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Multivariate whole brain neurodegenerative-cognitive-clinical severity mapping in the Alzheimer's disease continuum using explainable AI

Murad, T., Miao, H., Thakuri, D. S., Darekar, G., Chand, G.

medrxiv logopreprintJul 11 2025
Neurodegeneration and cognitive impairment are commonly reported in Alzheimers disease (AD); however, their multivariate links are not well understood. To map the multivariate relationships between whole brain neurodegenerative (WBN) markers, global cognition, and clinical severity in the AD continuum, we developed the explainable artificial intelligence (AI) methods, validated on semi-simulated data, and applied the outperforming method systematically to large-scale experimental data (N=1,756). The outperforming explainable AI method showed robust performance in predicting cognition from regional WBN markers and identified the ground-truth simulated dominant brain regions contributing to cognition. This method also showed excellent performance on experimental data and identified several prominent WBN regions hierarchically and simultaneously associated with cognitive declines across the AD continuum. These multivariate regional features also correlated with clinical severity, suggesting their clinical relevance. Overall, this study innovatively mapped the multivariate regional WBN-cognitive-clinical severity relationships in the AD continuum, thereby significantly advancing AD-relevant neurobiological pathways.

Automated MRI protocoling in neuroradiology in the era of large language models.

Reiner LN, Chelbi M, Fetscher L, Stöckel JC, Csapó-Schmidt C, Guseynova S, Al Mohamad F, Bressem KK, Nawabi J, Siebert E, Wattjes MP, Scheel M, Meddeb A

pubmed logopapersJul 11 2025
This study investigates the automation of MRI protocoling, a routine task in radiology, using large language models (LLMs), comparing an open-source (LLama 3.1 405B) and a proprietary model (GPT-4o) with and without retrieval-augmented generation (RAG), a method for incorporating domain-specific knowledge. This retrospective study included MRI studies conducted between January and December 2023, along with institution-specific protocol assignment guidelines. Clinical questions were extracted, and a neuroradiologist established the gold standard protocol. LLMs were tasked with assigning MRI protocols and contrast medium administration with and without RAG. The results were compared to protocols selected by four radiologists. Token-based symmetric accuracy, the Wilcoxon signed-rank test, and the McNemar test were used for evaluation. Data from 100 neuroradiology reports (mean age = 54.2 years ± 18.41, women 50%) were included. RAG integration significantly improved accuracy in sequence and contrast media prediction for LLama 3.1 (Sequences: 38% vs. 70%, P < .001, Contrast Media: 77% vs. 94%, P < .001), and GPT-4o (Sequences: 43% vs. 81%, P < .001, Contrast Media: 79% vs. 92%, P = .006). GPT-4o outperformed LLama 3.1 in MRI sequence prediction (81% vs. 70%, P < .001), with comparable accuracies to the radiologists (81% ± 0.21, P = .43). Both models equaled radiologists in predicting contrast media administration (LLama 3.1 RAG: 94% vs. 91% ± 0.2, P = .37, GPT-4o RAG: 92% vs. 91% ± 0.24, P = .48). Large language models show great potential as decision-support tools for MRI protocoling, with performance similar to radiologists. RAG enhances the ability of LLMs to provide accurate, institution-specific protocol recommendations.

F3-Net: Foundation Model for Full Abnormality Segmentation of Medical Images with Flexible Input Modality Requirement

