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Protocol of the observational study STRATUM-OS: First step in the development and validation of the STRATUM tool based on multimodal data processing to assist surgery in patients affected by intra-axial brain tumours

Fabelo, H., Ramallo-Farina, Y., Morera, J., Pineiro, J. F., Lagares, A., Jimenez-Roldan, L., Burstrom, G., Garcia-Bello, M. A., Garcia-Perez, L., Falero, R., Gonzalez, M., Duque, S., Rodriguez-Jimenez, C., Hernandez, M., Delgado-Sanchez, J. J., Paredes, A. B., Hernandez, G., Ponce, P., Leon, R., Gonzalez-Martin, J. M., Rodriguez-Esparragon, F., Callico, G. M., Wagner, A. M., Clavo, B., STRATUM,

medrxiv logopreprintJun 13 2025
IntroductionIntegrated digital diagnostics can support complex surgeries in many anatomic sites, and brain tumour surgery represents one of the most complex cases. Neurosurgeons face several challenges during brain tumour surgeries, such as differentiating critical tissue from brain tumour margins. To overcome these challenges, the STRATUM project will develop a 3D decision support tool for brain surgery guidance and diagnostics based on multimodal data processing, including hyperspectral imaging, integrated as a point-of-care computing tool in neurosurgical workflows. This paper reports the protocol for the development and technical validation of the STRATUM tool. Methods and analysisThis international multicentre, prospective, open, observational cohort study, STRATUM-OS (study: 28 months, pre-recruitment: 2 months, recruitment: 20 months, follow-up: 6 months), with no control group, will collect data from 320 patients undergoing standard neurosurgical procedures to: (1) develop and technically validate the STRATUM tool, and (2) collect the outcome measures for comparing the standard procedure versus the standard procedure plus the use of the STRATUM tool during surgery in a subsequent historically controlled non-randomized clinical trial. Ethics and disseminationThe protocol was approved by the participant Ethics Committees. Results will be disseminated in scientific conferences and peer-reviewed journals. Trial registration number[Pending Number] ARTICLE SUMMARYO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LISTRATUM-OS will be the first multicentre prospective observational study to develop and technically validate a 3D decision support tool for brain surgery guidance and diagnostics in real-time based on artificial intelligence and multimodal data processing, including the emerging hyperspectral imaging modality. C_LIO_LIThis study encompasses a prospective collection of multimodal pre, intra and postoperative medical data, including innovative imaging modalities, from patients with intra-axial brain tumours. C_LIO_LIThis large observational study will act as historical control in a subsequent clinical trial to evaluate a fully-working prototype. C_LIO_LIAlthough the estimated sample size is deemed adequate for the purpose of the study, the complexity of the clinical context and the type of surgery could potentially lead to under-recruitment and under-representation of less prevalent tumour types. C_LI

Deep-Learning Based Contrast Boosting Improves Lesion Visualization and Image Quality: A Multi-Center Multi-Reader Study on Clinical Performance with Standard Contrast Enhanced MRI of Brain Tumors

Pasumarthi, S., Campbell Arnold, T., Colombo, S., Rudie, J. D., Andre, J. B., Elor, R., Gulaka, P., Shankaranarayanan, A., Erb, G., Zaharchuk, G.

