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Purpose: Accurate and automated early survival prediction is critical for patients with glioblastoma (GBM) as their poor prognosis requires timely treatment decision-making. To address this need, we developed a deep learning (DL)-based end-to-end workflow for GBM overall survival (OS) prediction using pre-resection basic structural multiparametric magnetic resonance images (Bas-mpMRI) with a multi-institutional public dataset and evaluated it with an independent dataset of patients on a prospective institutional clinical trial., Materials and Methods: The proposed end-to-end workflow includes a skull-stripping model, a GBM sub-region segmentation model and an ensemble learning-based OS prediction model. The segmentation model utilizes skull-stripped Bas-mpMRIs to segment three GBM sub-regions. The segmented GBM is fed into the contrastive learning-based OS prediction model to classify the patients into different survival groups. Our datasets include both a multi-institutional public dataset from Medical Image Computing and Computer Assisted Intervention (MICCAI) Brain Tumor Segmentation (BraTS) challenge 2020 with 235 patients, and an institutional dataset from a 5-fraction SRS clinical trial with 19 GBM patients. Each data entry consists of pre-operative Bas-mpMRIs, survival days and patient ages. Basic clinical characteristics are also available for SRS clinical trial data. The multi-institutional public dataset was used for workflow establishing (90% of data) and initial validation (10% of data). The validated workflow was then evaluated on the institutional clinical trial data., Results: Our proposed OS prediction workflow achieved an area under the curve (AUC) of 0.86 on the public dataset and 0.72 on the institutional clinical trial dataset to classify patients into 2 OS classes as long-survivors (>12 months) and short-survivors (<12 months), despite the large variation in Bas-mpMRI protocols. In addition, as part of the intermediate results, the proposed workflow can also provide detailed GBM sub-regions auto-segmentation with a whole tumor Dice score of 0.91., Conclusion: Our study demonstrates the feasibility of employing this DL-based end-to-end workflow to predict the OS of patients with GBM using only the pre-resection Bas-mpMRIs. This DL-based workflow can be potentially applied to assist timely clinical decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We aimed to build a robust classifier for the MGMT methylation status of glioblastoma in multiparametric MRI. We focused on multi-habitat deep image descriptors as our basic focus. A subset of the BRATS 2021 MGMT methylation dataset containing both MGMT class labels and segmentation masks was used. A comprehensive mask fusion approach was developed to select relevant image crops of diseased tissue. These fusion masks, which were guided by multiple sequences, helped collect information from the regions that seem disease-free to radiologists in standard MRI sequences while harboring pathology. Integrating the information in different MRI sequences and leveraging the high entropic capacity of deep neural networks, we built a 3D ROI-based custom CNN classifier for the automatic prediction of MGMT methylation status of glioblastoma in multi-parametric MRI. Single sequence-based classifiers reached intermediate predictive performance with 0.65, 0.71, 0.77, and 0.82 accuracy for T1W, T2W, T1 contrast-enhanced, and FLAIR sequences, respectively. The multiparametric classifier using T1 contrast-enhanced and FLAIR images reached 0.88 accuracy. The accuracy of the four-input model that used all sequences was 0.81. The best model reached 0.90 ROC AUC value. Integrating human knowledge in the form of relevant target selection was a useful approach in MGMT methylation status prediction in MRI. Exploration of means to integrate radiology knowledge into the models and achieve human-machine collaboration may help to develop better models. MGMT methylation status of glioblastoma is an important prognostic marker and is also important for treatment decisions. The preoperative non-invasive predictive ability and the explanation tools of the developed model may help clinicians to better understand imaging phenotypes of MGMT methylation status of glial tumors., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free survival and correlates with treatment response. We also identify genetic variants and transcriptomic pathways associated with progression risk, highlighting links to tumor growth and immune response. This radiogenomic study in pLGGs provides a framework for the identification of high-risk patients who may benefit from targeted therapies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Radiomics and deep learning (DL) can individually and efficiently identify the pathological type of brain metastases (BMs)., Purpose: To investigate the feasibility of utilizing multi-parametric MRI-based deep transfer learning radiomics (DTLR) for the classification of lung adenocarcinoma (LUAD) and non-LUAD BMs., Material and Methods: A retrospective analysis was performed on 342 patients with 1389 BMs. These instances were randomly assigned to a training set of 273 (1179 BMs) and a testing set of 69 (210 BMs) in an 8:2 ratio. Eight machine learning algorithms were employed to construct the radiomics models. A DL model was developed using four pre-trained convolutional neural networks (CNNs). The DTLR model was formulated by integrating the optimal performing radiomics model and the DL model using a classification probability averaging approach. