Increased Delay Between Gadolinium Chelate Administration and T1-Weighted Magnetic Resonance Imaging Acquisition Increases Contrast-Enhancing Tumor Volumes and T1 Intensities in Brain Tumor Patients.

OBJECTIVES: The aim of this study was to evaluate the impact of delayed T1-weighted (T1-w) MRI acquisition after gadolinium chelate administration on brain tumor volumes and T1-w intensities. MATERIALS AND METHODS: Fifty-five patients with histologically confirmed, contrast-enhancing intra-axial brain tumors were analyzed in this prospective test-retest study. Patients underwent 2 consecutive 3 T MRI scans (separated by a 1-minute break) during routine follow-up with contrast-enhanced T1 (ceT1-w), T2, and FLAIR acquisition. Macrocyclic gadolinium chelate-based contrast agent was only administered before the first ceT1-w acquisition; median latency to ceT1-w acquisition was 6.72 minutes (IQR, 6.53-6.92) in the first and 16.27 minutes (IQR, 15.49-17.26) in the second scan. Changes in tumor volumes and relative ceT1-w intensities between the 2 acquisitions were quantitatively assessed following semiautomated tumor segmentation (separately for contrast-enhancement [CE], necrosis [NEC], and nonenhancing [NE] tumor). RESULTS: Semiautomatically segmented CE tumor volumes were significantly larger in the second acquisition (median +32% [1.2 cm]; IQR, 16%-62%; P < 0.01), which corresponded to a 10% increase in CE tumor diameter (+0.3 cm). Contrarily, NEC and NE tumor volumes were significantly smaller (median -24% [IQR, -36% to -54%], P < 0.01 for NEC and -2% [IQR, -1% to -3%], P = 0.02 for NE tumor). Bland-Altman plots confirmed a proportional bias toward higher CE and lower NEC volumes for the second ceT1-w acquisition. Relative ceT1-w intensities for both early- (regions already enhancing in the first scan) and late-enhancing (newly enhancing regions in the second scan) tumor were significantly increased in the second acquisition (by 5.8% and 27.3% [P < 0.01, respectively]). Linear-mixed effects modeling confirmed that the increase in CE volumes and CE intensities is a function of the interval between contrast agent injection and ceT1-w acquisition (P < 0.01 each). CONCLUSIONS: Our study indicates that the maximum extent of CE tumor volumes and intensities may increase beyond the time frame of 4 to 8 minutes after contrast agent injection and potentially affects the diagnosis of progressive or recurrent disease because late-enhancing recurrent disease might not be unequivocally detected on standard follow-up MRI.

Radiomic subtyping improves disease stratification beyond key molecular, clinical, and standard imaging characteristics in patients with glioblastoma.

Background: The purpose of this study was to analyze the potential of radiomics for disease stratification beyond key molecular, clinical, and standard imaging features in patients with glioblastoma. Methods: Quantitative imaging features (n = 1043) were extracted from the multiparametric MRI of 181 patients with newly diagnosed glioblastoma prior to standard-of-care treatment (allocated to a discovery and a validation set, 2:1 ratio). A subset of 386/1043 features were identified as reproducible (in an independent MRI test-retest cohort) and selected for analysis. A penalized Cox model with 10-fold cross-validation (Coxnet) was fitted on the discovery set to construct a radiomic signature for predicting progression-free and overall survival (PFS and OS). The incremental value of a radiomic signature beyond molecular (O6-methylguanine-DNA methyltransferase [MGMT] promoter methylation, DNA methylation subgroups), clinical (patient's age, KPS, extent of resection, adjuvant treatment), and standard imaging parameters (tumor volumes) for stratifying PFS and OS was assessed with multivariate Cox models (performance quantified with prediction error curves). Results: The radiomic signature (constructed from 8/386 features identified through Coxnet) increased the prediction accuracy for PFS and OS (in both discovery and validation sets) beyond the assessed molecular, clinical, and standard imaging parameters (P ≤ 0.01). Prediction errors decreased by 36% for PFS and 37% for OS when adding the radiomic signature (compared with 29% and 27%, respectively, with molecular + clinical features alone). The radiomic signature was-along with MGMT status-the only parameter with independent significance on multivariate analysis (P ≤ 0.01). Conclusions: Our study stresses the role of integrating radiomics into a multilayer decision framework with key molecular and clinical features to improve disease stratification and to potentially advance personalized treatment of patients with glioblastoma.

The pore structure and gating mechanism of K2P channels.

Two-pore domain (K2P) potassium channels are important regulators of cellular electrical excitability. However, the structure of these channels and their gating mechanism, in particular the role of the bundle-crossing gate, are not well understood. Here, we report that quaternary ammonium (QA) ions bind with high-affinity deep within the pore of TREK-1 and have free access to their binding site before channel activation by intracellular pH or pressure. This demonstrates that, unlike most other K(+) channels, the bundle-crossing gate in this K2P channel is constitutively open. Furthermore, we used QA ions to probe the pore structure of TREK-1 by systematic scanning mutagenesis and comparison of these results with different possible structural models. This revealed that the TREK-1 pore most closely resembles the open-state structure of KvAP. We also found that mutations close to the selectivity filter and the nature of the permeant ion profoundly influence TREK-1 channel gating. These results demonstrate that the primary activation mechanisms in TREK-1 reside close to, or within the selectivity filter and do not involve gating at the cytoplasmic bundle crossing.