title: Recurrence of glioblastoma is associated with elevated microvascular transit time heterogeneity and increased hypoxia.
abstract: Dynamic susceptibility contrast (DSC) perfusion MRI provide information about differences in macro- and microvasculature when executed with gradient-echo (GE; sensitive to macrovasculature) and spin-echo (SE; sensitive to microvasculature) contrast. This study investigated whether there are differences between macro- and microvascular transit time heterogeneity (MVTH and µVTH) and tissue oxygen tension (PO2mit) in newly-diagnosed and recurrent glioblastoma. Fifty-seven patients with glioblastoma (25 newly-diagnosed/32 recurrent) were examined with GE- and SE-DSC perfusion sequences, and a quantitative blood-oxygen-level-dependent (qBOLD) approach. Maps of MVTH, µVTH and coefficient of variation (MCOV and µCOV) were calculated from GE- and SE-DSC data, respectively, using an extended flow-diffusion equation. PO2mitmaps were calculated from qBOLD data. Newly-diagnosed and recurrent glioblastoma showed significantly lower ( P ≤ 0.001) µCOV values compared to both normal brain and macrovasculature (MCOV) of the lesions. Recurrent glioblastoma had significantly higher µVTH ( P = 0.014) and µCOV ( P = 0.039) as well as significantly lower PO2mitvalues ( P = 0.008) compared to newly-diagnosed glioblastoma. The macrovasculature, however, showed no significant differences. Our findings provide evidence of microvascular adaption in the disorganized tumor vasculature for retaining the metabolic demands in stress response of therapeutically-uncontrolled glioblastomas. Thus, µVTH and PO2mitmapping gives insight into the tumor microenvironment (vascular and hypoxic niches) responsible for therapy resistance.
authors.affiliation: 1 Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.|2 Institute of Medical Radiology, University Clinic of St. Pölten, St. Pölten, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stadlbauer
authors.affiliation: 3 Center of Functionally Integrative Neuroscience and MIND Lab, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Mouridsen
authors.affiliation: 4 Department of Neuroradiology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Doerfler
authors.affiliation: 3 Center of Functionally Integrative Neuroscience and MIND Lab, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Bo Hansen
authors.affiliation: 5 Department of Neurology, University Clinic of St. Pölten, St. Pölten, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Oberndorfer
authors.affiliation: 1 Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: 1 Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.affiliation: 2 Institute of Medical Radiology, University Clinic of St. Pölten, St. Pölten, Austria.
authors.forename: Gertraud
authors.initials: G
authors.lastname: Heinz
authors.affiliation: 1 Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Roessler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001776:Blood Circulation Time; D001931:Brain Mapping; D001932:Brain Neoplasms / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D005260:Female; D005909:Glioblastoma / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006801:Humans; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D055806:Microvessels / Q000187:drug effects*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010100:Oxygen / Q000097:blood; D055420:Perfusion Imaging; D059016:Tumor Microenvironment
chemical_list: D010100:Oxygen
keywords: Glioblastoma; microvasculature; oxygen-tension; recurrence; transit-time-heterogeneity