Seyedeh Sahar Taheri Otaghsara, Reza Rahmanzadeh

arxiv logopreprintJul 11 2025
F3-Net is a foundation model designed to overcome persistent challenges in clinical medical image segmentation, including reliance on complete multimodal inputs, limited generalizability, and narrow task specificity. Through flexible synthetic modality training, F3-Net maintains robust performance even in the presence of missing MRI sequences, leveraging a zero-image strategy to substitute absent modalities without relying on explicit synthesis networks, thereby enhancing real-world applicability. Its unified architecture supports multi-pathology segmentation across glioma, metastasis, stroke, and white matter lesions without retraining, outperforming CNN-based and transformer-based models that typically require disease-specific fine-tuning. Evaluated on diverse datasets such as BraTS 2021, BraTS 2024, and ISLES 2022, F3-Net demonstrates strong resilience to domain shifts and clinical heterogeneity. On the whole pathology dataset, F3-Net achieves average Dice Similarity Coefficients (DSCs) of 0.94 for BraTS-GLI 2024, 0.82 for BraTS-MET 2024, 0.94 for BraTS 2021, and 0.79 for ISLES 2022. This positions it as a versatile, scalable solution bridging the gap between deep learning research and practical clinical deployment.

Advancing Rare Neurological Disorder Diagnosis: Addressing Challenges with Systematic Reviews and AI-Driven MRI Meta-Trans Learning Framework for NeuroDegenerative Disorders.

Gupta A, Malhotra D

pubmed logopapersJul 11 2025
Neurological Disorders (ND) affect a large portion of the global population, impacting the brain, spinal cord, and nerves. These disorders fall into categories such as NeuroDevelopmental (NDD), NeuroBiological (NBD), and NeuroDegenerative (ND<sub>e</sub>) disorders, which range from common to rare conditions. While Artificial Intelligence (AI) has advanced healthcare diagnostics, training Machine Learning (ML) and Deep Learning (DL) models for early detection of rare neurological disorders remains a challenge due to limited patient data. This data scarcity poses a significant public health issue. Meta_Trans Learning (M<sub>TA</sub>L), which integrates Meta-Learning (M<sub>t</sub>L) and Transfer Learning (TL), offers a promising solution by leveraging small datasets to extract expert patterns, generalize findings, and reduce AI bias in healthcare. This research systematically reviews studies from 2018 to 2024 to explore how ML and M<sub>TA</sub>L techniques are applied in diagnosing NDD, NBD, and ND<sub>e</sub> disorders. It also provides statistical and parametric analysis of ML and DL methods for neurological disorder diagnosis. Lastly, the study introduces a MRI-based ND<sub>e</sub>-M<sub>TA</sub>L framework to aid healthcare professionals in early detection of rare neuro disorders, aiming to enhance diagnostic accuracy and advance healthcare practices.

CSCE: Cross Supervising and Confidence Enhancement pseudo-labels for semi-supervised subcortical brain structure segmentation.

Sui Y, Zhang Y, Liu C

pubmed logopapersJul 11 2025
Robust and accurate segmentation of subcortical structures in brain MR images lays the foundation for observation, analysis and treatment planning of various brain diseases. Deep learning techniques based on Deep Neural Networks (DNNs) have achieved remarkable results in medical image segmentation by using abundant labeled data. However, due to the time-consuming and expensive of acquiring high quality annotations of brain subcortical structures, semi-supervised algorithms become practical in application. In this paper, we propose a novel framework for semi-supervised subcortical brain structure segmentation, based on pseudo-labels Cross Supervising and Confidence Enhancement (CSCE). Our framework comprises dual student-teacher models, specifically a U-Net and a TransUNet. For unlabeled data training, the TransUNet teacher generates pseudo-labels to supervise the U-Net student, while the U-Net teacher generates pseudo-labels to supervise the TransUNet student. This mutual supervision between the two models promotes and enhances their performance synergistically. We have designed two mechanisms to enhance the confidence of pseudo-labels to improve the reliability of cross-supervision: a) Using information entropy to describe uncertainty quantitatively; b) Design an auxiliary detection task to perform uncertainty detection on the pseudo-labels output by the teacher model, and then screened out reliable pseudo-labels for cross-supervision. Finally, we construct an end-to-end deep brain structure segmentation network only using one teacher network (U-Net or TransUNet) for inference, the segmentation results are significantly improved without increasing the parameters amount and segmentation time compared with supervised U-Net or TransUNet based segmentation algorithms. Comprehensive experiments are performed on two public benchmark brain MRI datasets. The proposed method achieves the best Dice scores and MHD values on both datasets compared to several recent state-of-the-art semi-supervised segmentation methods.

