Comparative analysis of molecular and histological glioblastomas: insights into prognostic variance.

PURPOSE: Whether molecular glioblastomas (GBMs) identify with a similar dismal prognosis as a "classical" histological GBM is controversial. This study aimed to compare the clinical, molecular, imaging, surgical factors, and prognosis between molecular GBMs and histological GBMs. METHODS: Retrospective chart and imaging review was performed in 983 IDH-wildtype GBM patients (52 molecular GBMs and 931 histological GBMs) from a single institution between 2005 and 2023. Propensity score-matched analysis was additionally performed to adjust for differences in baseline variables between molecular GBMs and histological GBMs. RESULTS: Molecular GBM patients were substantially younger (58.1 vs. 62.4, P = 0.014) with higher rate of TERTp mutation (84.6% vs. 50.3%, P < 0.001) compared with histological GBM patients. Imaging showed higher incidence of gliomatosis cerebri pattern (32.7% vs. 9.2%, P < 0.001) in molecular GBM compared with histological GBM, which resulted in lesser extent of resection (P < 0.001) in these patients. The survival was significantly better in molecular GBM compared to histological GBM (median OS 30.2 vs. 18.4 months, P = 0.001). The superior outcome was confirmed in propensity score analyses by matching histological GBM to molecular GBM (P < 0.001). CONCLUSION: There are distinct clinical, molecular, and imaging differences between molecular GBMs and histological GBMs. Our results suggest that molecular GBMs have a more favorable prognosis than histological GBMs.

Identification of prognostic imaging biomarkers in H3 K27-altered diffuse midline gliomas in adults: impact of tumor oxygenation imaging biomarkers on survival.

PURPOSE: To investigate prognostic markers for H3 K27-altered diffuse midline gliomas (DMGs) in adults with clinical, qualitative and quantitative imaging phenotypes, including tumor oxygenation characteristics. METHODS: Retrospective chart and imaging reviews were conducted on 32 adults with H3 K27-altered DMGs between 2017 and 2023. Clinical and qualitative imaging characteristics were analyzed. Quantitative imaging assessment was performed from the tumor mask via automatic segmentation to calculate normalized cerebral blood volume (nCBV), capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), relative cerebral metabolic rate of oxygen (rCMRO2), and mean ADC values. Leptomeningeal metastases (LM) was diagnosed with imaging. Cox analyses were conducted to determine predictors of overall survival (OS) in entire patients and a subgroup of patients with contrast-enhancing (CE) tumor. RESULTS: The median patient age was 40.5 years (range 19.9-75.7), with an OS of 30.3 months (interquartile range 11.3-32.3). In entire patients, the presence of LM was the only independent predictor of OS (hazard ratio [HR] = 6.01, P = 0.009). In the subgroup of 23 (71.9%) patients with CE tumors, rCMRO2 of CE tumor (HR = 1.08, P = 0.019) and the presence of LM (HR = 5.92, P = 0.043) were independent predictors of OS. CONCLUSION: The presence of LM was independently associated with poor prognosis in adult patients with H3 K27-altered DMG. In patients with CE tumors, higher rCMRO2 of CE tumor, which may reflect higher metabolic activity in the tumor oxygenation microenvironment, may be a useful imaging biomarker to predict poor prognosis.

Leptomeningeal Metastases in IDH-wildtype Glioblastomas Revisited: Comprehensive Analysis of Incidence, Risk Factors, and Prognosis Based on Post-contrast FLAIR.

BACKGROUND: The incidence of leptomeningeal metastases (LM) has been reported diversely. This study aimed to investigate the incidence, risk factors, and prognosis of LM in patients with IDH-wildtype glioblastoma. METHODS: A total of 828 patients with IDH-wildtype glioblastoma were enrolled between 2005 and 2022. Baseline preoperative MRI including post-contrast fluid-attenuated inversion recovery (FLAIR) was used for LM diagnosis. Qualitative and quantitative features, including distance between tumor and subventricular zone (SVZ) and tumor volume by automatic segmentation of the lateral ventricles and tumor, were assessed. Logistic analysis of LM development was performed using clinical, molecular, and imaging data. Survival analysis was performed. RESULTS: The incidence of LM was 11.4%. MGMTp unmethylation (odds ratio [OR] = 1.92, P = 0.014), shorter distance between tumor and SVZ (OR = 0.94, P = 0.010), and larger contrast-enhancing tumor volume (OR = 1.02, P < 0.001) were significantly associated with LM. The overall survival (OS) was significantly shorter in patients with LM than in those without (log-rank test; P < 0.001), with median OS of 12.2 and 18.5 months, respectively. Presence of LM remained an independent prognostic factor for OS in IDH-wildtype glioblastoma (hazard ratio = 1.42, P = 0.011), along with other clinical, molecular, imaging, and surgical prognostic factors. CONCLUSION: The incidence of LM is high in patients with IDH-wildtype glioblastoma, and aggressive molecular and imaging factors are correlated with LM development. The prognostic significance of LM based on post-contrast FLAIR imaging suggests acknowledgement of post-contrast FLAIR as a reliable diagnostic tool for clinicians.

