Does the expression of glial fibrillary acid protein (GFAP) stain in glioblastoma tissue have a prognostic impact on survival?

OBJECTIVE: Several parameters are known to predict the survival of glioblastoma (GB), including extent of resection and MGMT promotor methylation. Staining for glial fibrillary acidic protein (GFAP) is a common component of routine histological work-up, but its clinical utility in GB is unclear. The aim of the present study was to analyze the predictive value of quantitative GFAP measurements for survival of patients with GB. METHODS: All subjects in our institutional database of patients with primary GB who underwent surgery between 2011 and 2014 with examination of immunohistochemical staining of GFAP were included. Percentage GFAP staining was measured in 5% increments (5-100%). Univariate and multivariate analyses were performed between GFAP values and survival data. Clinically relevant cut-offs for GFAP staining were identified by receiver operating characteristic (ROC) curves. RESULTS: The final cohort consisted of 272GB patients with available quantitative GFAP measurements (mean age, 62 (±11.1) years, 117 females [43%]). Overall survival was 11.4 months (±8.6). Median GFAP value was 70% (range, 5-100%). The ROC curve showed the clinically relevant cut-off for GFAP at 75% (area under the curve: 0.691). Accordingly, GB patients with GFAP≥75% presented poorer survival on Kaplan-Meier survival estimation (P=0.021). Multivariate analysis adjusted for age, extent of resection, preoperative Karnofsky performance status scale, IDH1 mutation and MGMT methylation status confirmed the independent predictive value of GFAP≥75% for overall survival (P=0.032). Finally, patients with GFAP≥75% showed significantly poorer long-term survival than those with GFAP<75%: 5.8% vs. 15.2% (P=0.0183) and 0.8% vs. 8% (P=0.0076) for 2- and 3-year survival, respectively. CONCLUSION: Quantitative immunohistochemical assessment of GFAP staining could provide a novel biomarker for overall and especially long-term survival of patients with GB. Prospective multi-center validation of the prognostic value of GFAP for GB survival is needed.

Wall Contrast Enhancement of Thrombosed Intracranial Aneurysms at 7T MRI.

BACKGROUND AND PURPOSE: The pathophysiology of wall contrast enhancement in thrombosed intracranial aneurysms is incompletely understood. This in vivo study aimed to investigate wall microstructures with gadolinium-enhanced 7T MR imaging. MATERIALS AND METHODS: Thirteen patients with 14 thrombosed intracranial aneurysms were evaluated using a 7T whole-body MR imaging system with nonenhanced and gadolinium-enhanced high-resolution MPRAGE. Tissue samples were available in 5 cases, and histopathologic findings were correlated with 7T MR imaging to identify the gadolinium-enhancing microstructures. RESULTS: Partial or complete inner wall enhancement correlated with neovascularization of the inner wall layer and the adjacent thrombus. Additional partial or complete outer wall enhancement can be explained by formation of vasa vasorum in the outer aneurysm wall layer. The double-rim enhancement correlated with perifocal edema and wall histologic findings suggestive of instability. CONCLUSIONS: Two distinct aneurysm wall microstructures responsible for gadolinium enhancement not depictable at lower spatial resolutions can be visualized in vivo using high-resolution gadolinium-enhanced 7T MR imaging.

Automatic and efficient MRI-US segmentations for improving intraoperative image fusion in image-guided neurosurgery.

Knowledge of the exact tumor location and structures at risk in its vicinity are crucial for neurosurgical interventions. Neuronavigation systems support navigation within the patient's brain, based on preoperative MRI (preMRI). However, increasing tissue deformation during the course of tumor resection reduces navigation accuracy based on preMRI. Intraoperative ultrasound (iUS) is therefore used as real-time intraoperative imaging. Registration of preMRI and iUS remains a challenge due to different or varying contrasts in iUS and preMRI. Here, we present an automatic and efficient segmentation of B-mode US images to support the registration process. The falx cerebri and the tentorium cerebelli were identified as examples for central cerebral structures and their segmentations can serve as guiding frame for multi-modal image registration. Segmentations of the falx and tentorium were performed with an average Dice coefficient of 0.74 and an average Hausdorff distance of 12.2 mm. The subsequent registration incorporates these segmentations and increases accuracy, robustness and speed of the overall registration process compared to purely intensity-based registration. For validation an expert manually located corresponding landmarks. Our approach reduces the initial mean Target Registration Error from 16.9 mm to 3.8 mm using our intensity-based registration and to 2.2 mm with our combined segmentation and registration approach. The intensity-based registration reduced the maximum initial TRE from 19.4 mm to 5.6 mm, with the approach incorporating segmentations this is reduced to 3.0 mm. Mean volumetric intensity-based registration of preMRI and iUS took 40.5 s, including segmentations 12.0 s.

Maleic anhydride proton sponge as a novel MALDI matrix for the visualization of small molecules (<250 m/z) in brain tumors by routine MALDI ToF imaging mass spectrometry.

A novel vacuum stable proton sponge, 4-maleicanhydridoproton sponge (MAPS), was prepared and applied as the matrix in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) of an aggressive brain tumor tissue (glioblastoma multiforme). Ionic maps of lactate, 2-hydroxyglutarate and chloride anions (m/z 89, 147, 35, respectively) were obtained using a routine MALDI ToF mass spectrometer.

Doppler indices of the middle cerebral artery in fetuses with cardiac defects theoretically associated with impaired cerebral oxygen delivery in utero: is there a brain-sparing effect?

OBJECTIVES: To assess changes in the Doppler flow profiles of the middle cerebral artery in fetuses with cardiac defects theoretically associated with impaired cerebral oxygen delivery in utero. METHODS: Z-scores were calculated for pulsatility and resistance indices (PI and RI, respectively) of the middle cerebral artery (MCA) and the cerebroplacental ratio (CPR) between 19 and 41 weeks' gestation, and for head circumference at birth (HC), in 113 fetuses with the following isolated cardiac defects: transposition of the great arteries (TGA; n = 18), hypoplastic left heart (HLH; n = 46), severe aortic stenosis (n = 17), pulmonary atresia (n = 18) and tetralogy of Fallot (TOF; n = 14). Pregnancies with uteroplacental dysfunction (indicated by increased uterine and/or umbilical Doppler indices), growth restriction, extracardiac malformations, chromosomal anomalies as well as multiple pregnancies were excluded to avoid any additional hypoxemic effect as strictly as possible. The results were compared with 1378 normal controls. RESULTS: Fetuses with pulmonary atresia, severe aortic stenosis and TOF had no significant alterations of Doppler parameters or HC at birth. In fetuses with TGA, mean Z-scores of HC at birth were significantly smaller compared with controls (mean +/- SD, -0.73 +/- 1.25; P < 0.05), but there was no significant difference in the Doppler parameters. Fetuses with HLH had significantly lower MCA-PI (-0.57 +/- 0.74; P < 0.05), MCA-RI (-0.73 +/- 0.85; P < 0.05), CPR (-1.44 +/- 1.05; P < 0.05) and HC (-0.50 +/- 1.24; P < 0.05) Z-scores compared with controls. CONCLUSIONS: Fetuses with cardiac defects theoretically associated with markedly impaired cerebral oxygen delivery in utero (TGA and HLH) have smaller HCs at birth. However, only fetuses with HLH have cerebrovascular alterations that are detectable by evaluation of the Doppler indices MCA-PI, MCA-RI and CPR.