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were utilized to assess the performance and clinical utility of the models., Results: The AUC for the optimal radiomics and DL model in the testing set were 0.824 (95% confidence interval [CI]= 0.726-0.923) and 0.775 (95% CI=0.666-0.884), respectively. The DTLR model demonstrated superior discriminatory power, achieving an AUC of 0.880 (95% CI=0.803-0.957). In addition, the DTLR model exhibited good consistency between actual and predicted probabilities based on the calibration curve and DCA analysis, indicating its significant clinical value., Conclusion: Our study's DTLR model demonstrated high diagnostic accuracy in distinguishing LUAD from non-LUAD BMs. This method shows potential for the non-invasive identification of the histological subtype of BMs., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This comprehensive review explores the role of deep learning (DL) in glioma segmentation using multiparametric magnetic resonance imaging (MRI) data. The study surveys advanced techniques such as multiparametric MRI for capturing the complex nature of gliomas. It delves into the integration of DL with MRI, focusing on convolutional neural networks (CNNs) and their remarkable capabilities in tumor segmentation. Clinical applications of DL-based segmentation are highlighted, including treatment planning, monitoring treatment response, and distinguishing between tumor progression and pseudo-progression. Furthermore, the review examines the evolution of DL-based segmentation studies, from early CNN models to recent advancements such as attention mechanisms and transformer models. Challenges in data quality, gradient vanishing, and model interpretability are discussed. The review concludes with insights into future research directions, emphasizing the importance of addressing tumor heterogeneity, integrating genomic data, and ensuring responsible deployment of DL-driven healthcare technologies. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Purpose: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage by leveraging advanced MRI techniques to explore the relationships among tumor characteristics, glymphatic function, and aquaporin-4 (AQP4) expression levels., Experimental Design: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and multiparametric MRI for quantitative brain mapping. Tumor and peritumor tissues were analyzed for AQP4 expression levels via immunofluorescence. Correlations among MRI parameters, glymphatic function (DTI-ALPS index), and AQP4 expression levels were statistically assessed., Results: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), patients with brain tumor exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; P = 0.001) and increased cerebrospinal fluid volume (201.376 cm³ vs. 115.957 cm³; P = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, P < 0.001), whereas AQP4 expression levels correlated positively with peritumoral brain edema volume (r: 0.989, P < 0.001) and negatively with proton density in peritumoral brain edema areas (ρ: -0.506, P < 0.001)., Conclusions: Our findings highlight the interplay among tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, demonstrating the utility of DTI-ALPS and multiparametric MRI in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system. See related commentary by Surov and Borggrefe, p. 4813., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Distinguishing between tumor recurrence and pseudoprogression (PsP) in high-grade glioma postoperatively is challenging. This study aims to enhance this differentiation using a combination of intratumoral and peritumoral radiomics., Purpose: To assess the effectiveness of intratumoral and peritumoral radiomics in improving the differentiation between high-grade glioma recurrence and pseudoprogression after surgery., Material and Methods: A total of 109 cases were randomly divided into training and validation sets, with 1316 features extracted from intratumoral and peritumoral volumes of interest (VOIs) on conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) maps. Feature selection was performed using the mRMR algorithm, resulting in intratumoral (100 features), peritumoral (100 features), and combined (200 features) subsets. Optimal features were then selected using PCC and RFE algorithms and modeled using LR, SVM, and LDA classifiers. Diagnostic performance was compared using area under the receiver operating characteristic curve (AUC), evaluated in the validation set. A nomogram was established using radscores from intratumoral, peritumoral, and combined models., Results: The combined model, utilizing 14 optimal features (8 peritumoral, 6 intratumoral) and LR as the