Development of Magnetic Resonance-Compatible Head Immobilization Device and Initial Experience of Magnetic Resonance-Guided Radiation Therapy for Central Nervous System Tumors.

PURPOSE: We aimed to develop and investigate positional reproducibility using a fixation device (Unity Brain tumor Immobilization Device [UBID]) in patients with brain tumor undergoing magnetic resonance (MR)-guided radiation therapy (RT) with a 1.5 Tesla (T) MR-linear accelerator (MR-LINAC) to evaluate its feasibility in clinical practice and report representative cases of patients with central nervous system (CNS) tumor. MATERIALS AND METHODS: Quantitative analysis was performed by comparing images obtained by placing only the MR phantom on the couch with those obtained by placing UBID next to the MR phantom. Twenty patients who underwent RT for CNS tumors using 1.5T MR-LINAC between June and October 2022 were retrospectively analyzed. Among them, 5 did not use UBID, whereas 15 used UBID. The positional reproducibility of UBID was evaluated using the median interfractional and intrafractional errors in the first 10 fractions. RESULTS: Each MR quality factor of the MR phantom with UBID satisfied the criteria presented by Elekta. Median values of median shifts in the mediolateral, anteroposterior, and craniocaudal axes for interfractional errors were 2.98, 2.35, and 1.40 mm, respectively. For intrafractional errors, the median values were 0.05, 0.03, and 0.06 mm, respectively. The median values of the median rotations in pitch, roll, and yaw for both interfractional and intrafractional rotations were 0.00°. One patient diagnosed with an optic nerve sheath meningioma received RT with motion monitoring during irradiation. In 2 patients, changes in the tumor cavity and residual lesions were observed in the MRI obtained using 1.5T MR-LINAC on the day of the first treatment and immediately before the 21st fraction, respectively; therefore, offline/online adaptation was performed. CONCLUSIONS: The reproducible and immobile UBID is clinically feasible in patients with CNS tumors receiving RT with 1.5T MR-LINAC. Based on our initial experience, we developed a workflow for 1.5T MR-LINAC treatment of CNS tumors.

Magnetic Resonance Imaging-Based Radiomics for the Prediction of Progression-Free Survival in Patients with Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Advanced non-metastatic nasopharyngeal carcinoma (NPC) has variable treatment outcomes. However, there are no prognostic biomarkers for identifying high-risk patients with NPC. The aim of this systematic review and meta-analysis was to comprehensively assess the prognostic value of magnetic resonance imaging (MRI)-based radiomics for untreated NPC. The PubMed-Medline and EMBASE databases were searched for relevant articles published up to 12 August 2021. The Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) checklist was used to determine the qualities of the selected studies. Random-effects modeling was used to calculate the pooled estimates of Harrell's concordance index (C-index) for progression-free survival (PFS). Between-study heterogeneity was evaluated using Higgins' inconsistency index (I2). Among the studies reported in the 57 articles screened, 10 with 3458 patients were eligible for qualitative and quantitative data syntheses. The mean adherence rate to the TRIPOD checklist was 68.6 ± 7.1%. The pooled estimate of the C-index was 0.762 (95% confidence interval, 0.687-0.837). Substantial between-study heterogeneity was observed (I2 = 89.2%). Overall, MRI-based radiomics shows good prognostic performance in predicting the PFS of patients with untreated NPC. However, more consistent and robust study protocols are necessary to validate the prognostic role of radiomics for NPC.

Low-Dose Three-Dimensional Rotational Angiography for Evaluating Intracranial Aneurysms: Analysis of Image Quality and Radiation Dose.

