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Development and Validation of a Brain Aging Biomarker in Middle-Aged and Older Adults: Deep Learning Approach.

Li Z, Li J, Li J, Wang M, Xu A, Huang Y, Yu Q, Zhang L, Li Y, Li Z, Wu X, Bu J, Li W

pubmed logopapersAug 1 2025
Precise assessment of brain aging is crucial for early detection of neurodegenerative disorders and aiding clinical practice. Existing magnetic resonance imaging (MRI)-based methods excel in this task, but they still have room for improvement in capturing local morphological variations across brain regions and preserving the inherent neurobiological topological structures. To develop and validate a deep learning framework incorporating both connectivity and complexity for accurate brain aging estimation, facilitating early identification of neurodegenerative diseases. We used 5889 T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative dataset. We proposed a novel brain vision graph neural network (BVGN), incorporating neurobiologically informed feature extraction modules and global association mechanisms to provide a sensitive deep learning-based imaging biomarker. Model performance was evaluated using mean absolute error (MAE) against benchmark models, while generalization capability was further validated on an external UK Biobank dataset. We calculated the brain age gap across distinct cognitive states and conducted multiple logistic regressions to compare its discriminative capacity against conventional cognitive-related variables in distinguishing cognitively normal (CN) and mild cognitive impairment (MCI) states. Longitudinal track, Cox regression, and Kaplan-Meier plots were used to investigate the longitudinal performance of the brain age gap. The BVGN model achieved an MAE of 2.39 years, surpassing current state-of-the-art approaches while obtaining an interpretable saliency map and graph theory supported by medical evidence. Furthermore, its performance was validated on the UK Biobank cohort (N=34,352) with an MAE of 2.49 years. The brain age gap derived from BVGN exhibited significant difference across cognitive states (CN vs MCI vs Alzheimer disease; P<.001), and demonstrated the highest discriminative capacity between CN and MCI than general cognitive assessments, brain volume features, and apolipoprotein E4 carriage (area under the receiver operating characteristic curve [AUC] of 0.885 vs AUC ranging from 0.646 to 0.815). Brain age gap exhibited clinical feasibility combined with Functional Activities Questionnaire, with improved discriminative capacity in models achieving lower MAEs (AUC of 0.945 vs 0.923 and 0.911; AUC of 0.935 vs 0.900 and 0.881). An increasing brain age gap identified by BVGN may indicate underlying pathological changes in the CN to MCI progression, with each unit increase linked to a 55% (hazard ratio=1.55, 95% CI 1.13-2.13; P=.006) higher risk of cognitive decline in individuals who are CN and a 29% (hazard ratio=1.29, 95% CI 1.09-1.51; P=.002) increase in individuals with MCI. BVGN offers a precise framework for brain aging assessment, demonstrates strong generalization on an external large-scale dataset, and proposes novel interpretability strategies to elucidate multiregional cooperative aging patterns. The brain age gap derived from BVGN is validated as a sensitive biomarker for early identification of MCI and predicting cognitive decline, offering substantial potential for clinical applications.

Acute lymphoblastic leukemia diagnosis using machine learning techniques based on selected features.

El Houby EMF

pubmed logopapersAug 1 2025
Cancer is considered one of the deadliest diseases worldwide. Early detection of cancer can significantly improve patient survival rates. In recent years, computer-aided diagnosis (CAD) systems have been increasingly employed in cancer diagnosis through various medical image modalities. These systems play a critical role in enhancing diagnostic accuracy, reducing physician workload, providing consistent second opinions, and contributing to the efficiency of the medical industry. Acute lymphoblastic leukemia (ALL) is a fast-progressing blood cancer that primarily affects children but can also occur in adults. Early and accurate diagnosis of ALL is crucial for effective treatment and improved outcomes, making it a vital area for CAD system development. In this research, a CAD system for ALL diagnosis has been developed. It contains four phases which are preprocessing, segmentation, feature extraction and selection phase, and classification of suspicious regions as normal or abnormal. The proposed system was applied to microscopic blood images to classify each case as ALL or normal. Three classifiers which are Naïve Bayes (NB), Support Vector Machine (SVM) and K-nearest Neighbor (K-NN) were utilized to classify the images based on selected features. Ant Colony Optimization (ACO) was combined with the classifiers as a feature selection method to identify the optimal subset of features among the extracted features from segmented cell parts that yield the highest classification accuracy. The NB classifier achieved the best performance, with accuracy, sensitivity, and specificity of 96.15%, 97.56, and 94.59%, respectively.

Multimodal multiphasic preoperative image-based deep-learning predicts HCC outcomes after curative surgery.

