Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma

PLoS One. 2015 Apr 13;10(4):e0123044. doi: 10.1371/journal.pone.0123044. eCollection 2015.


Objectives: Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome than does the established PWI angiogenesis marker, cerebral blood volume (CBV).

Material and methods: Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and the coefficient of variation (COV), its ratio to blood mean transit time, provide indices of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival was examined by the Cox proportional-hazards regression model, and by survival curves using log-rank tests.

Results: The best prediction of grade (AUC = 0.876; p < 0.05) was achieved by combining knowledge of CBV and CTH in the enhancing tumor and peri-focal edema, and patients with glioblastoma multiforme were identified best by CTH (AUC = 0.763; p<0.001). CTH outperformed CBV and COV in predicting time to progression and survival in all gliomas and in a subgroup consisting of only high-grade gliomas.

Conclusion: Our study confirms the importance of microvascular flow control in tumor growth by demonstrating that determining CTH improves tumor grading and outcome prediction in glioma patients compared to CBV alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Brain / pathology
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy
  • Cerebrovascular Circulation*
  • Female
  • Glioma / blood supply*
  • Glioma / diagnosis*
  • Glioma / mortality
  • Glioma / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Angiography*
  • Male
  • Microcirculation*
  • Neoplasm Grading

Grant support

Support was provided by the Danish Ministry of Science, Technology and Innovation’s University Investment Grant (MINDLab; AT, LØ, KM;; grant number: 902063), “Savværksejer Jeppe Juhls og Hustru Ovita Juhls Mindelegat” (AT, LØ;, and ”Harboefonden” (AT; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.