best classifier, outperformed the single intratumoral and peritumoral models. In the training set, the AUC values for the combined model, intratumoral model, and peritumoral model were 0.938, 0.921, and 0.847, respectively; in the validation set, the AUC values were 0.841, 0.755, and 0.705. The nomogram model demonstrated AUCs of 0.960 (training set) and 0.850 (validation set)., Conclusion: The combination of intratumoral and peritumoral radiomics is effective in distinguishing high-grade glioma recurrence from pseudoprogression after surgery., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To evaluate the performance of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics in distinguishing between glioblastoma (Gb) and solitary brain metastasis (SBM)., Materials and Methods: In this retrospective study, NODDI images were curated from 109 patients with Gb (n = 57) or SBM (n = 52). Automatically segmented multiple volumes of interest (VOIs) encompassed the main tumor regions, including necrosis, solid tumor, and peritumoral edema. Radiomics features were extracted for each main tumor region, using three NODDI parameter maps. Radiomics models were developed based on these three NODDI parameter maps and their amalgamation to differentiate between Gb and SBM. Additionally, radiomics models were constructed based on morphological magnetic resonance imaging (MRI) and diffusion imaging (diffusion-weighted imaging [DWI]; diffusion tensor imaging [DTI]) for performance comparison., Results: The validation dataset results revealed that the performance of a single NODDI parameter map model was inferior to that of the combined NODDI model. In the necrotic regions, the combined NODDI radiomics model exhibited less than ideal discriminative capabilities (area under the receiver operating characteristic curve [AUC] = 0.701). For peritumoral edema regions, the combined NODDI radiomics model achieved a moderate level of discrimination (AUC = 0.820). Within the solid tumor regions, the combined NODDI radiomics model demonstrated superior performance (AUC = 0.904), surpassing the models of other VOIs. The comparison results demonstrated that the NODDI model was better than the DWI and DTI models, while those of the morphological MRI and NODDI models were similar., Conclusion: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM., Clinical Relevance Statement: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM, and radiomics features can be incorporated into the multidimensional phenotypic features that describe tumor heterogeneity., Key Points: • The neurite orientation dispersion and density imaging (NODDI) radiomics model showed promising performance for preoperative discrimination between glioblastoma and solitary brain metastasis. • Compared with other tumor volumes of interest, the NODDI radiomics model based on solid tumor regions performed best in distinguishing the two types of tumors. • The performance of the single-parameter NODDI model was inferior to that of the combined-parameter NODDI model., (© 2024. The Author(s).)

Background: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT)., Methods: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats., Discussion: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma., Trial Registration: ClinicalTrials.gov ID: NCT02613988., (© 2024. The Author(s).)

Objective: The early differential diagnosis of the postoperative recurrence or pseudoprogression (psPD) of a glioma is of great guiding significance for individualized clinical treatment. This study aimed to evaluate the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics model to distinguish between the postoperative recurrence and psPD of a glioma early on and in a noninvasive manner., Methods: A total of 52 patients with gliomas who attended the Hainan Provincial People's Hospital between 2000 and 2021 and met the inclusion criteria were selected for this study. 1137 and 1137 radiomic features were extracted from T1 enhanced and T2WI/FLAIR sequence images, respectively.After clearing some invalid information and LASSO screening, a total of 9 and 10 characteristic radiological features were extracted and randomly divided into the training set and the test set according to 7:3 ratio. Select-Kbest and minimum Absolute contraction and selection operator (LASSO) were used for feature selection. Support vector machine and logistic regression were used to form a multi-parameter model for training and prediction. The optimal sequence and classifier were selected according to the area under the curve (AUC) and accuracy., Results: Radiomic models 1, 2 and 3 based on T1WI, T2FLAIR and T1WI + T2T2FLAIR sequences have better performance in the identification of postoperative recurrence and false progression of T1 glioma. The performance of model 2 is more stable, and the performance of support vector machine classifier is more stable. The multiparameter model based on CE-T1 + T2WI/FLAIR sequence showed the best performance (AUC:0.96, sensitivity: 0.87, specificity: 0.94, accuracy: 0.89,95% CI:0.93-1)., Conclusion: The use of multiparametric MRI-based radiomics provides a noninvasive, stable, and accurate