Search

Medical doctors rely on images of the human anatomy, such as magnetic resonance imaging (MRI), to localize regions of interest in the patient during diagnosis and treatment. Despite advances in medical imaging technology, the information conveyance remains unimodal. This visual representation fails to capture the complexity of the real, multisensory interaction with human tissue. However, perceiving multimodal information about the patient's anatomy and disease in real-time is critical for the success of medical procedures and patient outcome. We introduce a Multimodal Medical Image Interaction (MMII) framework to allow medical experts a dynamic, audiovisual interaction with human tissue in three-dimensional space. In a virtual reality environment, the user receives physically informed audiovisual feedback to improve the spatial perception of anatomical structures. MMII uses a model-based sonification approach to generate sounds derived from the geometry and physical properties of tissue, thereby eliminating the need for hand-crafted sound design. Two user studies involving 34 general and nine clinical experts were conducted to evaluate the proposed interaction framework's learnability, usability, and accuracy. Our results showed excellent learnability of audiovisual correspondence as the rate of correct associations significantly improved (p < 0.001) over the course of the study. MMII resulted in superior brain tumor localization accuracy (p < 0.05) compared to conventional medical image interaction. Our findings substantiate the potential of this novel framework to enhance interaction with medical images, for example, during surgical procedures where immediate and precise feedback is needed.

Background: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk., Methods: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of BMs (AURORA) retrospective study (training cohort: 253 patients from 2 centers; external test cohort: 99 patients from 5 centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (T2-FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set., Results: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (P < .001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively., Conclusions: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objectives: To generate sagittal T1-weighted fast spin echo (T1w FSE) and short tau inversion recovery (STIR) images from sagittal T2-weighted (T2w) FSE and axial T1w gradient echo Dixon technique (T1w-Dixon) sequences., Materials and Methods: This retrospective study used three existing datasets: "Study of Health in Pomerania" (SHIP, 3142 subjects, 1.5 Tesla), "German National Cohort" (NAKO, 2000 subjects, 3 Tesla), and an internal dataset (157 patients 1.5/3 Tesla). We generated synthetic sagittal T1w FSE and STIR images from sagittal T2w FSE and low-resolution axial T1w-Dixon sequences based on two successively applied 3D Pix2Pix deep learning models. "Peak signal-to-noise ratio" (PSNR) and "structural similarity index metric" (SSIM) were used to evaluate the generated image quality on an ablations test. A Turing test, where seven radiologists rated 240 images as either natively acquired or generated, was evaluated using misclassification rate and Fleiss kappa interrater agreement., Results: Including axial T1w-Dixon or T1w FSE images resulted in higher image quality in generated T1w FSE (PSNR = 26.942, SSIM = 0.965) and STIR (PSNR = 28.86, SSIM = 0.948) images compared to using only single T2w images as input (PSNR = 23.076/24.677 SSIM = 0.952/0.928). Radiologists had difficulty identifying generated images (misclassification rate: 0.39 ± 0.09 for T1w FSE, 0.42 ± 0.18 for STIR) and showed low interrater agreement on suspicious images (Fleiss kappa: 0.09 for T1w/STIR)., Conclusions: Axial T1w-Dixon and sagittal T2w FSE images contain sufficient information to generate sagittal T1w FSE and STIR images., Clinical Relevance Statement: T1w fast spin echo and short tau inversion recovery can be retroactively added to existing datasets, saving MRI time and enabling retrospective analysis, such as evaluating bone marrow pathologies., Key Points: Sagittal T2-weighted images alone were insufficient for differentiating fat and water and to generate T1-weighted images. Axial T1w Dixon technique, together with a T2-weighted sequence, produced realistic sagittal T1-weighted images. Our approach can be used to retrospectively generate STIR and T1-weighted fast spin echo sequences., (© 2024. The Author(s).)

The rapid development of artificial intelligence (AI) has gained importance, with many tools already entering our daily lives. The medical field of radiation oncology is also subject to this development, with AI entering all steps of the patient journey. In this review article, we summarize contemporary AI techniques and explore the clinical applications of AI-based automated segmentation models in radiotherapy planning, focusing on delineation of organs at risk (OARs), the gross tumor volume (GTV), and the clinical target volume (CTV). Emphasizing the need for precise and individualized plans, we review various commercial and freeware segmentation tools and also state-of-the-art approaches. Through our own findings and based on the literature, we demonstrate improved efficiency and consistency as well as time savings in different clinical scenarios. Despite challenges in clinical implementation such as domain shifts, the potential benefits for personalized treatment planning are substantial. The integration of mathematical tumor growth models and AI-based tumor detection further enhances the possibilities for refining target volumes. As advancements continue, the prospect of one-stop-shop segmentation and radiotherapy planning represents an exciting frontier in radiotherapy, potentially enabling fast treatment with enhanced precision and individualization., (© 2024. The Author(s).)