Rapid MRI-Based Synthetic CT Simulations for Precise tFUS Targeting

Hengyu Gao, Shaodong Ding, Ziyang Liu, Jiefu Zhang, Bolun Li, Zhiwu An, Li Wang, Jing Jing, Tao Liu, Yubo Fan, Zhongtao Hu

arxiv logopreprintJul 11 2025
Accurate targeting is critical for the effectiveness of transcranial focused ultrasound (tFUS) neuromodulation. While CT provides accurate skull acoustic properties, its ionizing radiation and poor soft tissue contrast limit clinical applicability. In contrast, MRI offers superior neuroanatomical visualization without radiation exposure but lacks skull property mapping. This study proposes a novel, fully CT free simulation framework that integrates MRI-derived synthetic CT (sCT) with efficient modeling techniques for rapid and precise tFUS targeting. We trained a deep-learning model to generate sCT from T1-weighted MRI and integrated it with both full-wave (k-Wave) and accelerated simulation methods, hybrid angular spectrum (kWASM) and Rayleigh-Sommerfeld ASM (RSASM). Across five skull models, both full-wave and hybrid pipelines using sCT demonstrated sub-millimeter targeting deviation, focal shape consistency (FWHM ~3.3-3.8 mm), and <0.2 normalized pressure error compared to CT-based gold standard. Notably, the kW-ASM and RS-ASM pipelines reduced simulation time from ~3320 s to 187 s and 34 s respectively, achieving ~94% and ~90% time savings. These results confirm that MRI-derived sCT combined with innovative rapid simulation techniques enables fast, accurate, and radiation-free tFUS planning, supporting its feasibility for scalable clinical applications.

Cross-Domain Identity Representation for Skull to Face Matching with Benchmark DataSet

Ravi Shankar Prasad, Dinesh Singh

arxiv logopreprintJul 11 2025
Craniofacial reconstruction in forensic science is crucial for the identification of the victims of crimes and disasters. The objective is to map a given skull to its corresponding face in a corpus of faces with known identities using recent advancements in computer vision, such as deep learning. In this paper, we presented a framework for the identification of a person given the X-ray image of a skull using convolutional Siamese networks for cross-domain identity representation. Siamese networks are twin networks that share the same architecture and can be trained to discover a feature space where nearby observations that are similar are grouped and dissimilar observations are moved apart. To do this, the network is exposed to two sets of comparable and different data. The Euclidean distance is then minimized between similar pairs and maximized between dissimilar ones. Since getting pairs of skull and face images are difficult, we prepared our own dataset of 40 volunteers whose front and side skull X-ray images and optical face images were collected. Experiments were conducted on the collected cross-domain dataset to train and validate the Siamese networks. The experimental results provide satisfactory results on the identification of a person from the given skull.

Tiny-objective segmentation for spot signs on multi-phase CT angiography via contrastive learning with dynamic-updated positive-negative memory banks.

Zhang J, Horn M, Tanaka K, Bala F, Singh N, Benali F, Ganesh A, Demchuk AM, Menon BK, Qiu W