method for differentiating between the postoperative recurrence and psPD of a glioma, which allows for timely individualized clinical treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Tumor segmentation is essential in surgical and treatment planning and response assessment and monitoring in pediatric brain tumors, the leading cause of cancer-related death among children. However, manual segmentation is time-consuming and has high interoperator variability, underscoring the need for more efficient methods. After training, we compared 2 deep-learning-based 3D segmentation models, DeepMedic and nnU-Net, with pediatric-specific multi-institutional brain tumor data based on multiparametric MR images., Materials and Methods: Multiparametric preoperative MR imaging scans of 339 pediatric patients ( n  = 293 internal and n  = 46 external cohorts) with a variety of tumor subtypes were preprocessed and manually segmented into 4 tumor subregions, ie, enhancing tumor, nonenhancing tumor, cystic components, and peritumoral edema. After training, performances of the 2 models on internal and external test sets were evaluated with reference to ground truth manual segmentations. Additionally, concordance was assessed by comparing the volume of the subregions as a percentage of the whole tumor between model predictions and ground truth segmentations using the Pearson or Spearman correlation coefficients and the Bland-Altman method., Results: The mean Dice score for nnU-Net internal test set was 0.9 (SD, 0.07) (median, 0.94) for whole tumor; 0.77 (SD, 0.29) for enhancing tumor; 0.66 (SD, 0.32) for nonenhancing tumor; 0.71 (SD, 0.33) for cystic components, and 0.71 (SD, 0.40) for peritumoral edema, respectively. For DeepMedic, the mean Dice scores were 0.82 (SD, 0.16) for whole tumor; 0.66 (SD, 0.32) for enhancing tumor; 0.48 (SD, 0.27) for nonenhancing tumor; 0.48 (SD, 0.36) for cystic components, and 0.19 (SD, 0.33) for peritumoral edema, respectively. Dice scores were significantly higher for nnU-Net ( P  ≤ .01). Correlation coefficients for tumor subregion percentage volumes were higher (0.98 versus 0.91 for enhancing tumor, 0.97 versus 0.75 for nonenhancing tumor, 0.98 versus 0.80 for cystic components, 0.95 versus 0.33 for peritumoral edema in the internal test set). Bland-Altman plots were better for nnU-Net compared with DeepMedic. External validation of the trained nnU-Net model on the multi-institutional Brain Tumor Segmentation Challenge in Pediatrics (BraTS-PEDs) 2023 data set revealed high generalization capability in the segmentation of whole tumor, tumor core (a combination of enhancing tumor, nonenhancing tumor, and cystic components), and enhancing tumor with mean Dice scores of 0.87 (SD, 0.13) (median, 0.91), 0.83 (SD, 0.18) (median, 0.89), and 0.48 (SD, 0.38) (median, 0.58), respectively., Conclusions: The pediatric-specific data-trained nnU-Net model is superior to DeepMedic for whole tumor and subregion segmentation of pediatric brain tumors., (© 2024 by American Journal of Neuroradiology.)

Prediction of glioma is crucial to provide a precise treatment plan to optimize the prognosis of children with glioma. However, studies on the grading of pediatric gliomas using radiomics are limited. Meanwhile, existing methods are mainly based on only radiomics features, ignoring intuitive information about tumor morphology on traditional imaging features. This study aims to utilize multiparametric magnetic resonance imaging (MRI) to identify high-grade and low-grade gliomas in children and establish a classification model based on radiomics features and clinical features. A total of 85 children with gliomas underwent tumor resection, and part of the tumor tissue was examined pathologically. Patients were categorized into high-grade and low-grade groups according to World Health Organization guidelines. Preoperative multiparametric MRI data, including contrast-enhanced T1-weighted imaging, T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted images, and apparent diffusion coefficient sequences, were obtained and labeled by two radiologists. The images were preprocessed, and radiomics features were extracted for each MRI sequence. Feature selection methods were used to select radiomics features, and statistically significant clinical features were identified using t-tests. The selected radiomics features and conventional MRI features were used to train the AutoGluon models. The improved model, based on radiomics features and conventional MRI features, achieved a balanced classification accuracy of 66.59%. The cross-validated areas under the receiver operating characteristic curve for the classifier of AutoGluon frame were 0.8071 on the test dataset. The results indicate that the performance of AutoGluon models can be improved by incorporating conventional MRI features, highlighting the importance of the experience of radiologists in accurately grading pediatric gliomas. This method can help predict the grade of pediatric glioma before pathological examination and assist in determining the appropriate treatment plan, including radiotherapy, chemotherapy, drugs, and gene surgery., (© 2024. The Author(s).)