Brain metastases (BMs) and high-grade gliomas (HGGs) are the most common and aggressive types of malignant brain tumors in adults, with often poor prognosis and short survival. As their clinical symptoms and image appearances on conventional magnetic resonance imaging (MRI) can be astonishingly similar, their accurate differentiation based solely on clinical and radiological information can be very challenging, particularly for "cancer of unknown primary", where no systemic malignancy is known or found. Non-invasive multiparametric MRI and radiomics offer the potential to identify these distinct biological properties, aiding in the characterization and differentiation of HGGs and BMs. However, there is a scarcity of publicly available multi-origin brain tumor imaging data for tumor characterization. In this paper, we introduce a multi-center, multi-origin brain tumor MRI (MOTUM) imaging dataset obtained from 67 patients: 29 with high-grade gliomas, 20 with lung metastases, 10 with breast metastases, 2 with gastric metastasis, 4 with ovarian metastasis, and 2 with melanoma metastasis. This dataset includes anonymized DICOM files alongside processed FLAIR, T1-weighted, contrast-enhanced T1-weighted, T2-weighted sequences images, segmentation masks of two tumor regions, and clinical data. Our data-sharing initiative is to support the benchmarking of automated tumor segmentation, multi-modal machine learning, and disease differentiation of multi-origin brain tumors in a multi-center setting., (© 2024. The Author(s).)

Background: Molecular glioblastoma (molGB) does not exhibit the histologic hallmarks of a grade 4 glioma but is nevertheless diagnosed as glioblastoma when harboring specific molecular markers. MolGB can easily be mistaken for similar-appearing lower-grade astrocytomas. Here, we investigated how advanced imaging could reflect the underlying tumor biology., Methods: Clinical and imaging data were collected for 7 molGB grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. Four neuroradiologists performed VASARI-scoring of conventional imaging, and their inter-reader agreement was assessed using Fleiss κ coefficient. To evaluate the potential of advanced imaging, 2-sample t test, 1-way ANOVA, Mann-Whitney U, and Kruskal-Wallis test were performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) that were extracted fully automatically from the whole tumor volume., Results: While conventional VASARI imaging features did not allow for reliable differentiation between glioma entities, rCBV was significantly higher in molGB compared to astrocytomas for the 5th and 95th percentile, mean, and median values ( P  < .05). ADC values were significantly lower in molGB than in astrocytomas for mean, median, and the 95th percentile ( P  < .05). Although no molGB showed contrast enhancement initially, we observed enhancement in the short-term follow-up of 1 patient., Discussion: Quantitative analysis of diffusion and perfusion parameters shows potential in reflecting the malignant tumor biology of molGB. It may increase awareness of molGB in a nonenhancing, "benign" appearing tumor. Our results support the emerging hypothesis that molGB might present glioblastoma captured at an early stage of gliomagenesis., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Purpose: According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively., Methods: Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [ 18 F]GE-180, dynamic amino acid PET using [ 18 F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [ 18 F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied., Results: TBR GE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [ 18 F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBR GE-180 features, parameters from kinetic and early static [ 18 F]FET PET images, age, and the features from TBR T2 images such as the kurtosis (0.97)., Conclusion: The findings suggest that incorporating TBR GE-180 features along with kinetic information from dynamic [ 18 F]FET PET, kurtosis from TBR T2 , and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management., (© 2024. The Author(s).)

Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos + cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin. DELiVR features a comprehensive toolkit for data visualization and can be customized to other cell types of interest, as we did here for microglia somata, using Fiji for dataset-specific training. We applied DELiVR to investigate cancer-related brain activity, unveiling an activation pattern that distinguishes weight-stable cancer from cancers associated with weight loss. Overall, DELiVR is a robust deep-learning tool that does not require advanced coding skills to analyze whole-brain imaging data in health and disease., (© 2024. The Author(s).)

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well-annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied clinical environments and providing personalized volumetric reports to patients undergoing BM treatment., Competing Interests: Conflicts of Interest No conflicts of interest to disclose.

Purpose: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity., Methods: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated., Results: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance., Conclusion: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future., (© 2024. The Author(s).)