OBJECTIVE: This study aimed to evaluate the image quality and dose reduction of low-dose three-dimensional (3D) rotational angiography (RA) for evaluating intracranial aneurysms. MATERIALS AND METHODS: We retrospectively evaluated the clinical data and 3D RA datasets obtained from 146 prospectively registered patients (male:female, 46:100; median age, 58 years; range, 19-81 years). The subjective image quality of 79 examinations obtained from a conventional method and 67 examinations obtained from a low-dose (5-seconds and 0.10-µGy/frame) method was assessed by two neurointerventionists using a 3-point scale for four evaluation criteria. The total image quality score was then obtained as the average of the four scores. The image quality scores were compared between the two methods using a noninferiority statistical testing, with a margin of -0.2 (i.e., score of low-dose group - score of conventional group). For the evaluation of dose reduction, dose-area product (DAP) and air kerma (AK) were analyzed and compared between the two groups. RESULTS: The mean total image quality score ± standard deviation of the 3D RA was 2.97 ± 0.17 by reader 1 and 2.95 ± 0.20 by reader 2 for conventional group and 2.92 ± 0.30 and 2.95 ± 0.22, respectively, for low-dose group. The image quality of the 3D RA in the low-dose group was not inferior to that of the conventional group according to the total image quality score as well as individual scores for the four criteria in both readers. The mean DAP and AK per rotation were 5.87 Gy-cm² and 0.56 Gy, respectively, in the conventional group, and 1.32 Gy-cm² (p < 0.001) and 0.17 Gy (p < 0.001), respectively, in the low-dose group. CONCLUSION: Low-dose 3D RA was not inferior in image quality and reduced the radiation dose by 70%-77% compared to the conventional 3D RA in evaluating intracranial aneurysms.

Preoperative assessment of cervical lymph node metastases in patients with papillary thyroid carcinoma: Incremental diagnostic value of dual-energy CT combined with ultrasound.

PURPOSE: To determine whether dual-energy CT (DECT) has incremental diagnostic value when combined with ultrasound (US) in the diagnosis of metastatic cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). METHODS: This was a single-center retrospective cohort study of patients diagnosed with PTC between October 2019 and August 2020. US features of LNs to include hyperechogenicity, round shape, microcalcification, cystic component, and homogeneous/peripheral vascularity were considered suggestive of metastasis. The HU of arterial phase (HUarterial) and DECT-derived CT images [contrast media (CM) and areas under the 100 keV monoenergetic curve (AUC100keV)] were measured. Effective atomic numbers (Zeff), iodine concentration (mg/mL), and slope of the HU curve (λHU) were also obtained. The values for metastatic and benign LNs were compared using Student's t-test with false-discovery correction. Logistic regression with areas under the receiver operating characteristic curves (AUCs) were performed for predicting metastatic LNs. RESULTS: A total of 102 patients were included (49 metastatic and 53 benign LNs; mean age, 46±15 years). Metastatic LNs showed significantly higher values for HUarterial, CM, Zeff, λHU, AUC100keV, and iodine concentration (all, P = 0.001). In logistic regression, the HUarterial demonstrated the highest AUC (0.824; 95% confidence interval [CI], 0.751-0.897), followed by CM HU (0.762; 95% CI, 0.679-0.846). Combination of DECT parameters with US features improved the AUC from 0.890 to 0.941. CONCLUSION: Compared to US features alone, combination with DECT-derived quantitative parameters improved diagnostic performance in predicting metastatic cervical LNs in patients with PTC.

Comparison of early F-18 Florbetaben PET/CT to Tc-99m ECD SPECT using voxel, regional, and network analysis.

This study aimed to validate early-phase F-18 Florbetaben positron emission tomography (eFBB PET) as a brain perfusion test and determine the optimal reference region. A total of 27 patients with early Parkinson's disease with Tc-99m ethyl cysteinate dimer single photon emission tomography (ECD SPECT) and FBB PET were included. Six reference regions, including whole brain (GN), pons, central white matter (CWM), whole cerebellum (WC), WC with brain stem (WC + B), and cerebellar grey matter (CG), were applied to obtain SUVR using cortex volume-of-interest (VOI). Reference regions of WC (r 0.886), WC + B (r 0.897), and CG (r 0.904) had highest correlation values of cortex-VOI SUVR between both perfusion images (all p < 0.001). Early-phase FBB PET had a significant linear correlation of CG-normalized SUVR of the cortex, basal ganglia, thalamus, and midbrain with ECD SPECT in voxel-wise analysis (FDR adjusted-p < 0.05). Early-phase FBB PET extracts more ICNS than ECD SPECT, as 9 ICNS and 4 ICNs, respectively. Both eFBB PET and ECD SPECT well discriminated PD from DLB (Area-under-curve of receiver-operating-characteristics, 0.911 for eFBB PET, 0.922 for ECD SPECT). Our findings suggest that eFBB PET is a reliable perfusion test based on a high correlation with ECD SPECT using cerebellum-based normalization methods.