Aim: We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic patterns with hemodynamic information., Materials and Methods: Preoperative data from 69 high-grade gliomas (HGG) patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after concurrent chemoradiotherapy (CCRT). Four vascular habitats were automatically segmented by multiparametric magnetic resonance imaging (MRI). The metabolic information, either at enhancing or edema tumor regions, was obtained by two neuroradiologists. The relative habitat volumes were used for weight estimation procedures for computing the coefficients of a linear regression model using weighted least squares (WLS) for metabolite semiquantifications (i.e. the Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses are used to obtain the odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients., Results: There was a strongly correlation between perfusion indexes and the Cho/Cr ratio (rCBV, r=0.71) or Cho/NAA ratio (rCBV, r=0.66) at high-angiogenic enhancing tumor habitats (HAT) habitat. Compared isocitrate dehydrogenase (IDH) mutation to their wild type, the IDH wild type had significantly decreased Cho/Cr ratio (IDH mutation: Cho/Cr ratio = 2.44 ± 0.33, IDH wildtype: Cho/Cr ratio = 2.66 ± 0.36, p=0.02) and Cho/NAA ratio (IDH mutation: Cho/Cr ratio = 4.59 ± 0.61, IDH wildtype: Cho/Cr ratio = 4.99 ± 0.66, p=0.022) at the HAT. The C-index for the median progression-free survival (PFS) prediction was 0.769 for the Cho/NAA nomogram and 0.747 for the Cho/Cr nomogram through 1000 bootstrapping validation., Conclusions: Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patients post-CCRT., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Rationale and Objectives: Tumor-infiltrating CD8 + T cells play a key role in glioblastoma (GB) development, malignant progression, and recurrence. The aim of the study was to establish nomograms based on the Visually AcceSAble Rembrandt Images (VASARI) features of multiparametric magnetic resonance imaging (MRI) to determine the expression levels of tumor-infiltrating CD8 + T cells in patients with GB., Materials and Methods: Pathological and imaging data of 140 patients with GB confirmed by surgery and pathology were retrospectively analyzed. The levels of tumor-infiltrating CD8 + T cells in tumor tissue samples obtained from patients were quantified using immunohistochemical staining. Patients were divided into high and low CD8 expression groups. The MRI images of patients with GB were analyzed by two radiologists using the VASARI scoring system., Results: A total of 25 MRI-based VASARI imaging features were evaluated by two neuroradiologists. The features with the greatest predictive power for CD8 expression levels were, cystic (OR, 3.063; 95% CI: 1.387, 6.766; P = 0.006), hemorrhage (OR, 2.980; 95% CI: 1.172, 7.575; P = 0.022), and ependymal extension (OR, 0.257; 95% CI: 0.114 0.581; P = 0.001). A logistic regression model based on these three features showed better sample predictive performance (AUC=0.745; 95% CI: 0.665, 0.825; Sensitivity=0.527; Specificity=0.857)., Conclusion: The VASARI feature-based nomogram model can show promise to predict the level of infiltrative CD8 expression in GB tumors non-invasively for earlier tissue diagnosis and more aggressive treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine if machine learning (ML) or deep learning (DL) pipelines perform better in AI-based three-class classification of glioblastoma (GBM), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL)., Methodology: Retrospective analysis included 502 cases for training (208 GBM, 67 PCNSL and 227 IMD), with external validation on 86 cases (27:27:32). Multiparametric MRI images (T1W, T2W, FLAIR, DWI and T1-CE) were co-registered, resampled, denoised and intensity normalized, followed by semiautomatic 3D segmentation of the enhancing tumor (ET) and peritumoral region (PTR). Model performance was assessed using several ML pipelines and 3D-convolutional neural networks (3D-CNN) using sequence specific masks, as well as combination of masks. All pipelines were trained and evaluated with 5-fold nested cross-validation on internal data followed by external validation using multi-class AUC., Results: Two ML models achieved similar performance on test set, one using T2-ET and T2-PTR masks (AUC: 0.885, 95% CI: [0.816, 0.935] and another using T1-CE-ET and FLAIR-PTR mask (AUC: 0.878, CI: [0.804, 0.930]). The best performing DL models achieved an AUC of 0.854, (CI [0.774, 0.914]) on external data using T1-CE-ET and T2-PTR masks, followed by model derived from T1-CE-ET, ADC-ET and FLAIR-PTR masks (AUC: 0.851, CI [0.772, 0.909])., Conclusion: Both ML and DL derived pipelines achieved similar performance. T1-CE mask was used in three of the top four overall models. Additionally, all four models had some mask derived from PTR, either T2WI or FLAIR., Competing Interests: Declaration of Competing Interest GB: Research grant from Foundation of Sarcoidosis Research, that is unrelated to the submitted work. SM: Grant funding from NIH/ NCI, NovoCure Inc and Galelio CDS, unrelated to current work. SR: Full time employee of Avid Radiopharmaceuticals. MS: Inventor on patents and patent applications in computer vision and medical image analysis; Co-founder of Medical Imaging Applications, LLC, Coralville, Iowa, USA and VIDA Diagnostics, Inc., Coralville, Iowa, USA. Rest of the authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: The Image Biomarker Standardization Initiative has helped improve the computational reproducibility of MRI radiomics features. Nonetheless, the MRI sequences and features with high imaging reproducibility are yet to be established. To determine