Objectives: Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation., Materials and Methods: The consensus was achieved by a multi-stage process. Stage 1 comprised a definition screening, a retrospective analysis with semantic mapping of terms found in 22 workflow definitions, and the compilation of an initial baseline definition. Stages 2 and 3 consisted of a Delphi process with over 45 experts hailing from sites participating in the German Research Foundation (DFG) Priority Program 2177. Stage 2 aimed to achieve a broad consensus for a definition proposal, while stage 3 identified the importance of translational challenges., Results: Workflow definitions from 22 publications (published 2012-2020) were analyzed. Sixty-nine definition terms were extracted, mapped, and semantic ambiguities (e.g., homonymous and synonymous terms) were identified and resolved. The consensus definition was developed via a Delphi process. The final definition comprising seven phases and 37 aspects reached a high overall consensus (> 89% of experts "agree" or "strongly agree"). Two aspects reached no strong consensus. In addition, the Delphi process identified and characterized from the participating experts' perspective the ten most important challenges in radiomics workflows., Conclusion: To overcome semantic inconsistencies between existing definitions and offer a well-defined, broad, referenceable terminology, a consensus workflow definition for radiomics-based setups and a terms mapping to existing literature was compiled. Moreover, the most relevant challenges towards clinical application were characterized., Critical Relevance Statement: Lack of standardization represents one major obstacle to successful clinical translation of radiomics. Here, we report a consensus workflow definition on different aspects of radiomics studies and highlight important challenges to advance the clinical adoption of radiomics., Key Points: Published radiomics workflow terminologies are inconsistent, hindering standardization and translation. A consensus radiomics workflow definition proposal with high agreement was developed. Publicly available result resources for further exploitation by the scientific community., (© 2024. The Author(s).)

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes., (© 2024. The Author(s).)

Background: Meningiomas are the most common primary brain tumors. While most are benign (WHO grade 1) and have a favorable prognosis, up to one-fourth are classified as higher-grade, falling into WHO grade 2 or 3 categories. Recently, an integrated risk score (IRS) pertaining to tumor biology was developed and its prognostic relevance was validated in a large, multicenter study. We hypothesized imaging data to be reflective of the IRS. Thus, we assessed the potential of a machine learning classifier for its noninvasive prediction using preoperative magnetic resonance imaging (MRI)., Methods: In total, 160 WHO grade 2 and 3 meningioma patients from 2 university centers were included in this study. All patients underwent surgery with histopathological workup including methylation analysis. Preoperative MRI scans were automatically segmented, and radiomic parameters were extracted. Using a random forest classifier, 3 machine learning classifiers (1 multiclass classifier for IRS and 2 binary classifiers for low-risk and high-risk prediction, respectively) were developed in a training set (120 patients) and independently tested in a hold-out test set (40 patients)., Results: Multiclass IRS classification had a test set area under the curve (AUC) of 0.7, mostly driven by the difficulties in clearly separating medium-risk from high-risk patients. Consequently, a classifier predicting low-risk IRS versus medium-/high-risk showed a very high test accuracy of 90% (AUC 0.88). In particular, "sphericity" was associated with low-risk IRS classification., Conclusion: The IRS, in particular molecular low-risk, can be predicted from imaging data with high accuracy, making this important prognostic classification accessible by imaging., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Background: Awake craniotomy is the standard of care for treating language eloquent gliomas. However, depending on preoperative functionality, it is not feasible in each patient and selection criteria are highly heterogeneous. Thus, this study aimed to identify broadly applicable predictor variables allowing for a more systematic and objective patient selection., Methods: We performed post-hoc analyses of preoperative language status, patient and tumor characteristics including language eloquence of 96 glioma patients treated in a single neurosurgical center between 05/2018 and 01/2021. Multinomial logistic regression and stepwise variable selection were applied to identify significant predictors of awake surgery feasibility., Results: Stepwise backward selection confirmed that a higher number of paraphasias, lower age, and high language eloquence level were suitable indicators for an awake surgery in our cohort. Subsequent descriptive and ROC-analyses indicated a cut-off at ≤54 years and a language eloquence level of at least 6 for awake surgeries, which require further validation. A high language eloquence, lower age, preexisting semantic and phonological aphasic symptoms have shown to be suitable predictors., Conclusion: The combination of these factors may act as a basis for a systematic and standardized grading of patients' suitability for an awake craniotomy which is easily integrable into the preoperative workflow across neurosurgical centers., Competing Interests: BM received honoraria, consulting fees, and research grants from Medtronic (Meerbusch, Germany), Icotec AG (Altstätten, Switzerland), Nexstim Plc (Helsinki, Finland), and Relievant Medsystems Inc., (Sunnyvale, CA, USA), honoraria, and research grants from Ulrich Medical (Ulm, Germany), honoraria and consulting fees from Spineart Deutschland GmbH (Frankfurt, Germany) and DePuy Synthes (West Chester, PA, USA), and royalties from Spineart Deutschland GmbH (Frankfurt, Germany). SK is consultant for Ulrich Medical (Ulm, Germany), and Need Inc. (Santa Monica, CA, USA), and received honoraria from Nexstim Plc (Helsinki, Finland), Spineart Deutschland GmbH (Frankfurt, Germany), Medtronic (Meerbusch, Germany), and Carl Zeiss Meditec (Oberkochen, Germany). SK and BM received research grants and are consultants for Brainlab AG (Munich, Germany). SI is consultant for Brainlab AG (Munich, Germany) and received honoraria and consulting fees from Icotec AG (Altstätten, Switzerland), Carl Zeiss Meditec (Oberkochen, Germany), and Nexstim Plc (Helsinki, Finland). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kram, Neu, Schroeder, Wiestler, Meyer, Krieg and Ille.)