Hui RW, Chiu KW, Lee IC, Wang C, Cheng HM, Lu J, Mao X, Yu S, Lam LK, Mak LY, Cheung TT, Chia NH, Cheung CC, Kan WK, Wong TC, Chan AC, Huang YH, Yuen MF, Yu PL, Seto WK

pubmed logopapersAug 1 2025
HCC recurrence frequently occurs after curative surgery. Histological microvascular invasion (MVI) predicts recurrence but cannot provide preoperative prognostication, whereas clinical prediction scores have variable performances. Recurr-NET, a multimodal multiphasic residual-network random survival forest deep-learning model incorporating preoperative CT and clinical parameters, was developed to predict HCC recurrence. Preoperative triphasic CT scans were retrieved from patients with resected histology-confirmed HCC from 4 centers in Hong Kong (internal cohort). The internal cohort was randomly divided in an 8:2 ratio into training and internal validation. External testing was performed in an independent cohort from Taiwan.Among 1231 patients (age 62.4y, 83.1% male, 86.8% viral hepatitis, and median follow-up 65.1mo), cumulative HCC recurrence rates at years 2 and 5 were 41.8% and 56.4%, respectively. Recurr-NET achieved excellent accuracy in predicting recurrence from years 1 to 5 (internal cohort AUROC 0.770-0.857; external AUROC 0.758-0.798), significantly outperforming MVI (internal AUROC 0.518-0.590; external AUROC 0.557-0.615) and multiple clinical risk scores (ERASL-PRE, ERASL-POST, DFT, and Shim scores) (internal AUROC 0.523-0.587, external AUROC: 0.524-0.620), respectively (all p < 0.001). Recurr-NET was superior to MVI in stratifying recurrence risks at year 2 (internal: 72.5% vs. 50.0% in MVI; external: 65.3% vs. 46.6% in MVI) and year 5 (internal: 86.4% vs. 62.5% in MVI; external: 81.4% vs. 63.8% in MVI) (all p < 0.001). Recurr-NET was also superior to MVI in stratifying liver-related and all-cause mortality (all p < 0.001). The performance of Recurr-NET remained robust in subgroup analyses. Recurr-NET accurately predicted HCC recurrence, outperforming MVI and clinical prediction scores, highlighting its potential in preoperative prognostication.

Effect of spatial resolution on the diagnostic performance of machine-learning radiomics model in lung adenocarcinoma: comparisons between normal- and high-spatial-resolution imaging for predicting invasiveness.

Yanagawa M, Nagatani Y, Hata A, Sumikawa H, Moriya H, Iwano S, Tsuchiya N, Iwasawa T, Ohno Y, Tomiyama N

pubmed logopapersJul 31 2025
To construct two machine learning radiomics (MLR) for invasive adenocarcinoma (IVA) prediction using normal-spatial-resolution (NSR) and high-spatial-resolution (HSR) training cohorts, and to validate models (model-NSR and -HSR) in another test cohort while comparing independent radiologists' (R1, R2) performance with and without model-HSR. In this retrospective multicenter study, all CT images were reconstructed using NSR data (512 matrix, 0.5-mm thickness) and HSR data (2048 matrix, 0.25-mm thickness). Nodules were divided into training (n = 61 non-IVA, n = 165 IVA) and test sets (n = 36 non-IVA, n = 203 IVA). Two MLR models were developed with 18 significant factors for the NSR model and 19 significant factors for the HSR model from 172 radiomics features using random forest. Area under the receiver operator characteristic curves (AUC) was analyzed using DeLong's test in the test set. Accuracy (acc), sensitivity (sen), and specificity (spc) of R1 and R2 with and without model-HSR were compared using McNemar test. 437 patients (70 ± 9 years, 203 men) had 465 nodules (n = 368, IVA). Model-HSR AUCs were significantly higher than model-NSR in training (0.839 vs. 0.723) and test sets (0.863 vs. 0.718) (p < 0.05). R1's acc (87.2%) and sen (93.1%) with model-HSR were significantly higher than without (77.0% and 79.3%) (p < 0.0001). R2's acc (83.7%) and sen (86.7%) with model-HSR might be equal or higher than without (83.7% and 85.7%, respectively), but not significant (p > 0.50). Spc of R1 (52.8%) and R2 (66.7%) with model-HSR might be lower than without (63.9% and 72.2%, respectively), but not significant (p > 0.21). HSR-based MLR model significantly increased IVA diagnostic performance compared to NSR, supporting radiologists without compromising accuracy and sensitivity. However, this benefit came at the cost of reduced specificity, potentially increasing false positives, which may lead to unnecessary examinations or overtreatment in clinical settings.

Technological advancements in sports injury: diagnosis and treatment.