medrxiv logopreprintJun 13 2025
BackgroundGadolinium-based Contrast Agents (GBCAs) are used in brain MRI exams to improve the visualization of pathology and improve the delineation of lesions. Higher doses of GBCAs can improve lesion sensitivity but involve substantial deviation from standard-of-care procedures and may have safety implications, particularly in the light of recent findings on gadolinium retention and deposition. PurposeTo evaluate the clinical performance of an FDA cleared deep-learning (DL) based contrast boosting algorithm in routine clinical brain MRI exams. MethodsA multi-center retrospective database of contrast-enhanced brain MRI images (obtained from April 2017 to December 2023) was used to evaluate a DL-based contrast boosting algorithm. Pre-contrast and standard post-contrast (SC) images were processed with the algorithm to obtain contrast boosted (CB) images. Quantitative performance of CB images in comparison to SC images was compared using contrast-to-noise ratio (CNR), lesion-to-brain ratio (LBR) and contrast enhancement percentage (CEP). Three board-certified radiologists reviewed CB and SC images side-by-side for qualitative evaluation and rated them on a 4-point Likert scale for lesion contrast enhancement, border delineation, internal morphology, overall image quality, presence of artefacts, and changes in vessel conspicuity. The presence, cause, and severity of any false lesions was recorded. CB results were compared to SC using Wilcoxon signed rank test for statistical significance. ResultsBrain MRI images from 110 patients (47 {+/-} 22 years; 52 Females, 47 Males, 11 N/A) were evaluated. CB images had superior quantitative performance than SC images in terms of CNR (+634%), LBR (+70%) and CEP (+150%). In the qualitative assessment CB images showed better lesion visualization (3.73 vs 3.16) and had better image quality (3.55 vs 3.07). Readers were able to rule out all false lesions on CB by using SC for comparison. ConclusionsDeep learning based contrast boosting improves lesion visualization and image quality without increasing contrast dosage. Key ResultsO_LIIn a retrospective study of 110 patients, deep-learning based contrast boosted (CB) images showed better lesion visualization than standard post-contrast (SC) brain MRI images (3.73 vs 3.16; mean reader scores [4-point Likert scale]) C_LIO_LICB images had better overall image quality than SC images (3.55 vs 3.07) C_LIO_LIContrast-to-noise ratio, Lesion-to-brain Ratio and Contrast Enhancement Percentage for CB images were significantly higher than SC images (+729%, +88% and +165%; p < 0.001) C_LI Summary StatementDeep-learning based contrast boosting achieves better lesion visualization and overall image quality and provides more contrast information, without increasing the contrast dosage in contrast-enhanced brain MR protocols.

BraTS orchestrator : Democratizing and Disseminating state-of-the-art brain tumor image analysis

Florian Kofler, Marcel Rosier, Mehdi Astaraki, Ujjwal Baid, Hendrik Möller, Josef A. Buchner, Felix Steinbauer, Eva Oswald, Ezequiel de la Rosa, Ivan Ezhov, Constantin von See, Jan Kirschke, Anton Schmick, Sarthak Pati, Akis Linardos, Carla Pitarch, Sanyukta Adap, Jeffrey Rudie, Maria Correia de Verdier, Rachit Saluja, Evan Calabrese, Dominic LaBella, Mariam Aboian, Ahmed W. Moawad, Nazanin Maleki, Udunna Anazodo, Maruf Adewole, Marius George Linguraru, Anahita Fathi Kazerooni, Zhifan Jiang, Gian Marco Conte, Hongwei Li, Juan Eugenio Iglesias, Spyridon Bakas, Benedikt Wiestler, Marie Piraud, Bjoern Menze

arxiv logopreprintJun 13 2025
The Brain Tumor Segmentation (BraTS) cluster of challenges has significantly advanced brain tumor image analysis by providing large, curated datasets and addressing clinically relevant tasks. However, despite its success and popularity, algorithms and models developed through BraTS have seen limited adoption in both scientific and clinical communities. To accelerate their dissemination, we introduce BraTS orchestrator, an open-source Python package that provides seamless access to state-of-the-art segmentation and synthesis algorithms for diverse brain tumors from the BraTS challenge ecosystem. Available on GitHub (https://github.com/BrainLesion/BraTS), the package features intuitive tutorials designed for users with minimal programming experience, enabling both researchers and clinicians to easily deploy winning BraTS algorithms for inference. By abstracting the complexities of modern deep learning, BraTS orchestrator democratizes access to the specialized knowledge developed within the BraTS community, making these advances readily available to broader neuro-radiology and neuro-oncology audiences.

Recent Advances in sMRI and Artificial Intelligence for Presurgical Planning in Focal Cortical Dysplasia: A Systematic Review.

