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

• Published in: PloS one Vol. 10; no. 4; p. e0123044
• Main Authors: Tietze, Anna, Mouridsen, Kim, Lassen-Ramshad, Yasmin, Østergaard, Leif
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.04.2015; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Area Under Curve; Blood; Blood flow; Blood volume; Brain - pathology; Brain Neoplasms - blood supply; Brain Neoplasms - diagnosis; Brain Neoplasms - mortality; Brain Neoplasms - therapy; Brain tumors; Cerebral blood flow; Cerebrovascular Circulation; Coefficient of variation; Edema; Female; Flow control; Glioblastoma; Glioblastoma multiforme; Glioma; Glioma - blood supply; Glioma - diagnosis; Glioma - mortality; Glioma - therapy; Hazards; Heterogeneity; Humans; Hypoxia; Kaplan-Meier Estimate; Magnetic Resonance Angiography; Magnetic resonance imaging; Male; Microcirculation; Microvasculature; Neoplasm Grading; Oxygen; Patients; Perfusion; Predictions; Rank tests; Regression models; Survival; Transit time; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123044

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). 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. 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. 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.