate marker
  • Treatment assessment

ASJC Scopus subject areas

  • General


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