Background: Former comparisons between direct cortical stimulation (DCS) and navigated transcranial magnetic stimulation (nTMS) only focused on cortical mapping. While both can be combined with diffusion tensor imaging, their differences in the visualization of subcortical and even network levels remain unclear. Network centrality is an essential parameter in network analysis to measure the importance of nodes identified by mapping. Those include Degree centrality, Eigenvector centrality, Closeness centrality, Betweenness centrality, and PageRank centrality. While DCS and nTMS have repeatedly been compared on the cortical level, the underlying network identified by both has not been investigated yet., Method: 27 patients with brain lesions necessitating preoperative nTMS and intraoperative DCS language mapping during awake craniotomy were enrolled. Function-based connectome analysis was performed based on the cortical nodes obtained through the two mapping methods, and language-related network centralities were compared., Results: Compared with DCS language mapping, the positive predictive value of cortical nTMS language mapping is 74.1%, with good consistency of tractography for the arcuate fascicle and superior longitudinal fascicle. Moreover, network centralities did not differ between the two mapping methods. However, ventral stream tracts can be better traced based on nTMS mappings, demonstrating its strengths in acquiring language-related networks. In addition, it showed lower centralities than other brain areas, with decentralization as an indicator of language function loss., Conclusion: This study deepens the understanding of language-related functional anatomy and proves that non-invasive mapping-based network analysis is comparable to the language network identified via invasive cortical mapping., Competing Interests: Declaration of competing interest BM received honoraria, consulting fees, and research grants from Medtronic (Meerbusch, Germany), Icotec AG (Altstätten, Switzerland), and Relievant Medsystems Inc. (Sunnyvale, CA, USA), honoraria, and research grants from Ulrich Medical (Ulm, Germany), honoraria and consulting fees from Spineart Deutschland GmbH (Frankfurt, Germany) and DePuy Synthes (West Chester, PA, USA), and royalties from Spineart Deutschland GmbH (Frankfurt, Germany). SK is a consultant for Ulrich Medical (Ulm, Germany), and Need Inc. (Santa Monica, CA, USA), and received honoraria from Nexstim Plc (Helsinki, Finland), Spineart Deutschland GmbH (Frankfurt, Germany), Medtronic (Meerbusch, Germany) and Carl Zeiss Meditec (Oberkochen, Germany). SK, SI, and BM are consultants for Brainlab AG (Munich, Germany). However, all authors declare that they have no conflict of interest regarding the materials used or the results presented in this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To summarize evidence on the comparative value of amino acid (AA) PET and conventional MRI for prediction of overall survival (OS) in patients with recurrent high grade glioma (rHGG) under bevacizumab therapy., Methods: Medical databases were screened for studies with individual data on OS, follow-up MRI, and PET findings in the same patient. MRI images were assessed according to the RANO criteria. A receiver operating characteristic curve analysis was used to predict OS at 9 months., Results: Five studies with a total of 72 patients were included. Median OS was significantly lower in the PET-positive than in the PET-negative group. PET findings predicted OS with a pooled sensitivity and specificity of 76% and 71%, respectively. Corresponding values for MRI were 32% and 82%. Area under the curve and sensitivity were significantly higher for PET than for MRI., Conclusion: For monitoring of patients with rHGG under bevacizumab therapy, AA-PET should be preferred over RANO MRI., (© 2024. The Author(s).)