Radiomics may increase the prognostic value for survival in glioblastoma patients when combined with conventional clinical and genetic prognostic models.

OBJECTIVES: To evaluate the additional prognostic value of multiparametric MR-based radiomics in patients with glioblastoma when combined with conventional clinical and genetic prognostic factors. METHODS: In this single-center study, patients diagnosed with glioblastoma between October 2007 and December 2019 were retrospectively screened and grouped into training and test sets with a 7:3 distribution. Segmentations of glioblastoma using multiparametric MRI were performed automatically via a convolutional-neural network. Prognostic factors in the clinical model included age, sex, type of surgery/post-operative treatment, and tumor location; those in the genetic model included statuses of isocitrate dehydrogenase-1 mutation and O-6-methylguanine-DNA-methyltransferase promoter methylation. Univariate and multivariate Cox proportional hazards analyses were performed for overall survival (OS) and progression-free survival (PFS). Integrated time-dependent area under the curve (iAUC) for survival was calculated and compared between prognostic models via the bootstrapping method (performances were validated with prediction error curves). RESULTS: Overall, 120 patients were included (training set, 85; test set, 35). The mean OS and PFS were 25.5 and 18.6 months, respectively. The prognostic performances of multivariate models improved when radiomics was added to the clinical model (iAUC: OS, 0.62 to 0.73; PFS, 0.58 to 0.66), genetic model (iAUC: OS, 0.59 to 0.67; PFS, 0.59 to 0.65), and combined model (iAUC: OS, 0.65 to 0.73; PFS, 0.62 to 0.67). In the test set, the combined model (clinical, genetic, and radiomics) demonstrated robust validation for risk prediction of OS and PFS. CONCLUSIONS: Radiomics increased the prognostic value when combined with conventional clinical and genetic prognostic models for OS and PFS in glioblastoma patients. KEY POINTS: • CNN-based automatic segmentation of glioblastoma on multiparametric MRI was useful in extracting radiomic features. • Patients with glioblastoma with high-risk radiomics scores had poor overall survival (hazards ratio 8.33, p < 0.001) and progression-free survival (hazards ratio 3.76, p < 0.001). • MR-based radiomics improved the survival prediction when combined with clinical and genetic factors (overall and progression-free survival iAUC from 0.65 to 0.73 and 0.62 to 0.67, respectively; both p < 0.001).

MRI and Quantitative Magnetic Susceptibility Maps of the Brain after Serial Administration of Gadobutrol: A Longitudinal Follow-up Study.

Background The relationship between administration of macrocyclic gadolinium-based contrast agents and T1-weighted signal intensity (SI) change of the globus pallidus (GP) and dentate nucleus (DN) is, to the knowledge of the authors, not known. Purpose To determine if quantitative susceptibility mapping (QSM) can detect changes in magnetic susceptibility of the GP and DN after serial administration of macrocyclic gadobutrol in patients with primary brain tumors. Materials and Methods Patients diagnosed with primary brain tumors from August 2014 to February 2019 were eligible for this single-center retrospective study. Among 501 consecutive adult patients who were given at least one administration of gadobutrol, those who were previously administered an unknown or linear gadolinium-based contrast agent were excluded. Brain MRI scans with three-dimensional gradient-recalled-echo image phase data for QSM processing were reviewed. Regions of interest were drawn on the GP and DN on the basis of semiautomatic thresholding. Univariable generalized estimation equations were used to determine the associations between MRI measures (SI on T1-weighted images and magnetic susceptibility on QSM) and number of gadobutrol doses. Potential confounding factors were adjusted for in multivariable generalized estimating equation. Results Ninety patients (mean age, 51 years ± 17 [standard deviation]; 51 men) with 199 MRI scans were analyzed. In models adjusted for repeated observations between injections, the number of injections of gadobutrol was associated with the magnetic susceptibility of the GP (1.4 × 10-3 ppm/number of gadobutrol injections; P = .01) and DN (8.1 × 10-4 ppm/number of gadobutrol injections; P = .03). After adjustment for confounders, the number of gadobutrol injections remained an independent predictor of increased magnetic susceptibility in the GP (1.3 × 10-3 ppm/number of gadobutrol injections; 95% confidence interval: 0.39 × 10-3, -2.4 × 10-3; P = .006). There were no associations between number of gadobutrol injections and SI or magnetic susceptibility in the DN. Conclusion The magnetic susceptibility of the globus pallidus increased after serial administration of gadobutrol. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Wang and Prince in this issue.