pubmed logopapersJul 11 2025
Presence of spot sign on CT Angiography (CTA) is associated with hematoma growth in patients with intracerebral hemorrhage. Measuring spot sign volume over time may aid to predict hematoma expansion. Due to the difficulties that imaging characteristics of spot sign are similar with vein and calcification and spot signs are tiny appeared in CTA images to detect, our aim is to develop an automated method to pick up spot signs accurately. We proposed a novel collaborative architecture of network based on a student-teacher model by efficiently exploiting additional negative samples with contrastive learning. In particular, a set of dynamic-updated memory banks is proposed to learn more distinctive features from the extremely imbalanced positive and negative samples. Alongside, a two-steam network with an additional contextual-decoder is designed for learning more contextual information at different scales in a collaborative way. Besides, to better inhibit the false positive detection rate, a region restriction loss function is further designed to confine the spot sign segmentation within the hemorrhage. Quantitative evaluations using dice, volume correlation, sensitivity, specificity, area under the curve show that the proposed method is able to segment and detect spot signs accurately. Our proposed contractive learning framework obtained the best segmentation performance regarding a mean Dice of 0.638 ± 0211, a mean VC of 0.871 and a mean VDP of 0.348 ± 0.237 and detection performance regarding sensitivity of 0.956 with CI(0.895,1.000), specificity of 0.833 with CI(0.766,0.900), and AUC of 0.892 with CI(0.888,0.896), outperforming nnuNet, cascade-nnuNet, nnuNet++, SegRegNet, UNETR and SwinUNETR. This paper proposed a novel segmentation approach that leverages contrastive learning to explore additional negative samples concurrently for the automatic segmentation of spot signs on mCTA images. The experimental results demonstrate the effectiveness of our method and highlight its potential applicability in clinical settings for measuring spot sign volumes.

The potential of machine learning to personalized medicine in Neurogenetics: Current trends and future directions.

Ghorbian M, Ghorbian S

pubmed logopapersJul 10 2025
Neurogenetic disorders (NeD) are a group of neurological conditions resulting from inherited genetic defects. By affecting the normal functioning of the nervous system, these diseases lead to serious problems in movement, cognition, and other body functions. In recent years, machine learning (ML) approaches have proven highly effective, enabling the analysis and processing of vast amounts of medical data. By analyzing genetic data, medical imaging, and other clinical data, these techniques can contribute to early diagnosis and more effective treatment of NeD. However, using these approaches is challenged by issues including data variability, model explainability, and the requirement for interdisciplinary collaboration. This paper investigates the impact of ML on healthcare diagnosis and care of common NeD, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Multiple Sclerosis disease (MSD). The purpose of this research is to determine the opportunities and challenges of using these techniques in the field of neurogenetic medicine. Our findings show that using ML can increase the detection accuracy by 85 % and reduce the detection time by 60 %. Additionally, the use of these techniques in predicting patient prognosis has been 70 % more accurate than traditional methods. Ultimately, this research will enable medical professionals and researchers to leverage ML approaches in advancing the diagnostic and therapeutic processes of NeD by identifying the opportunities and challenges.

A deep learning-based clinical decision support system for glioma grading using ensemble learning and knowledge distillation.

Liu Y, Shi Z, Xiao C, Wang B

pubmed logopapersJul 10 2025
Gliomas are the most common malignant primary brain tumors, and grading their severity, particularly the diagnosis of low-grade gliomas, remains a challenging task for clinicians and radiologists. With advancements in deep learning and medical image processing technologies, the development of Clinical Decision Support Systems (CDSS) for glioma grading offers significant benefits for clinical treatment. This study proposes a CDSS for glioma grading, integrating a novel feature extraction framework. The method is based on combining ensemble learning and knowledge distillation: teacher models were constructed through ensemble learning, while uncertainty-weighted ensemble averaging is applied during student model training to refine knowledge transfer. This approach bridges the teacher-student performance gap, enhancing grading accuracy, reliability, and clinical applicability with lightweight deployment. Experimental results show 85.96 % Accuracy (5.2 % improvement over baseline), with Precision (83.90 %), Recall (87.40 %), and F1-score (83.90 %) increasing by 7.5 %, 5.1 %, and 5.1 % respectively. The teacher-student performance gap is reduced to 3.2 %, confirming effectiveness. Furthermore, the developed CDSS not only ensures rapid and accurate glioma grading but also includes critical features influencing the grading results, seamlessly integrating a methodology for generating comprehensive diagnostic reports. Consequently, the glioma grading CDSS represents a practical clinical decision support tool capable of delivering accurate and efficient auxiliary diagnostic decisions for physicians and patients.
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