Objectives: T2 STIR MRI sequences can detect preclinical changes associated with periodontal inflammation, i.e. intraosseous edema in the tooth-supporting bone. In this study, we assessed whether MRI can be used for monitoring periodontal disease., Material and Methods: In a prospective cohort study, we examined 35 patients with periodontitis between 10/2018 and 04/2019 by using 3D isotropic T2-weighted short tau inversion recovery (STIR) and Fast Field Echo T1-weighted Black bone sequences. All patients received standardized clinical exams before and three months after non-surgical periodontal therapy. Bone marrow edema extent was quantified in the STIR sequence at 922 sites before and after treatment. Results were compared with standard clinical findings. Non-parametric statistical analysis was performed., Results: Non-surgical periodontal treatment caused significant improvement in mean probing depth (p < 0.001) and frequency of bleeding on probing (p < 0.001). The mean depth of osseous edema per site was reduced from a median [IQR] of 2 [1, 3] mm at baseline to 1 [0, 3] mm, (p < 0.001). Periodontal treatment reduced the frequency of sites with edema from 35 to 24% (p < 0.01)., Conclusion: The decrease of periodontal bone marrow edema, as observed with T2 STIR MR imaging, is indicative of successful periodontal healing., Clinical Relevance Statement: T2 STIR hyperintense bone marrow edema in the periodontal bone decreases after treatment and can therefore be used to evaluate treatment success. Furthermore, MRI reveals new options to depict hidden aspects of periodontitis., Key Points: • T2 STIR hyperintense periodontal intraosseous edema was prospectively investigated in 35 patients with periodontitis before and after treatment and compared to clinical outcomes. • The frequency of affected sites was reduced from 35 to 24% (p < 0.001), and mean edema depth was reduced from a median [IQR] of 2 [1, 3] mm at baseline to 1 [0, 3] mm 3 months after treatment. (p < 0.001). • T2 STIR sequences can be used to monitor the posttreatment course of periodontitis., (© 2023. The Author(s).)

So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM's relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann-Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic., Competing Interests: The authors declare no conflicts of interest.

Medulloblastoma and pilocytic astrocytoma are the two most common pediatric brain tumors with overlapping imaging features. In this proof-of-concept study, we investigated using a deep learning classifier trained on a multicenter data set to differentiate these tumor types. We developed a patch-based 3D-DenseNet classifier, utilizing automated tumor segmentation. Given the heterogeneity of imaging data (and available sequences), we used all individually available preoperative imaging sequences to make the model robust to varying input. We compared the classifier to diagnostic assessments by five readers with varying experience in pediatric brain tumors. Overall, we included 195 preoperative MRIs from children with medulloblastoma ( n = 69) or pilocytic astrocytoma ( n = 126) across six university hospitals. In the 64-patient test set, the DenseNet classifier achieved a high AUC of 0.986, correctly predicting 62/64 (97%) diagnoses. It misclassified one case of each tumor type. Human reader accuracy ranged from 100% (expert neuroradiologist) to 80% (resident). The classifier performed significantly better than relatively inexperienced readers ( p < 0.05) and was on par with pediatric neuro-oncology experts. Our proof-of-concept study demonstrates a deep learning model based on automated tumor segmentation that can reliably preoperatively differentiate between medulloblastoma and pilocytic astrocytoma, even in heterogeneous data.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated., Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM., Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates., Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT)., Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT., Competing Interests: BM works as consultants for Brainlab Brainlab AG, Feldkirchen. In addition, BM works as a consultant for Medtronic, Spineart, Icotec, Relievant and Depuy/Synthes, as a member of their advisory boards. Furthermore, BM reports financial relationships with Medtronic, Ulrich Medical, Brainlab, Spineart, Icotec, Relievant and Depuy/Synthes. He received personal fees and research grants for clinical studies from Medtronic, Ulrich Medical, Brainlab, Icotec and Relievant. All of this happened independently of the submitted work. BM receives royalties from and holds a patent with Spineart. All of the named potential conflicts of interest are unrelated to this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baumgart, Anetsberger, Aftahy, Wiestler, Bernhardt, Combs, Meyer, Schneider, Meyer and Gempt.)