Mahmoudi A, Alizadeh A, Ganji Z, Zare H

pubmed logopapersJun 13 2025
Focal Cortical Dysplasia (FCD) is a leading cause of drug-resistant epilepsy, particularly in children and young adults, necessitating precise presurgical planning. Traditional structural MRI often fails to detect subtle FCD lesions, especially in MRI-negative cases. Recent advancements in Artificial Intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), have the potential to enhance FCD detection's sensitivity and specificity. This systematic review, following PRISMA guidelines, searched PubMed, Embase, Scopus, Web of Science, and Science Direct for articles published from 2020 onwards, using keywords related to "Focal Cortical Dysplasia," "MRI," and "Artificial Intelligence/Machine Learning/Deep Learning." Included were original studies employing AI and structural MRI (sMRI) for FCD detection in humans, reporting quantitative performance metrics, and published in English. Data extraction was performed independently by two reviewers, with discrepancies resolved by a third. The included studies demonstrated that AI significantly improved FCD detection, achieving sensitivity up to 97.1% and specificities up to 84.3% across various MRI sequences, including MPRAGE, MP2RAGE, and FLAIR. AI models, particularly deep learning models, matched or surpassed human radiologist performance, with combined AI-human expertise reaching up to 87% detection rates. Among 88 full-text articles reviewed, 27 met inclusion criteria. The studies emphasized the importance of advanced MRI sequences and multimodal MRI for enhanced detection, though model performance varied with FCD type and training datasets. Recent advances in sMRI and AI, especially deep learning, offer substantial potential to improve FCD detection, leading to better presurgical planning and patient outcomes in drug-resistant epilepsy. These methods enable faster, more accurate, and automated FCD detection, potentially enhancing surgical decision-making. Further clinical validation and optimization of AI algorithms across diverse datasets are essential for broader clinical translation.

Prediction of functional outcome after traumatic brain injury: a narrative review.

Iaquaniello C, Scordo E, Robba C

pubmed logopapersJun 13 2025
To synthesize current evidence on prognostic factors, tools, and strategies influencing functional outcomes in patients with traumatic brain injury (TBI), with a focus on the acute and postacute phases of care. Key early predictors such as Glasgow Coma Scale (GCS) scores, pupillary reactivity, and computed tomography (CT) imaging findings remain fundamental in guiding clinical decision-making. Prognostic models like IMPACT and CRASH enhance early risk stratification, while outcome measures such as the Glasgow Outcome Scale-Extended (GOS-E) provide structured long-term assessments. Despite their utility, heterogeneity in assessment approaches and treatment protocols continues to limit consistency in outcome predictions. Recent advancements highlight the value of fluid biomarkers like neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP), which offer promising avenues for improved accuracy. Additionally, artificial intelligence models are emerging as powerful tools to integrate complex datasets and refine individualized outcome forecasting. Neurological prognostication after TBI is evolving through the integration of clinical, radiological, molecular, and computational data. Although standardized models and scales remain foundational, emerging technologies and therapies - such as biomarkers, machine learning, and neurostimulants - represent a shift toward more personalized and actionable strategies to optimize recovery and long-term function.

Does restrictive anorexia nervosa impact brain aging? A machine learning approach to estimate age based on brain structure.

Gupta Y, de la Cruz F, Rieger K, di Giuliano M, Gaser C, Cole J, Breithaupt L, Holsen LM, Eddy KT, Thomas JJ, Cetin-Karayumak S, Kubicki M, Lawson EA, Miller KK, Misra M, Schumann A, Bär KJ

pubmed logopapersJun 13 2025
Anorexia nervosa (AN), a severe eating disorder marked by extreme weight loss and malnutrition, leads to significant alterations in brain structure. This study used machine learning (ML) to estimate brain age from structural MRI scans and investigated brain-predicted age difference (brain-PAD) as a potential biomarker in AN. Structural MRI scans were collected from female participants aged 10-40 years across two institutions (Boston, USA, and Jena, Germany), including acute AN (acAN; n=113), weight-restored AN (wrAN; n=35), and age-matched healthy controls (HC; n=90). The ML model was trained on 3487 healthy female participants (ages 5-45 years) from ten datasets, using 377 neuroanatomical features extracted from T1-weighted MRI scans. The model achieved strong performance with a mean absolute error (MAE) of 1.93 years and a correlation of r = 0.88 in HCs. In acAN patients, brain age was overestimated by an average of +2.25 years, suggesting advanced brain aging. In contrast, wrAN participants showed significantly lower brain-PAD than acAN (+0.26 years, p=0.0026) and did not differ from HC (p=0.98), suggesting normalization of brain age estimates following weight restoration. A significant group-by-age interaction effect on predicted brain age (p<0.001) indicated that brain age deviations were most pronounced in younger acAN participants. Brain-PAD in acAN was significantly negatively associated with BMI (r = -0.291, p<sub>fdr</sub> = 0.005), but not in wrAN or HC groups. Importantly, no significant associations were found between brain-PAD and clinical symptom severity. These findings suggest that acute AN is linked to advanced brain aging during the acute stage, and that may partially normalize following weight recovery.

