title: Quantitative T1-mapping detects cloudy-enhancing tumor compartments predicting outcome of patients with glioblastoma.
abstract: Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this "cloudy" enhancement during radio-chemotherapy and its impact on patients' progression-free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T-MRI pre- and post contrast agent with standard T1-weighted (T1w) and with sequences to quantify T1 before radiation, and at 6-week intervals during radio-chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy-enhancing compartment and evaluated the impact of their therapy-related volume change upon PFS. In ∆qT1 maps cloudy-enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy-enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P < 0.001). It was located at the margin of solid enhancement which was also seen on T1w. In contrast, the cloudy-enhancing compartment was visually undetectable on ∆T1w. A volume decrease of more than 21.4% of the cloudy-enhancing compartment at first follow-up predicted longer PFS (P = 0.038). Cloudy-enhancing compartment outside the solid contrast-enhancing area of GBM is a new observation which is only visually detectable with qT1-mapping and may represent tumor infiltration. Its early volume decrease predicts a longer PFS in GBM patients during standard radio-chemotherapy.
authors.affiliation: Neuroradiology, Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller
authors.affiliation: Neuroradiology, Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Alina
authors.identifier: 0000-0001-5571-9635
authors.initials: A
authors.lastname: Jurcoane
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Sied
authors.initials: S
authors.lastname: Kebir
authors.affiliation: Neuroradiology, Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Ditter
authors.affiliation: Neuroradiology, Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Schrader
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Herrlinger
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Theophilos
authors.initials: T
authors.lastname: Tzaridis
authors.affiliation: Philips GmbH, UB Healthcare, Lübeckertordamm 5, Hamburg, 20099, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Mädler
authors.affiliation: Neuroradiology, Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Schild
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.|Division of Experimental and Translational Neurooncology, Department of Neurology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.|Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Clinic & University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Glas
authors.affiliation: Neuroradiology, Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, Bonn, 53127, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hattingen
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003287:Contrast Media; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media
keywords: Cloudy-enhancing compartment; T1-mapping; glioblastoma; progression-free survival PFS; quantitative MRI