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Multimodal Integration of Plasma, MRI, and Genetic Risk for Cerebral Amyloid Prediction

yichen, w., Chen, H., yuxin, C., Yuyan, C., shiyun, Z., Kexin, W., Yidong, J., Tianyu, B., Yanxi, H., MingKai, Z., Chengxiang, Y., Guozheng, F., Weijie, H., Ni, S., Ying, H.

medrxiv logopreprintMay 8 2025
Accurate estimation of cerebral amyloid-{beta} (A{beta}) burden is critical for early detection and risk stratification in Alzheimers disease (AD). While A{beta} positron emission tomography (PET) remains the gold standard, its high cost, invasive nature and limited accessibility hinder broad clinical application. Blood-based biomarkers offer a non-invasive and cost-effective alternative, but their standalone predictive accuracy remains limited due to biological heterogeneity and limited reflection of central nervous system pathology. Here, we present a high-precision, multimodal prediction machine learning model that integrates plasma biomarkers, brain structural magnetic resonance imaging (sMRI) features, diffusion tensor imaging (DTI)-derived structural connectomes, and genetic risk profiles. The model was trained on 150 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI) and externally validated on 111 participants from the SILCODE cohort. Multimodal integration substantially improved A{beta} prediction, with R{superscript 2} increasing from 0.515 using plasma biomarkers alone to 0.637 when adding imaging and genetic features. These results highlight the potential of this multimodal machine learning approach as a scalable, non-invasive, and economically viable alternative to PET for estimating A{beta} burden.

FF-PNet: A Pyramid Network Based on Feature and Field for Brain Image Registration

Ying Zhang, Shuai Guo, Chenxi Sun, Yuchen Zhu, Jinhai Xiang

arxiv logopreprintMay 8 2025
In recent years, deformable medical image registration techniques have made significant progress. However, existing models still lack efficiency in parallel extraction of coarse and fine-grained features. To address this, we construct a new pyramid registration network based on feature and deformation field (FF-PNet). For coarse-grained feature extraction, we design a Residual Feature Fusion Module (RFFM), for fine-grained image deformation, we propose a Residual Deformation Field Fusion Module (RDFFM). Through the parallel operation of these two modules, the model can effectively handle complex image deformations. It is worth emphasizing that the encoding stage of FF-PNet only employs traditional convolutional neural networks without any attention mechanisms or multilayer perceptrons, yet it still achieves remarkable improvements in registration accuracy, fully demonstrating the superior feature decoding capabilities of RFFM and RDFFM. We conducted extensive experiments on the LPBA and OASIS datasets. The results show our network consistently outperforms popular methods in metrics like the Dice Similarity Coefficient.

Improved Brain Tumor Detection in MRI: Fuzzy Sigmoid Convolution in Deep Learning

Muhammad Irfan, Anum Nawaz, Riku Klen, Abdulhamit Subasi, Tomi Westerlund, Wei Chen

arxiv logopreprintMay 8 2025
Early detection and accurate diagnosis are essential to improving patient outcomes. The use of convolutional neural networks (CNNs) for tumor detection has shown promise, but existing models often suffer from overparameterization, which limits their performance gains. In this study, fuzzy sigmoid convolution (FSC) is introduced along with two additional modules: top-of-the-funnel and middle-of-the-funnel. The proposed methodology significantly reduces the number of trainable parameters without compromising classification accuracy. A novel convolutional operator is central to this approach, effectively dilating the receptive field while preserving input data integrity. This enables efficient feature map reduction and enhances the model's tumor detection capability. In the FSC-based model, fuzzy sigmoid activation functions are incorporated within convolutional layers to improve feature extraction and classification. The inclusion of fuzzy logic into the architecture improves its adaptability and robustness. Extensive experiments on three benchmark datasets demonstrate the superior performance and efficiency of the proposed model. The FSC-based architecture achieved classification accuracies of 99.17%, 99.75%, and 99.89% on three different datasets. The model employs 100 times fewer parameters than large-scale transfer learning architectures, highlighting its computational efficiency and suitability for detecting brain tumors early. This research offers lightweight, high-performance deep-learning models for medical imaging applications.

Impact of spectrum bias on deep learning-based stroke MRI analysis.