Prognostic value of computed tomography-based volumetric body composition analysis in patients with head and neck cancer: Feasibility study.

BACKGROUND: This study aimed to evaluate whether computed tomography (CT)-based volumetric body composition analysis has prognostic value in head and neck cancer (HNC) patients. METHODS: This single-center retrospective study included 79 patients with HNC treated with definitive radiotherapy from March 2009 to December 2018. The patients were assessed for (a) weight-based variables and (b) pretreatment and posttreatment CT-based body composition variables. Overall survival (OS) and recurrence-free survival (RFS) analyses were conducted using Cox proportional hazards analyses. RESULTS: Depletion of cervical skeletal muscle volume on presentation was associated with poor OS (hazard ratio [HR] = 3.1; 95% CI = 1.2-7.8; P = .016). Low fat proportions before and after treatment were associated with poor OS (HR = 2.5-3.5; 95% CI = 1.3-9.3; P = .013-.026). In multivariate Cox analysis, increased posttreatment fat attenuation demonstrated the greatest prognostic value for both OS (HR = 4.7; 95% CI = 2.2-10.3; P < .001) and RFS (HR = 4.3; 95% CI = 2.0-9.5; P < .001). CONCLUSIONS: CT-based body composition analysis has the potential for risk assessment in patients with HNC.

IDH1 mutation prediction using MR-based radiomics in glioblastoma: comparison between manual and fully automated deep learning-based approach of tumor segmentation.

PURPOSE: This study aimed to determine whether MR-based radiomics of glioblastoma can predict the isocitrate dehydrogenase-1 (IDH1) mutation status and compare predictive performances between manual and fully automatic deep-learning segmentations. METHOD: Forty-five glioblastoma patients with pretreatment T2-weighted MRIs were retrospectively evaluated. Manual segmentations of glioblastoma and peri-tumoral edema were trained via a deep neural network (V-Net). An independent external cohort of 137 glioblastoma patients from the Cancer Imaging Archive was also included (test set 1, n = 46; test set 2, n = 91). Test set 1-without known IDH1 status-was used to calculate dice similarity coefficients (DSC) between the two segmentation methods (manual & V-Net). From test set 2, all-relevant radiomic features were selected via a random forest-based wrapper algorithm for IDH1 prediction. Receiver operating characteristics (ROC) curves with areas under the curve (AUC) were plotted as performance metrics for both methods. RESULTS: Among 136 patients (45 and 91 patients from our institution and test set 2, respectively), 17 patients (11.2 %) had IDH1 mutations. The mean DSC of test set 1 was 0.78 ±â€¯0.14 (range, 0.34-0.94). A subset of 9 all-relevant features (8.4 %, 9/107) was selected. V-Net segmentation of the test set 2 yielded similar performance in predicting IDH1 mutation as compared to manual segmentation (V-Net AUC = 0.86 vs. manual AUC = 0.90). The optimal cut-point threshold of AUC yielded 86.8 % accuracy for manual segmentation and 75.8 % for V-Net segmentation. CONCLUSIONS: V-Net showed robust segmentation capability of glioblastoma on T2-weighted MRI. All-relevant radiomics features from both segmentation methods yielded a similar performance in IDH1 prediction.

Endogenous TLR2 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1.