Background: Conventional brain magnetic resonance imaging (MRI) produces image intensities that have an arbitrary scale, hampering quantification. Intensity scaling aims to overcome this shortfall. As neurodegenerative and inflammatory disorders may affect all brain compartments, reference regions within the brain may be misleading. Here we summarize approaches for intensity scaling of conventional T1-weighted (w) and T2w brain MRI avoiding reference regions within the brain., Methods: Literature was searched in the databases of Scopus, PubMed, and Web of Science. We included only studies that avoided reference regions within the brain for intensity scaling and provided validating evidence, which we divided into four categories: 1) comparative variance reduction, 2) comparative correlation with clinical parameters, 3) relation to quantitative imaging, or 4) relation to histology., Results: Of the 3825 studies screened, 24 fulfilled the inclusion criteria. Three studies used scaled T1w images, 2 scaled T2w images, and 21 T1w/T2w-ratio calculation (with double counts). A robust reduction in variance was reported. Twenty studies investigated the relation of scaled intensities to different types of quantitative imaging. Statistically significant correlations with clinical or demographic data were reported in 8 studies. Four studies reporting the relation to histology gave no clear picture of the main signal driver of conventional T1w and T2w MRI sequences., Conclusions: T1w/T2w-ratio calculation was applied most often. Variance reduction and correlations with other measures suggest a biologically meaningful signal harmonization. However, there are open methodological questions and uncertainty on its biological underpinning. Validation evidence on other scaling methods is even sparser., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wiltgen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Differentiating between benign and malignant vertebral fractures poses diagnostic challenges. Purpose To investigate the reliability of CT-based deep learning models to differentiate between benign and malignant vertebral fractures. Materials and Methods CT scans acquired in patients with benign or malignant vertebral fractures from June 2005 to December 2022 at two university hospitals were retrospectively identified based on a composite reference standard that included histopathologic and radiologic information. An internal test set was randomly selected, and an external test set was obtained from an additional hospital. Models used a three-dimensional U-Net encoder-classifier architecture and applied data augmentation during training. Performance was evaluated using the area under the receiver operating characteristic curve (AUC) and compared with that of two residents and one fellowship-trained radiologist using the DeLong test. Results The training set included 381 patients (mean age, 69.9 years ± 11.4 [SD]; 193 male) with 1307 vertebrae (378 benign fractures, 447 malignant fractures, 482 malignant lesions). Internal and external test sets included 86 (mean age, 66.9 years ± 12; 45 male) and 65 (mean age, 68.8 years ± 12.5; 39 female) patients, respectively. The better-performing model of two training approaches achieved AUCs of 0.85 (95% CI: 0.77, 0.92) in the internal and 0.75 (95% CI: 0.64, 0.85) in the external test sets. Including an uncertainty category further improved performance to AUCs of 0.91 (95% CI: 0.83, 0.97) in the internal test set and 0.76 (95% CI: 0.64, 0.88) in the external test set. The AUC values of residents were lower than that of the best-performing model in the internal test set (AUC, 0.69 [95% CI: 0.59, 0.78] and 0.71 [95% CI: 0.61, 0.80]) and external test set (AUC, 0.70 [95% CI: 0.58, 0.80] and 0.71 [95% CI: 0.60, 0.82]), with significant differences only for the internal test set ( P < .001). The AUCs of the fellowship-trained radiologist were similar to those of the best-performing model (internal test set, 0.86 [95% CI: 0.78, 0.93; P = .39]; external test set, 0.71 [95% CI: 0.60, 0.82; P = .46]). Conclusion Developed models showed a high discriminatory power to differentiate between benign and malignant vertebral fractures, surpassing or matching the performance of radiology residents and matching that of a fellowship-trained radiologist. © RSNA, 2024 See also the editorial by Booz and D'Angelo in this issue.