Krag CH, Müller FC, Gandrup KL, Plesner LL, Sagar MV, Andersen MB, Nielsen M, Kruuse C, Boesen M

pubmed logopapersMay 8 2025
To evaluate spectrum bias in stroke MRI analysis by excluding cases with uncertain acute ischemic lesions (AIL) and examining patient, imaging, and lesion factors associated with these cases. This single-center retrospective observational study included adults with brain MRIs for suspected stroke between January 2020 and April 2022. Diagnostic uncertain AIL were identified through reader disagreement or low certainty grading by a radiology resident, a neuroradiologist, and the original radiology report consisting of various neuroradiologists. A commercially available deep learning tool analyzing brain MRIs for AIL was evaluated to assess the impact of excluding uncertain cases on diagnostic odds ratios. Patient-related, MRI acquisition-related, and lesion-related factors were analyzed using the Wilcoxon rank sum test, χ2 test, and multiple logistic regression. The study was approved by the National Committee on Health Research Ethics. In 989 patients (median age 73 (IQR: 59-80), 53% female), certain AIL were found in 374 (38%), uncertain AIL in 63 (6%), and no AIL in 552 (56%). Excluding uncertain cases led to a four-fold increase in the diagnostic odds ratio (from 68 to 278), while a simulated case-control design resulted in a six-fold increase compared to the full disease spectrum (from 68 to 431). Independent factors associated with uncertain AIL were MRI artifacts, smaller lesion size, older lesion age, and infratentorial location. Excluding uncertain cases leads to a four-fold overestimation of the diagnostic odds ratio. MRI artifacts, smaller lesion size, infratentorial location, and older lesion age are associated with uncertain AIL and should be accounted for in validation studies.

Predicting the efficacy of bevacizumab on peritumoral edema based on imaging features and machine learning.

Bai X, Feng M, Ma W, Wang S

pubmed logopapersMay 8 2025
This study proposes a novel approach to predict the efficacy of bevacizumab (BEV) in treating peritumoral edema in metastatic brain tumor patients by integrating advanced machine learning (ML) techniques with comprehensive imaging and clinical data. A retrospective analysis was performed on 300 patients who received BEV treatment from September 2013 to January 2024. The dataset incorporated 13 predictive features: 8 clinical variables and 5 radiological variables. The dataset was divided into a training set (70%) and a test set (30%) using stratified sampling. Data preprocessing was carried out through methods such as handling missing values with the MICE method, detecting and adjusting outliers, and feature scaling. Four algorithms, namely Random Forest (RF), Logistic Regression, Gradient Boosting Tree, and Naive Bayes, were selected to construct binary classification models. A tenfold cross-validation strategy was implemented during training, and techniques like regularization, hyperparameter optimization, and oversampling were used to mitigate overfitting. The RF model demonstrated superior performance, achieving an accuracy of 0.89, a precision of 0.94, F1-score of 0.92, with both AUC-ROC and AUC-PR values reaching 0.91. Feature importance analysis consistently identified edema volume as the most significant predictor, followed by edema index, patient age, and tumor volume. Traditional multivariate logistic regression corroborated these findings, confirming that edema volume and edema index were independent predictors (p < 0.01). Our results highlight the potential of ML-driven predictive models in optimizing BEV treatment selection, reducing unnecessary treatment risks, and improving clinical decision-making in neuro-oncology.

Relevance of choroid plexus volumes in multiple sclerosis.

Krieger B, Bellenberg B, Roenneke AK, Schneider R, Ladopoulos T, Abbas Z, Rust R, Schmitz-Hübsch T, Chien C, Gold R, Paul F, Lukas C