BACKGROUND: The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands of Toll-like receptors (TLRs) have been suggested to activate adaptive immune responses by modulating the function of antigen-presenting cells (APCs). Despite their therapeutic potential, the development of TLR ligands for immunotherapy is often hampered due to rapid systemic toxicity. Regarding the safety concerns of currently available TLR ligands, finding a new TLR agonist with potent efficacy and safety is needed. METHODS: A unique structural domain (UNE-C1) was identified as a novel TLR2/6 in the catalytic region of human cysteinyl-tRNA synthetase 1 (CARS1) using comprehensive approaches, including RNA sequencing, the human embryonic kidney (HEK)-TLR Blue system, pull-down, and ELISA. The potency of its immunoadjuvant properties was analyzed by assessing antigen-specific antibody and CTL responses. In addition, the efficacy of tumor growth inhibition and the presence of the tumor-infiltrating leukocytes were evaluated using E.G7-OVA and TC-1 mouse models. The combined effect of UNE-C1 with an immune checkpoint inhibitor, anti-CTLA-4 antibody, was also evaluated in vivo. The safety of UNE-C1 immunization was determined by monitoring splenomegaly and cytokine production in the blood. RESULTS: Here, we report that CARS1 can be secreted from cancer cells to activate immune responses via specific interactions with TLR2/6 of APCs. A unique domain (UNE-C1) inserted into the catalytic region of CARS1 was determined to activate dendritic cells, leading to the stimulation of robust humoral and cellular immune responses in vivo. UNE-C1 also showed synergistic efficacy with cancer antigens and checkpoint inhibitors against different cancer models in vivo. Further, the safety assessment of UNE-C1 showed lower systemic cytokine levels than other known TLR agonists. CONCLUSIONS: We identified the endogenous TLR2/6 activating domain from human cysteinyl-tRNA synthetase CARS1. This novel TLR2/6 ligand showed potent immune-stimulating activity with little toxicity. Thus, the UNE-C1 domain can be developed as an effective immunoadjuvant with checkpoint inhibitors or cancer antigens to boost antitumor immunity.

CT-based quantitative evaluation of the efficacy after radiofrequency ablation in patients with benign thyroid nodules.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of CT for quantitative assessment of the neck structures after RFA in patients with benign thyroid nodules. MATERIALS AND METHODS: This single-center, retrospective cohort study included 38 patients with benign thyroid nodules who had received RFA and had available pre- and post-treatment CT images. Changes in the tracheal anteroposterior (AP)/transverse diameter ratio, cross-sectional tracheal area, midline deviation of the trachea, and anterior neck angle after RFA were quantitatively measured using CT. Volume reduction rates (VRRs) for the thyroid gland and nodules were measured using CT and US, respectively, and the intraclass correlation coefficient (ICC) was calculated. The paired Wilcoxon signed-rank test was used to compare pre- and post-treatment CT-based measurements, and univariate linear regression analysis was performed to determine the association of VRR with the mean delivered radiofrequency energy, number of RFA sessions, and initial thyroid volume. RESULTS: After RFA, the tracheal AP/transverse diameter ratio and midline deviation were significantly decreased while the tracheal area and anterior neck angle were significantly increased (all, p < 0.001). The thyroid volume reduction was also significant (VRR, 42.1% ± 21.1%, p < 0.001), with moderate consistency between the CT-based thyroid VRR and US-based nodule VRR (ICC = 0.68, 95% confidence interval = 0.38-0.83, p < 0.001). The mean delivered radiofrequency energy (p = 0.565), number of RFA sessions (p = 0.209), and initial thyroid volume (p = 0.363) showed no significant association with VRR. CONCLUSION: CT-based quantitative assessments may be useful for evaluating improvements in the neck structures after RFA for benign thyroid nodules.

Analysis of heterogeneity of peritumoral T2 hyperintensity in patients with pretreatment glioblastoma: Prognostic value of MRI-based radiomics.

PURPOSE: On MR imaging, peritumoral T2 hyperintensity surrounding glioblastoma is known to contain tumor cell infiltrates, thus contributing to poor prognosis. This study aimed to determine the incremental prognostic value of radiomics on peritumoral T2 hyperintensity in pretreatment glioblastoma. METHODS: One hundred fourteen pathologically confirmed glioblastoma patients were retrospectively selected from March 2008 to May 2018 (our institution, n = 61; the Cancer Imaging Archive, n = 53). All patients were randomly divided into either training (n = 80) or test set (n = 34). Manually segmented peritumoral T2 hyperintensity yielded 106 radiomic features per patient. A random forest variable selection was used to select the most relevant radiomic features. Four Cox proportional hazards models were fitted with clinical features, clinical features with tumor/peritumoral volumes, radiomics, and all of them combined. Kaplan-Meier survival curves of the models were plotted with log-rank tests. All models were validated on a test set using prediction error curves over survival times. RESULTS: A random forest variable selection yielded five relevant features among the 106 radiomic features (two shape, two gray-level and one first order features). These radiomic features increased survival prediction accuracy when they were added onto clinical and tumor/peritumoral volumetric features (combined model, P = 0.011). On test set, the combined model showed lower mean survival prediction error rate (0.14) than clinical (0.191) or radiomic (0.178) model. CONCLUSIONS: The clinical model with radiomic features demonstrated improved survival predictive performance than the model without radiomic features, thus suggesting incremental prognostic value of peritumoral radiomics as MR imaging biomarker in pretreatment glioblastoma.