reproducible multiparametric MRI radiomics features across test-retest, multi-scanner, and computational reproducibility comparisons, and to evaluate their clinical value in brain tumor diagnosis., Methods: To assess reproducibility, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) were acquired from three 3-T MRI scanners using standardized phantom, and radiomics features were extracted using two computational algorithms. Reproducible radiomics features were selected when the concordance correlation coefficient value above 0.9 across multiple sessions, scanners, and computational algorithms. Random forest classifiers were trained with reproducible features (n = 117) and validated in a clinical cohort (n = 50) to evaluate whether features with high reproducibility improved the differentiation of glioblastoma from primary central nervous system lymphomas (PCNSLs)., Results: Radiomics features from T2WI demonstrated higher repeatability (65-94%) than those from DWI (38-48%) or T1WI (2-92%). Across test-retest, multi-scanner, and computational comparisons, T2WI provided 41 reproducible features, DWI provided six, and T1WI provided two. The performance of the classification model with reproducible features was higher than that using non-reproducible features in both training set (AUC, 0.916 vs. 0.877) and validation set (AUC, 0.957 vs. 0.869)., Conclusion: Radiomics features with high reproducibility across multiple sessions, scanners, and computational algorithms were identified, and they showed higher diagnostic performance than non-reproducible radiomics features in the differentiation of glioblastoma from PCNSL., Clinical Relevance Statement: By identifying the radiomics features showing higher multi-machine reproducibility, our results also demonstrated higher radiomics diagnostic performance in the differentiation of glioblastoma from PCNSL, paving the way for further research designs and clinical application in neuro-oncology., Key Points: • Highly reproducible radiomics features across multiple sessions, scanners, and computational algorithms were identified using phantom and applied to clinical diagnosis. • Radiomics features from T2-weighted imaging were more reproducible than those from T1-weighted and diffusion-weighted imaging. • Radiomics features with good reproducibility had better diagnostic performance for brain tumors than features with poor reproducibility., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To establish and validate a radiomics nomogram for preoperative prediction of isocitrate dehydrogenase (IDH) mutation status of gliomas in a multicenter setting., Methods: 414 gliomas patients were collected (306 from local institution and 108 from TCGA). 851 radiomics features were extracted from contrast-enhanced T1-weighted (CE-T1W) and fluid attenuated inversion recovery (FLAIR) sequence, respectively. The features were refined using least absolute shrinkage and selection operator (LASSO) regression combing 10-fold cross-validation. The optimal radiomics features with age and sex were processed by multivariate logistic regression analysis to construct a prediction model, which was developed in the training dataset and assessed in the test and validation dataset. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were applied in the test and external validation datasets to evaluate the performance of the prediction model., Results: Ten robust radiomics features were selected from the 1702 features (four CE-T1W features and six FLAIR features). A nomogram was plotted to represent the prediction model. The accuracy and AUC of the radiomics nomogram achieved 86.96% and 0.891(0.809-0.947) in the test dataset and 84.26% and 0.881(0.805-0.936) in the external validation dataset (all p < 0.05). The positive predictive value (PPV) and negative predictive value (NPV) were 83.72% and 87.75% in the test dataset and 87.81% and 82.09% in the external validation dataset., Conclusion: IDH genotypes of gliomas can be identified by preoperative multiparametric MRI radiomics nomogram and might be clinically meaningful for treatment strategy and prognosis stratification of gliomas., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

High-grade gliomas are an aggressive and invasive malignancy which are susceptible to treatment resistance due to heterogeneity in intratumoral properties such as cell proliferation and density and perfusion. Non-invasive imaging approaches can measure these properties, which can then be used to calibrate patient-specific mathematical models of tumor growth and response. We employed multiparametric magnetic resonance imaging (MRI) to identify tumor extent (via contrast-enhanced T 1 -weighted, and T 2 -FLAIR) and capture intratumoral heterogeneity in cell density (via diffusion-weighted imaging) to calibrate a family of mathematical models of chemoradiation response in nine patients with unresected or partially resected disease. The calibrated model parameters were used to forecast spatially-mapped individual tumor response at future imaging visits. We then employed the Akaike information criteria to select the most parsimonious member from the family, a novel two-species model describing the enhancing and non-enhancing components of the tumor. Using this model, we achieved low error in predictions of the enhancing volume (median: - 2.5%, interquartile range: 10.0%) and a strong correlation in total cell count (Kendall correlation coefficient 0.79) at 3-months post-treatment. These preliminary results demonstrate the plausibility of using multiparametric MRI data to inform spatially-informative, biologically-based predictive models of tumor response in the setting of clinical high-grade gliomas.