pubmed logopapersMay 8 2025
The choroid plexus (ChP) plays a pivotal role in inflammatory processes that occur in multiple sclerosis (MS). The enlargement of the ChP in relapsing-remitting multiple sclerosis (RRMS) is considered to be an indication of disease activity and has been associated with periventricular remyelination failure. This cross-sectional study aimed to identify the relationship between ChP and periventricular tissue damage which occurs in MS, and to elucidate the role of neuroinflammation in primary progressive multiple sclerosis (PPMS). ChP volume was assessed by a novel deep learning segmentation method based on structural MRI data acquired from two centers. In total, 141 RRMS and 64 PPMS patients were included, along with 75 healthy control subjects. In addition, T1w/FLAIR ratios were calculated within periventricular bands to quantify microstructural tissue damage and to assess its relationship to ChP volume. When compared to healthy controls, ChP volumes were significantly increased in RRMS, but not in patients with PPMS. T1w/FLAIR ratios in the normal appearing white matter (NAWM) showing periventricular gradients were decreased in patients with multiple sclerosis when compared to healthy control subjects and lower T1w/FLAIR ratios radiating out from the lateral ventricles were found in patients with PPMS. A relationship between ChP volume and T1w/FLAIR ratio in NAWM was found within the inner periventricular bands in RRMS patients. A longer duration of disease was associated with larger ChP volumes only in RRMS patients. Enlarged ChP volumes were also significantly associated with reduced cortex volumes and increased lesion volumes in RRMS. Our analysis confirmed that the ChP was significantly enlarged in patients with RRMS, which was related to brain lesion volumes and which suggested a dynamic development as it was associated with disease duration. Plexus enlargement was further associated with periventricular demyelination or tissue damage assessed by T1w/FLAIR ratios in RRMS. Furthermore, we did not find an enlargement of the ChP in patients with PPMS, possibly indicating the reduced involvement of inflammatory processes in the progressive phase of MS. The association between enlarged ChP volumes and cortical atrophy in RRMS highlighted the vulnerability of structures close to the CSF.

Systematic review and epistemic meta-analysis to advance binomial AI-radiomics integration for predicting high-grade glioma progression and enhancing patient management.

Chilaca-Rosas MF, Contreras-Aguilar MT, Pallach-Loose F, Altamirano-Bustamante NF, Salazar-Calderon DR, Revilla-Monsalve C, Heredia-Gutiérrez JC, Conde-Castro B, Medrano-Guzmán R, Altamirano-Bustamante MM

pubmed logopapersMay 8 2025
High-grade gliomas, particularly glioblastoma (MeSH:Glioblastoma), are among the most aggressive and lethal central nervous system tumors, necessitating advanced diagnostic and prognostic strategies. This systematic review and epistemic meta-analysis explore the integration of Artificial Intelligence (AI) and Radiomics Inter-field (AIRI) to enhance predictive modeling for tumor progression. A comprehensive literature search identified 19 high-quality studies, which were analyzed to evaluate radiomic features and machine learning models in predicting overall survival (OS) and progression-free survival (PFS). Key findings highlight the predictive strength of specific MRI-derived radiomic features such as log-filter and Gabor textures and the superior performance of Support Vector Machines (SVM) and Random Forest (RF) models, achieving high accuracy and AUC scores (e.g., 98% AUC and 98.7% accuracy for OS). This research demonstrates the current state of the AIRI field and shows that current articles report their results with different performance indicators and metrics, making outcomes heterogenous and hard to integrate knowledge. Additionally, it was explored that today some articles use biased methodologies. This study proposes a structured AIRI development roadmap and guidelines, to avoid bias and make results comparable, emphasizing standardized feature extraction and AI model training to improve reproducibility across clinical settings. By advancing precision medicine, AIRI integration has the potential to refine clinical decision-making and enhance patient outcomes.

MRI-based machine learning reveals proteasome subunit PSMB8-mediated malignant glioma phenotypes through activating TGFBR1/2-SMAD2/3 axis.

Pei D, Ma Z, Qiu Y, Wang M, Wang Z, Liu X, Zhang L, Zhang Z, Li R, Yan D

pubmed logopapersMay 8 2025
Gliomas are the most prevalent and aggressive neoplasms of the central nervous system, representing a major challenge for effective treatment and patient prognosis. This study identifies the proteasome subunit beta type-8 (PSMB8/LMP7) as a promising prognostic biomarker for glioma. Using a multiparametric radiomic model derived from preoperative magnetic resonance imaging (MRI), we accurately predicted PSMB8 expression levels. Notably, radiomic prediction of poor prognosis was highly consistent with elevated PSMB8 expression. Our findings demonstrate that PSMB8 depletion not only suppressed glioma cell proliferation and migration but also induced apoptosis via activation of the transforming growth factor beta (TGF-β) signaling pathway. This was supported by downregulation of key receptors (TGFBR1 and TGFBR2). Furthermore, interference with PSMB8 expression impaired phosphorylation and nuclear translocation of SMAD2/3, critical mediators of TGF-β signaling. Consequently, these molecular alterations resulted in reduced tumor progression and enhanced sensitivity to temozolomide (TMZ), a standard chemotherapeutic agent. Overall, our findings highlight PSMB8's pivotal role in glioma pathophysiology and its potential as a prognostic marker. This study also demonstrates the clinical utility of MRI radiomics for preoperative risk stratification and pre-diagnosis. Targeted inhibition of PSMB8 may represent a therapeutic strategy to overcome TMZ resistance and improve glioma patient outcomes.