Analysis of peritumoral hyperintensity on pre-operative T2-weighted MR images in glioblastoma: Additive prognostic value of Minkowski functionals.

OBJECTIVES: The extent of peritumoral tumor cell infiltrations in glioblastoma contributes to poor prognosis. We aimed to assess additive prognostic value of Minkowski functionals in analyzing heterogeneity of peritumoral hyperintensity on T2WI in glioblastoma patients. METHODS: Clinical data (age, sex, extent of surgical resection), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and pre-operative T2WI of 113 pathologically confirmed glioblastoma patients (from our institution, n = 61; from the Cancer Imaging Archive, n = 52) were retrospectively reviewed. The patients were randomly grouped into a training set (n = 80) and a test set (n = 33). Peritumoral T2 hyperintensity was manually segmented and Minkowski functionals-a texture analysis method capturing heterogeneity of MR images-were computed as a function of 11 grayscale thresholds. The Cox proportional hazards models were fitted with clinical variables, Minkowski functionals features as well as both combined. The risk prediction performances of the Minkowski functionals and combined models were validated on a separate test dataset. The sex-specific survival difference of the entire cohort was analyzed according to MGMT methylation status via Kaplan-Meier survival curves. RESULTS: Thirty-three Minkowski features (11 area, 11 perimeter and 11 genus) for each patient were acquired giving a total of 3729 features. Cox regression models fitted with clinical data, Minkowski features, and both combined had incremental concordance indices of 0.577 (P = 0.02), 0.706 (P = 0.02) and 0.714 (P = 0.01) respectively. The prediction error rate of the combined model-having clinical and Minkowski features-was lower than that of Minkowski functionals model (0.135 and 0.161, respectively) when validated on a test dataset. No sex-specific survival difference was found according to MGMT methylation status (male, P = 0.2; female, P = 0.22). CONCLUSIONS: Minkowski functionals features computed from peritumoral hyperintensity can capture heterogeneity of glioblastoma on T2WI and have additive prognostic value in predicting survival, demonstrating their potential in complementing currently available prognostic parameters.

Relationships among stress, emotional intelligence, cognitive intelligence, and cytokines.

The brain has multiple functions, and its structures are very closely related to one another. Thus, the brain areas associated with stress, emotion, and intelligence are closely connected. The purpose of this study was to investigate the multiple associations between stress and emotional intelligence (EI), between EI and intelligence quotient (IQ), between cytokines and stress, and between cytokines and IQ. We measured the stress, EI, cognitive intelligence using IQ, and cytokine levels of 70 healthy subjects. We also analyzed the association of cytokines with IQ according to hemispheric dominance using the brain preference indicator (BPI). We found significant negative correlations between stress and the components of EI, such as emotional awareness and expression, emotional thinking, and emotional regulation. High levels of anger, which is a component of stress, were significantly related to poor emotional regulation. Additionally, emotional application was positively correlated with full-scale IQ scores and scores on the vocabulary, picture arrangement, and block design subtests of the IQ test. High IL-10 levels were significantly associated with low stress levels only in the right-brain-dominant group. High IL-10 and IFN-gamma levels have been associated with high scores of arithmetic intelligence. TNF-alpha and IL-6 were negatively associated with vocabulary scores and full-scale IQ, but IL-10 and IFN-gamma were positively associated with scores on the arithmetic subtest in left-brain-dominant subjects. On the other hand, IL-10 showed positive correlations with scores for vocabulary and for vocabulary and arithmetic in right-brain-dominant subjects. Furthermore, we found significant linear regression models which can show integrative associations and contribution on emotional and cognitive intelligence. Thus, we demonstrated that cytokines, stress, and emotional and cognitive intelligence are closely connected one another related to brain structure and functions. Also, the pro-inflammatory cytokines TNF-alpha and IL-6 had negative effects, whereas the anti-inflammatory cytokines (e.g., IL-10 and IFN-gamma) showed beneficial effects, on stress levels, and multiple dimensions of emotional and cognitive intelligence. Additionally, these relationships among cytokines, stress, and emotional and cognitive intelligence differed depending on right and left hemispheric dominance.