Differentiating pseudoprogression from true tumor progression has become a significant challenge in follow-up of diffuse infiltrating gliomas, particularly high grade, which leads to a potential treatment delay for patients with early glioma recurrence. In this study, we proposed to use a multiparametric MRI data as a sequence input for the convolutional neural network with the recurrent neural network based deep learning structure to discriminate between pseudoprogression and true tumor progression. In this study, 43 biopsy-proven patient data identified as diffuse infiltrating glioma patients whose disease progressed/recurred were used. The dataset consists of five original MRI sequences; pre-contrast T1-weighted, post-contrast T1-weighted, T2-weighted, FLAIR, and ADC images as well as two engineered sequences; T1post-T1pre and T2-FLAIR. Next, we used three CNN-LSTM models with a different set of sequences as input sequences to pass through CNN-LSTM layers. We performed threefold cross-validation in the training dataset and generated the boxplot, accuracy, and ROC curve, AUC from each trained model with the test dataset to evaluate models. The mean accuracy for VGG16 models ranged from 0.44 to 0.60 and the mean AUC ranged from 0.47 to 0.59. For CNN-LSTM model, the mean accuracy ranged from 0.62 to 0.75 and the mean AUC ranged from 0.64 to 0.81. The performance of the proposed CNN-LSTM with multiparametric sequence data was found to outperform the popular convolutional CNN with a single MRI sequence. In conclusion, incorporating all available MRI sequences into a sequence input for a CNN-LSTM model improved diagnostic performance for discriminating between pseudoprogression and true tumor progression.

Purpose: To assess whether a machine-learning model based on texture features extracted from multiparametric magnetic resonance imaging could yield an accurate diagnosis in differentiating pilocytic astrocytoma from cystic oligodendrogliomas., Materials and Methods: The preoperative images from multisequences were used for tumor segmentation. Radiomic features were extracted and selected for machine-learning models. Semantic features and selected radiomic features from training data set were built, and the performance of each model was evaluated by receiver operating characteristic curve and accuracy from isolated testing data set., Results: In terms of different sequences, the best classifier was built by radiomic features extracted from enhanced T1WI-based classifier. The best model in our study turned out to be the gradient boosted trees classifier with an area under curve value of 0.99., Conclusion: Our study showed that gradient boosted trees based on texture features extracted from enhanced T1WI could become an additional tool for improving diagnostic accuracy to differentiate pilocytic astrocytoma from cystic oligodendroglioma.

Brain tumors are one of the most deadly diseases with a high mortality rate. The shape and size of the tumor are random during the growth process. Brain tumor segmentation is a brain tumor assisted diagnosis technology that separates different brain tumor structures such as edema and active and tumor necrosis tissues from normal brain tissue. Magnetic resonance imaging (MRI) technology has the advantages of no radiation impact on the human body, good imaging effect on structural tissues, and an ability to realize tomographic imaging of any orientation. Therefore, doctors often use MRI brain tumor images to analyze and process brain tumors. In these images, the tumor structure is only characterized by grayscale changes, and the developed images obtained by different equipment and different conditions may also be different. This makes it difficult for traditional image segmentation methods to deal well with the segmentation of brain tumor images. Considering that the traditional single-mode MRI brain tumor images contain incomplete brain tumor information, it is difficult to segment the single-mode brain tumor images to meet clinical needs. In this paper, a sparse subspace clustering (SSC) algorithm is introduced to process the diagnosis of multimodal MRI brain tumor images. In the absence of added noise, the proposed algorithm has better advantages than traditional methods. Compared with the top 15 in the Brats 2015 competition, the accuracy is not much different, being basically stable between 10 and 15. In order to verify the noise resistance of the proposed algorithm, this paper adds 5%, 10%, 15%, and 20% Gaussian noise to the test image. Experimental results show that the proposed algorithm has better noise immunity than a comparable algorithm., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Li Liu et al.)

Background: To evaluate whether functional and metabolic MRI can detect radiation-induced alterations in the adjacent areas after effective stereotactic radiosurgery (SRS) for brain metastases. If confirmed, these techniques may be suited for monitoring the timely stratification of patients for neuroprotective treatments after irradiation., Methods: Inclusion criteria were complete response, partial response, or stable disease on routine follow-up MR-scans. Multiparametric 3T-MRI was performed with diffusion-weighted imaging, dynamic susceptibility perfusion-weighted imaging, and two-dimensional proton MR-spectroscopy. Parameters were measured in the SRS-treated target and in the adjacent parenchyma up to both 0.75 cm and 1.5 cm from the target border., Results: Nineteen lesions in sixteen consecutive patients met the inclusion criteria. The median follow-up time was 39 months (range, 10-142) with 41 multiparametric MR-examinations in total. We found low values of N-acetyl-aspartate up to 1.5 cm from the target borders of SRS (P = 0.043) associated with high values of choline (P = 0.004) at the end of the observation period. Lactate levels in the adjacent tissue declined over time, whereas continuously high apparent-diffusion-coefficient values were noted (P < 0.001)., Conclusion: Multiparametric MRI can depict radiobiological effects and their time course at a distance from the effectively treated site after SRS for brain metastases, even if conventional MRI findings are inconspicuous.