Are Diffusion Models Effective Good Feature Extractors for MRI Discriminative Tasks?

Li B, Sun Z, Li C, Kamagata K, Andica C, Uchida W, Takabayashi K, Guo S, Zou R, Aoki S, Tanaka T, Zhao Q

pubmed logopapersMay 8 2025
Diffusion models (DMs) excel in pixel-level and spatial tasks and are proven feature extractors for 2D image discriminative tasks when pretrained. However, their capabilities in 3D MRI discriminative tasks remain largely untapped. This study seeks to assess the effectiveness of DMs in this underexplored area. We use 59830 T1-weighted MR images (T1WIs) from the extensive, yet unlabeled, UK Biobank dataset. Additionally, we apply 369 T1WIs from the BraTS2020 dataset specifically for brain tumor classification, and 421 T1WIs from the ADNI1 dataset for the diagnosis of Alzheimer's disease. Firstly, a high-performing denoising diffusion probabilistic model (DDPM) with a U-Net backbone is pretrained on the UK Biobank, then fine-tuned on the BraTS2020 and ADNI1 datasets. Afterward, we assess its feature representation capabilities for discriminative tasks using linear probes. Finally, we accordingly introduce a novel fusion module, named CATS, that enhances the U-Net representations, thereby improving performance on discriminative tasks. Our DDPM produces synthetic images of high quality that match the distribution of the raw datasets. Subsequent analysis reveals that DDPM features extracted from middle blocks and smaller timesteps are of high quality. Leveraging these features, the CATS module, with just 1.7M additional parameters, achieved average classification scores of 0.7704 and 0.9217 on the BraTS2020 and ADNI1 datasets, demonstrating competitive performance with that of the representations extracted from the transferred DDPM model, as well as the 33.23M parameters ResNet18 trained from scratch. We have found that pretraining a DM on a large-scale dataset and then fine-tuning it on limited data from discriminative datasets is a viable approach for MRI data. With these well-performing DMs, we show that they excel not just in generation tasks but also as feature extractors when combined with our proposed CATS module.

Robust Computation of Subcortical Functional Connectivity Guided by Quantitative Susceptibility Mapping: An Application in Parkinson's Disease Diagnosis.

Qin J, Wu H, Wu C, Guo T, Zhou C, Duanmu X, Tan S, Wen J, Zheng Q, Yuan W, Zhu Z, Chen J, Wu J, He C, Ma Y, Liu C, Xu X, Guan X, Zhang M

pubmed logopapersMay 8 2025
Previous resting state functional MRI (rs-fMRI) analyses of the basal ganglia in Parkinson's disease heavily relied on T1-weighted imaging (T1WI) atlases. However, subcortical structures are characterized by subtle contrast differences, making their accurate delineation challenging on T1WI. In this study, we aimed to introduce and validate a method that incorporates quantitative susceptibility mapping (QSM) into the rs-fMRI analytical pipeline to achieve precise subcortical nuclei segmentation and improve the stability of RSFC measurements in Parkinson's disease. A total of 321 participants (148 patients with Parkinson's Disease and 173 normal controls) were enrolled. We performed cross-modal registration at the individual level for rs-fMRI to QSM (FUNC2QSM) and T1WI (FUNC2T1), respectively.The consistency and accuracy of resting state functional connectivity (RSFC) measurements in two registration approaches were assessed by intraclass correlation coefficient and mutual information. Bootstrap analysis was performed to validate the stability of the RSFC differences between Parkinson's disease and normal controls. RSFC-based machine learning models were constructed for Parkinson's disease classification, using optimized hyperparameters (RandomizedSearchCV with 5-fold cross-validation). The consistency of RSFC measurements between the two registration methods was poor, whereas the QSM-guided approach showed better mutual information values, suggesting higher registration accuracy. The disruptions of RSFC identified with the QSM-guided approach were more stable and reliable, as confirmed by bootstrap analysis. In classification models, the QSM-guided method consistently outperformed the T1WI-guided method, achieving higher test-set ROC-AUC values (FUNC2QSM: 0.87-0.90, FUNC2T1: 0.67-0.70). The QSM-guided approach effectively enhanced the accuracy of subcortical segmentation and the stability of RSFC measurement, thus facilitating future biomarker development in Parkinson's disease.
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