Background: With the ever-increasing amount of medical imaging data, the demand for algorithms to assist clinicians has amplified. Unsupervised anomaly detection (UAD) models promise to aid in the crucial first step of disease detection. While previous studies have thoroughly explored fairness in supervised models in healthcare, for UAD, this has so far been unexplored., Methods: In this study, we evaluated how dataset composition regarding subgroups manifests in disparate performance of UAD models along multiple protected variables on three large-scale publicly available chest X-ray datasets. Our experiments were validated using two state-of-the-art UAD models for medical images. Finally, we introduced subgroup-AUROC (sAUROC), which aids in quantifying fairness in machine learning., Findings: Our experiments revealed empirical "fairness laws" (similar to "scaling laws" for Transformers) for training-dataset composition: Linear relationships between anomaly detection performance within a subpopulation and its representation in the training data. Our study further revealed performance disparities, even in the case of balanced training data, and compound effects that exacerbate the drop in performance for subjects associated with multiple adversely affected groups., Interpretation: Our study quantified the disparate performance of UAD models against certain demographic subgroups. Importantly, we showed that this unfairness cannot be mitigated by balanced representation alone. Instead, the representation of some subgroups seems harder to learn by UAD models than that of others. The empirical "fairness laws" discovered in our study make disparate performance in UAD models easier to estimate and aid in determining the most desirable dataset composition., Funding: European Research Council Deep4MI., Competing Interests: Declaration of interests B.W. has received speaker honoraria from Novartis, Bayer and Philips. He holds a patent related to Apogenix APG101 for glioblastoma treatment and is a stockholder of the company “Need”., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Graded Prognostic Assessment (GPA) has been proposed for various brain metastases (BMs) tailored to the primary histology and molecular profiles. However, it does not consider whether patients have been operated on or not and does not include surgical outcomes as prognostic factors. The residual tumor burden (RTB) is a strong predictor of overall survival. We validated the GPA score and introduced "volumetric GPA" in the largest cohort of operated patients and further explored the role of RTB as an additional prognostic factor., Methods: A total of 630 patients with BMs between 2007 and 2020 were included. The four GPA components were analyzed. The validity of the original score was assessed using Cox regression, and a modified index incorporating RTB was developed by comparing the accuracy, sensitivity, specificity, F1-score, and AUC parameters., Results: GPA categories showed an association with survival: age ( p < 0.001, hazard ratio (HR) 2.9, 95% confidence interval (CI) 2.5-3.3), Karnofsky performance status (KPS) ( p < 0.001, HR 1.3, 95% CI 1.2-1.5), number of BMs ( p = 0.019, HR 1.4, 95% CI 1.1-1.8), and the presence of extracranial manifestation ( p < 0.001, HR 3, 95% CI 1.6-2.5). The median survival for GPA 0-1 was 4 months; for GPA 1.5-2, it was 12 months; for GPA 2.5-3, it was 21 months; and for GPA 3.5-4, it was 38 months ( p < 0.001). RTB was identified as an independent prognostic factor. A cut-off of 2 cm 3 was used for further analysis, which showed a median survival of 6 months (95% CI 4-8) vs. 13 months (95% CI 11-14, p < 0.001) for patients with RTB > 2 cm 3 and <2 cm 3 , respectively. RTB was added as an additional component for a modified volumetric GPA score. The survival rates with the modified GPA score were: GPA 0-1: 4 months, GPA 1.5-2: 7 months, GPA 2.5-3: 18 months, and GPA 3.5-4: 34 months. Both scores showed good stratification, with the new score showed a trend towards better discrimination in patients with more favorable prognoses., Conclusion: The prognostic value of the original GPA was confirmed in our cohort of patients who underwent surgery for BM. The RTB was identified as a parameter of high prognostic significance and was incorporated into an updated "volumetric GPA". This score provides a novel tool for prognosis and clinical decision making in patients undergoing surgery. This method may be useful for stratification and patient selection for further treatment and in future clinical trials.

Introduction: Many patients with high-grade gliomas (HGG) are of older age., Research Question: We hypothesize that pre- and intraoperative mapping and monitoring preserve functional status in elderly patients while gross total resection (GTR) is the aim, resulting in overall survival (OS) rates comparable to the general population with HGG., Material and Methods: We subdivided a prospective cohort of 168 patients above 65 years with eloquent high-grade gliomas into four groups ([years/cases] 1: 65-69/58; 2: 70-74/47; 3: 75-79/43; 4: >79/20). All patients underwent preoperative noninvasive mapping, which was also used for decision-making, intraoperative neuromonitoring in 138 cases, direct cortical and/or subcortical motor mapping in 66 and 50 cases, and awake language mapping in 11 cases., Results: GTR and subtotal resection (STR) could be achieved in 65% and 28%, respectively. Stereotactic biopsy was performed in 8% of cases. Postoperatively, we found transient and permanent functional deficits in 13% and 11% of cases. Postoperative Karnofsky Performance Scale (KPS) did not differ between subgroups. Patients with long-term follow-up (51%) had a progression-free survival of 5.5 (1-47) months and an overall survival of 10.5 (0-86) months., Discussion and Conclusion: The interdisciplinary glioma treatment in the elderly is less age-dependent but must be adjusted to the functional status. Function-guided surgical resections could be performed as usual, with maximal tumor resection being the primary goal. However, less network capacity in the elderly to compensate for deficits might cause higher rates of permanent deficits in this group of patients with more fast-growing malignant gliomas., (© 2024 The Authors.)