Prediction of NIHSS Scores and Acute Ischemic Stroke Severity Using a Cross-attention Vision Transformer Model with Multimodal MRI.

Tuxunjiang P, Huang C, Zhou Z, Zhao W, Han B, Tan W, Wang J, Kukun H, Zhao W, Xu R, Aihemaiti A, Subi Y, Zou J, Xie C, Chang Y, Wang Y

pubmed logopapersJun 13 2025
This study aimed to develop and evaluate models for classifying the severity of neurological impairment in acute ischemic stroke (AIS) patients using multimodal MRI data. A retrospective cohort of 1227 AIS patients was collected and categorized into mild (NIHSS<5) and moderate-to-severe (NIHSS≥5) stroke groups based on NIHSS scores. Eight baseline models were constructed for performance comparison, including a clinical model, radiomics models using DWI or multiple MRI sequences, and deep learning (DL) models with varying fusion strategies (early fusion, later fusion, full cross-fusion, and DWI-centered cross-fusion). All DL models were based on the Vision Transformer (ViT) framework. Model performance was evaluated using metrics such as AUC and ACC, and robustness was assessed through subgroup analyses and visualization using Grad-CAM. Among the eight models, the DL model using DWI as the primary sequence with cross-fusion of other MRI sequences (Model 8) achieved the best performance. In the test cohort, Model 8 demonstrated an AUC of 0.914, ACC of 0.830, and high specificity (0.818) and sensitivity (0.853). Subgroup analysis shows that model 8 is robust in most subgroups with no significant prediction difference (p > 0.05), and the AUC value consistently exceeds 0.900. A significant predictive difference was observed in the BMI group (p < 0.001). The results of external validation showed that the AUC values of the model 8 in center 2 and center 3 reached 0.910 and 0.912, respectively. Visualization using Grad-CAM emphasized the infarct core as the most critical region contributing to predictions, with consistent feature attention across DWI, T1WI, T2WI, and FLAIR sequences, further validating the interpretability of the model. A ViT-based DL model with cross-modal fusion strategies provides a non-invasive and efficient tool for classifying AIS severity. Its robust performance across subgroups and interpretability make it a promising tool for personalized management and decision-making in clinical practice.

SWDL: Stratum-Wise Difference Learning with Deep Laplacian Pyramid for Semi-Supervised 3D Intracranial Hemorrhage Segmentation

Cheng Wang, Siqi Chen, Donghua Mi, Yang Chen, Yudong Zhang, Yinsheng Li

arxiv logopreprintJun 12 2025
Recent advances in medical imaging have established deep learning-based segmentation as the predominant approach, though it typically requires large amounts of manually annotated data. However, obtaining annotations for intracranial hemorrhage (ICH) remains particularly challenging due to the tedious and costly labeling process. Semi-supervised learning (SSL) has emerged as a promising solution to address the scarcity of labeled data, especially in volumetric medical image segmentation. Unlike conventional SSL methods that primarily focus on high-confidence pseudo-labels or consistency regularization, we propose SWDL-Net, a novel SSL framework that exploits the complementary advantages of Laplacian pyramid and deep convolutional upsampling. The Laplacian pyramid excels at edge sharpening, while deep convolutions enhance detail precision through flexible feature mapping. Our framework achieves superior segmentation of lesion details and boundaries through a difference learning mechanism that effectively integrates these complementary approaches. Extensive experiments on a 271-case ICH dataset and public benchmarks demonstrate that SWDL-Net outperforms current state-of-the-art methods in scenarios with only 2% labeled data. Additional evaluations on the publicly available Brain Hemorrhage Segmentation Dataset (BHSD) with 5% labeled data further confirm the superiority of our approach. Code and data have been released at https://github.com/SIAT-CT-LAB/SWDL.