Sleeping, sleeping environments, and human errors in South Korean male train drivers.

OBJECTIVES: Reducing human errors caused by daytime sleepiness among train drivers is important to prevent train accidents. Our purpose of the study was to investigate the association among sleep, workplace sleeping environments, and human errors. METHODS: We recruited 144 South Korean train drivers belongs to the Korean Railroad Corporation. This cross-sectional data was analyzed to investigate the association of insomnia (insomnia severity index), sleep quality (Pittsburgh sleep quality index), obstructive sleep apnea (Berlin questionnaire), and daytime sleepiness (Epworth scale) with human error and near-miss experiences. We examined whether human error and near-miss events were associated with various sleeping environments at work and at home after adjusting for the sleep indices. RESULTS: The experience of human errors was associated with insomnia and daytime sleepiness, and near-miss events were associated with insomnia among South Korean drivers. Sleeping environments including cold temperature and odor were related to both human errors and near-miss events among South Korean train drivers, after adjusted for age, working years, shiftwork, obesity, smoking, binge drinking, regular exercise, caffeine consumption, sleep quality, severity of insomnia, obstructive sleep apnea, and daytime sleepiness. CONCLUSIONS: The train drivers' workplace sleeping environment is significantly associated with human error events and near-miss events after adjusting for sleep quality, insomnia, obstructive sleep apnea, and daytime sleepiness. To prevent train accidents caused by human errors, more attention is necessary for improving workplace sleeping environments.

Comparison of efficacy and complications between radiofrequency ablation and repeat surgery in the treatment of locally recurrent thyroid cancers: a single-center propensity score matching study.

PURPOSE: To compare the efficacy and complication rates of radiofrequency ablation (RFA) and repeat surgery in the treatment of locally recurrent thyroid cancers. MATERIALS AND METHODS: A total of 221 patients with locally recurrent thyroid cancers who underwent either RFA (n = 96) or repeat surgery (n = 125) between March 2008 and March 2017 were retrospectively enrolled (range of follow-up, 1-10 years). Each cohort consisted of 70 patients after propensity score adjustment. Patients with more than three recurrent lesions were excluded. The primary and secondary end points were recurrence-free survival and complication rates, respectively. Recurrence-free survival curves were compared via the log-rank test. The complications-voice changes, hypocalcemia, and immediate procedural complications-were compared between the groups. In addition, pretreatment serum thyroglobulin (Tg) levels and those at the last follow-up were also compared between the two groups to examine therapeutic efficacy. RESULTS: After propensity score matching, both groups showed no significant differences in baseline characteristics. The recurrence-free survival rates were comparable between the RFA and surgery groups (p = .2). There were no significant differences in mean serum Tg levels and their mean decrease after treatment between the groups (p = .891 and p = .963, respectively). Immediate procedural complications and voice changes also showed no significant between-group differences (p = .316, p = .084, respectively). Hypocalcemia occurred only in the repeat surgery group (n = 18). Overall complications were significantly more frequent in the repeat surgery group (RFA, n = 7; surgery, n = 27; p < .001). CONCLUSION: RFA may be an effective and safe alternative to repeat surgery in the treatment of a small number of locally recurrent thyroid cancers.

Disturbed retrieval network and prospective memory decline in postpartum women.

Prospective memory (PM) refers to the ability to remember to execute an intended action in the future. For successful PM performance, both top-down strategic monitoring and bottom-up spontaneous retrieval processes need to be appropriately recruited. We assessed PM performance and used fMRI to discover relevant neural correlates and possible predictors for PM performance in 25 postpartum and 26 nulliparous age- and education-matched women. Postpartum women showed decreased PM performance, a higher number of nocturnal awakenings, and lower estradiol level. The postpartum women had decreased functional connectivity (FC) in the right hippocampus and ventral frontoparietal networks (FPN) during retrieval-dominant PM trials relative to maintenance-dominant ongoing trials in the PM block. On multivariate analyses, decreased FC between the right hippocampus and ventral FPN and a higher number of nocturnal awakenings were independent predictors for poor PM performance after adjusting for age, education, estradiol level, and depressive symptoms. On mediation analyses, the estradiol level was found to have an indirect effect on PM accuracy via altered FC as a mediator. This suggests that decreased FC within the spontaneous retrieval-related regions including the right hippocampus and ventral FPN, disrupted sleep rhythms, and decreased estradiol level may contribute to poor PM performance in postpartum women.