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1-EPVS, 9 for Task 2-Microbleeds and 6 for Task 3-Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1-EPVS and Task 2-Microbleeds and not practically useful results yet for Task 3-Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carole H Sudre reports financial support was provided by Alzheimer’s Society. Marleen de Bruijne reports financial support was provided by Netherlands Organisation for Scientific Research. Kimberlin van Wijnen reports financial support was provided by Netherlands Organisation for Scientific Research. Shuai Chen reports financial support was provided by Netherlands Organisation for Scientific Research. Silvia Ingala, Luigi Lorenzini, Frederik Barkhof reports financial support was provided by EU Framework Horizon 2020 Research and Innovation. Florian Kofler, Bjoern Menze, Benedikt Wiestler reports financial support was provided by Deutsche Forschung Gemeinschaft. Hugo J Kuijf reports financial support was provided by Galen and Hilary Weston Foundation. Juan Domingo Gispert reports financial support was provided by Spanish Ministry of Science and Innovation. Bjoern Menze reports financial support was provided by Helmut Horten Foundation. Florian Dubost reports financial support was provided by Netherlands Organisation for Health Research and Development. Ivan Ezhov reports financial support was provided by DComEx. Marius de Groot reports a relationship with GlaxoSmithKline that includes: employment and equity or stocks. Jose Luis Molinuevo reports a relationship with Lundbeck that includes: employment. Jose Luis Molinuevo reports a relationship with Roche Diagnostics that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Genentech Inc that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Novartis that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Oryzon Genomics, S.A. that includes: board membership, consulting or advisory, and speaking and lecture fees. Juan Domingo Gispert reports a relationship with GE Healthcare that includes: funding grants. Juan Domingo Gispert reports a relationship with Roche Diagnostics that includes: funding grants. Juan Domingo Gispert reports a relationship with Hoffmann-La Roche Limited that includes: funding grants. Juan Domingo Gispert reports a relationship with Biogen that includes: speaking and lecture fees. Juan Domingo Gispert reports a relationship with Philips that includes: speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Lilly that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Green Valley that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Janssen that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with MSD that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Alector that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with BioCross that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with Eisai that includes: board membership, consulting or advisory, and speaking and lecture fees. Jose Luis Molinuevo reports a relationship with ProMIS Neurosciences Inc that includes: board membership, consulting or advisory, and speaking and lecture fees. NVIDIA and Icometrix provided the challenge prizes., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice., Objective: We performed a systematic review and meta-analysis on the use of QSM in MS., Methods: Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively., Results: After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I 2  = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I 2  = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I 2  = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I 2  = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I 2  = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions., Conclusions: We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: GM pathology plays an essential role in MS disability progression, emphasizing the importance of neuroradiologic biomarkers to capture the heterogeneity of cortical disease burden. This study aimed to assess the validity of a patch-wise, individual interpretation of cortical thickness data to identify GM pathology, the "mosaic approach," which was previously suggested as a biomarker for assessing and localizing atrophy., Materials and Methods: We investigated the mosaic approach in a cohort of 501 patients with MS with respect to 89 internal and 651 external controls. The resulting metric of the mosaic approach is the so-called thin patch fraction, which is an estimate of overall cortical disease burden per patient. We evaluated the mosaic approach with respect to the following: 1) discrimination between patients with MS and controls, 2) classification between different MS phenotypes, and 3) association with established biomarkers reflecting MS disease burden, using general linear modeling., Results: The thin patch fraction varied significantly between patients with MS and healthy controls and discriminated among MS phenotypes. Furthermore, the thin patch fraction was associated with disease burden, including the Expanded Disability Status Scale, cognitive and fatigue scores, and lesion volume., Conclusions: This study demonstrates the validity of the mosaic approach as a neuroradiologic biomarker in MS. The output of the mosaic approach, namely the thin patch fraction, is a candidate biomarker for assessing and localizing cortical GM pathology. The mosaic approach can furthermore enhance the development of a personalized cortical MS biomarker, given that the thin patch fraction provides a feature on which artificial intelligence methods can be trained. Most important, we showed the validity of the mosaic approach when referencing data with respect to external control MR imaging repositories., (© 2024 by American Journal of Neuroradiology.)

Background: The diffuse growth pattern of glioblastoma is one of the main challenges for accurate treatment. Computational tumor growth modeling has emerged as a promising tool to guide personalized therapy. Here, we performed clinical and biological validation of a novel growth model, aiming to close the gap between the experimental state and clinical implementation., Methods: One hundred and twenty-four patients from The Cancer Genome Archive (TCGA) and 397 patients from the UCSF Glioma Dataset were assessed for significant correlations between clinical data, genetic pathway activation maps (generated with PARADIGM; TCGA only), and infiltration ( D w ) as well as proliferation (ρ) parameters stemming from a Fisher-Kolmogorov growth model. To further evaluate clinical potential, we performed the same growth modeling on preoperative magnetic resonance imaging data from 30 patients of our institution and compared model-derived tumor volume and recurrence coverage with standard radiotherapy plans., Results: The parameter ratio D w /ρ ( P  < .05 in TCGA) as well as the simulated tumor volume ( P  < .05 in TCGA/UCSF) were significantly inversely correlated with overall survival. Interestingly, we found a significant correlation between 11 proliferation pathways and the estimated proliferation parameter. Depending on the cutoff value for tumor cell density, we observed a significant improvement in recurrence coverage without significantly increased radiation volume utilizing model-derived target volumes instead of standard radiation plans., Conclusions: Identifying a significant correlation between computed growth parameters and clinical and biological data, we highlight the potential of tumor growth modeling for individualized therapy of glioblastoma. This might improve the accuracy of radiation planning in the near future., Competing Interests: M.M. and F.S. serve as part-time consultants for Novocure GmbH., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)