Score-based Generative Diffusion Models to Synthesize Full-dose FDG Brain PET from MRI in Epilepsy Patients

Jiaqi Wu, Jiahong Ouyang, Farshad Moradi, Mohammad Mehdi Khalighi, Greg Zaharchuk

arxiv logopreprintJun 12 2025
Fluorodeoxyglucose (FDG) PET to evaluate patients with epilepsy is one of the most common applications for simultaneous PET/MRI, given the need to image both brain structure and metabolism, but is suboptimal due to the radiation dose in this young population. Little work has been done synthesizing diagnostic quality PET images from MRI data or MRI data with ultralow-dose PET using advanced generative AI methods, such as diffusion models, with attention to clinical evaluations tailored for the epilepsy population. Here we compared the performance of diffusion- and non-diffusion-based deep learning models for the MRI-to-PET image translation task for epilepsy imaging using simultaneous PET/MRI in 52 subjects (40 train/2 validate/10 hold-out test). We tested three different models: 2 score-based generative diffusion models (SGM-Karras Diffusion [SGM-KD] and SGM-variance preserving [SGM-VP]) and a Transformer-Unet. We report results on standard image processing metrics as well as clinically relevant metrics, including congruency measures (Congruence Index and Congruency Mean Absolute Error) that assess hemispheric metabolic asymmetry, which is a key part of the clinical analysis of these images. The SGM-KD produced the best qualitative and quantitative results when synthesizing PET purely from T1w and T2 FLAIR images with the least mean absolute error in whole-brain specific uptake value ratio (SUVR) and highest intraclass correlation coefficient. When 1% low-dose PET images are included in the inputs, all models improve significantly and are interchangeable for quantitative performance and visual quality. In summary, SGMs hold great potential for pure MRI-to-PET translation, while all 3 model types can synthesize full-dose FDG-PET accurately using MRI and ultralow-dose PET.

NeuroEmo: A neuroimaging-based fMRI dataset to extract temporal affective brain dynamics for Indian movie video clips stimuli using dynamic functional connectivity approach with graph convolution neural network (DFC-GCNN).

Abgeena A, Garg S, Goyal N, P C JR

pubmed logopapersJun 12 2025
FMRI, a non-invasive neuroimaging technique, can detect emotional brain activation patterns. It allows researchers to observe functional changes in the brain, making it a valuable tool for emotion recognition. For improved emotion recognition systems, it becomes crucial to understand the neural mechanisms behind emotional processing in the brain. There have been multiple studies across the world on the same, however, research on fMRI-based emotion recognition within the Indian population remains scarce, limiting the generalizability of existing models. To address this gap, a culturally relevant neuroimaging dataset has been created https://openneuro.org/datasets/ds005700 for identifying five emotional states i.e., calm, afraid, delighted, depressed and excited-in a diverse group of Indian participants. To ensure cultural relevance, emotional stimuli were derived from Bollywood movie clips. This study outlines the fMRI task design, experimental setup, data collection procedures, preprocessing steps, statistical analysis using the General Linear Model (GLM), and region-of-interest (ROI)-based dynamic functional connectivity (DFC) extraction using parcellation based on the Power et al. (2011) functional atlas. A supervised emotion classification model has been proposed using a Graph Convolutional Neural Network (GCNN), where graph structures were constructed from DFC matrices at varying thresholds. The DFC-GCNN model achieved an impressive 95% classification accuracy across 5-fold cross-validation, highlighting emotion-specific connectivity dynamics in key affective regions, including the amygdala, prefrontal cortex, and anterior insula. These findings emphasize the significance of temporal variability in emotional state classification. By introducing a culturally specific neuroimaging dataset and a GCNN-based emotion recognition framework, this research enhances the applicability of graph-based models for identifying region-wise connectivity patterns in fMRI data. It also offers novel insights into cross-cultural differences in emotional processing at the neural level. Furthermore, the high spatial and temporal resolution of the fMRI dataset provides a valuable resource for future studies in emotional neuroscience and related disciplines.
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