Purpose: To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis., Patients and Methods: We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and near or distant RP. The predictive signatures for PFS and RP were evaluated on the basis of different classification schemes: single-institutional analysis, multi-institutional analysis with random partitioning of the data into discovery and replication cohorts, and multi-institutional assessment with data from institution 1 as the discovery cohort and data from institution 2 as the replication cohort., Results: These predictors achieved cross-validated classification performance (ie, area under the receiver operating characteristic curve) of 0.88 (single-institution analysis) and 0.82 to 0.83 (multi-institution analysis) for prediction of PFS and 0.88 (single-institution analysis) and 0.56 to 0.71 (multi-institution analysis) for prediction of RP., Conclusion: Imaging signatures of presurgical MP-MRI scans reveal relatively high predictability of time and location of GBM recurrence, subject to the patients receiving standard first-line chemoradiation therapy. Through its graphical user interface, CaPTk offers easy accessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.

Glioblastoma (GBM) is a heterogeneous and lethal brain cancer. These tumors are followed using magnetic resonance imaging (MRI), which is unable to precisely identify tumor cell invasion, impairing effective surgery and radiation planning. We present a novel hybrid model, based on multiparametric intensities, which combines machine learning (ML) with a mechanistic model of tumor growth to provide spatially resolved tumor cell density predictions. The ML component is an imaging data-driven graph-based semi-supervised learning model and we use the Proliferation-Invasion (PI) mechanistic tumor growth model. We thus refer to the hybrid model as the ML-PI model. The hybrid model was trained using 82 image-localized biopsies from 18 primary GBM patients with pre-operative MRI using a leave-one-patient-out cross validation framework. A Relief algorithm was developed to quantify relative contributions from the data sources. The ML-PI model statistically significantly outperformed (p < 0.001) both individual models, ML and PI, achieving a mean absolute predicted error (MAPE) of 0.106 ± 0.125 versus 0.199 ± 0.186 (ML) and 0.227 ± 0.215 (PI), respectively. Associated Pearson correlation coefficients for ML-PI, ML, and PI were 0.838, 0.518, and 0.437, respectively. The Relief algorithm showed the PI model had the greatest contribution to the result, emphasizing the importance of the hybrid model in achieving the high accuracy.

Quantitative mapping of hyperperfused and hypercellular regions of glioblastoma has been proposed to improve definition of tumor regions at risk for local recurrence following conventional radiation therapy. As the processing of the multiparametric dynamic contrast-enhanced (DCE-) and diffusion-weighted (DW-) magnetic resonance imaging (MRI) data for delineation of these subvolumes requires additional steps that go beyond the standard practices of target definition, we sought to devise a workflow to support the timely planning and treatment of patients. A phase II study implementing a multiparametric imaging biomarker for tumor hyperperfusion and hypercellularity consisting of DCE-MRI and high b-value DW-MRI to guide intensified (75 Gy/30 fractions) radiation therapy (RT) in patients with newly diagnosed glioblastoma was launched. In this report, the workflow and the initial imaging outcomes of the first 12 patients are described. Among all the first 12 patients, treatment was initiated within 6 weeks of surgery and within 2 weeks of simulation. On average, the combined hypercellular volume and high cerebral blood volume/tumor perfusion volume were 1.8 times smaller than the T1 gadolinium abnormality and 10 times smaller than the FLAIR abnormality. Hypercellular volume and high cerebral blood volume/tumor perfusion volume each identified largely distinct regions and showed 57% overlap with the enhancing abnormality, and minimal-to-no extension outside of the FLAIR. These results show the feasibility of implementing a workflow for multiparametric magnetic resonance-guided radiation therapy into clinical trials with a coordinated multidisciplinary team, and the unique and complementary tumor subregions identified by the combination of high b-value DW-MRI and DCE-MRI.

Purpose: To systematically review evidence regarding the association of multiparametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas., Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th, 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria., Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and highrisk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, α=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature., Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)