title: Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark; Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
authors: Anna
authors: A
authors: Tietze
authors: Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Kim
authors: K
authors: Mouridsen
authors: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Yasmin
authors: Y
authors: Lassen-Ramshad
authors: Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark; Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
authors: Leif
authors: L
authors: Østergaard
mesh_terms: D019540:Area Under Curve; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply* / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D002560:Cerebrovascular Circulation; D005260:Female; D005910:Glioma / Q000098:blood supply* / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D018810:Magnetic Resonance Angiography; D008297:Male; D008833:Microcirculation; D060787:Neoplasm Grading