Zhong Z, DI W

pubmed logopapersJul 31 2025
Sports injuries are a significant concern for athletes at all levels of competition, ranging from acute traumas to chronic conditions. Prompt diagnosis and effective treatment are crucial for an athlete's recovery and quality of life. Traditionally, sports injury diagnosis has relied on clinical assessments, patient history, and basic imaging techniques such as X-rays, ultrasound, and magnetic resonance imaging (MRI). However, recent technological advancements have revolutionized the field of sports medicine, offering more accurate diagnoses and targeted treatment strategies. High-resolution MRI and CT scans provide detailed images of deep tissue injuries, while advanced ultrasound technology enables on-field diagnostics. Wearable sensor devices and machine learning algorithms allow real-time monitoring of an athlete's movements and physical loads, facilitating early intervention and injury risk prediction. Regenerative medicine, including stem cell therapy and tissue engineering, has emerged as a transformative approach to healing damaged tissues and reducing treatment time. Despite the challenges of high costs, lack of skilled personnel, and ethical considerations, the integration of artificial intelligence and machine learning into sports medicine holds immense potential for revolutionizing injury prevention and management. As these advancements continue to evolve, they are expected to extend athletes' careers and enhance their overall quality of life. This review summarizes conventional methods to diagnose and manage injuries and provides insights into the recent advancements in the field of sports science and medicine. It also states future outlook on the diagnosis and treatment of sports injuries.

Identification and validation of an explainable machine learning model for vascular depression diagnosis in the older adults: a multicenter cohort study.

Zhang R, Li T, Fan F, He H, Lan L, Sun D, Xu Z, Peng S, Cao J, Xu J, Peng X, Lei M, Song H, Zhang J

pubmed logopapersJul 31 2025
Vascular depression (VaDep) is a prevalent affective disorder in older adults that significantly impacts functional status and quality of life. Early identification and intervention are crucial but largely insufficient in clinical practice due to inconspicuous depressive symptoms mostly, heterogeneous imaging manifestations, and the lack of definitive peripheral biomarkers. This study aimed to develop and validate an interpretable machine learning (ML) model for VaDep to serve as a clinical support tool. This study included 602 participants from Wuhan in China divided into 236 VaDep patients and 366 controls for training and internal validation from July 2020 to October 2023. An independent dataset of 171 participants from surrounding areas was used for external validation. We collected clinical data, neuropsychological assessments, blood test results, and MRI scans to develop and refine ML models through cross-validation. Feature reduction was implemented to simplify the models without compromising their performance, with validation achieved through internal and external datasets. The SHapley Additive exPlanations method was used to enhance model interpretability. The Light Gradient Boosting Machine (LGBM) model outperformed from the selected 6 ML algorithms based on performance metrics. An optimized, interpretable LGBM model with 8 key features, including white matter hyperintensities score, age, vascular endothelial growth factor, interleukin-6, brain-derived neurotrophic factor, tumor necrosis factor-alpha levels, lacune counts, and serotonin level, demonstrated high diagnostic accuracy in both internal (AUROC = 0.937) and external (AUROC = 0.896) validations. The final model also achieved, and marginally exceeded, clinician-level diagnostic performance. Our research established a consistent and explainable ML framework for identifying VaDep in older adults, utilizing comprehensive clinical data. The 8 characteristics identified in the final LGBM model provide new insights for further exploration of VaDep mechanisms and emphasize the need for enhanced focus on early identification and intervention in this vulnerable group. More attention needs to be paid to the affective health of older adults.

Cognitive profiles associated with faster thalamic atrophy in multiple sclerosis.

Amin M, Scullin K, Nakamura K, Ontaneda D, Galioto R

pubmed logopapersJul 31 2025
Cognitive impairment (CI) in people with MS (pwMS) has complex pathophysiology. Neuropsychological testing (NPT) can be helpful, but interpretation may be challenging for clinicians. Thalamic atrophy (TA) has shown correlation for both neurodegeneration and CI. Leverage machine learning methods to link CI and longitudinal neuroimaging biomarkers. Retrospective review of adult pwMS with NPT and ≥2 brain MRIs. Quantitative MRI regional change rates were calculated using mixed effects models. Participants were divided into training and validation cohorts. K-means clustering was done based on first and second NPT principal components (PC1 and PC2). MRI change rates were compared between clusters. 112 participants were included (mean age 48 years, 71 % female, 80 % relapsing remitting). Processing speed and memory were the major contributors to PC1. We identified two clusters based on PC1, one with significantly more TA in both training and validation cohorts (p = 0.035; p = 0.002) and similar rates of change in all other quantitative MRI measures. The most important contributors to PC1 included measures of processing speed (SDMT/WAIS Coding) and memory (List Learning/BVMT immediate and delayed recall). This clustering method identified a profile of NPT results strongly linked to and possibly driven by TA. These results confirm validity of previously established findings using more advanced analyses in addition to offering novel insights into NPT dimensionality reduction.

Application of Tuning-Ensemble N-Best in Auto-Sklearn for Mammographic Radiomic Analysis for Breast Cancer Prediction.

Ismail FA, Karim MKA, Zaidon SIA, Noor KA

pubmed logopapersJul 31 2025
Breast cancer is a major cause of mortality among women globally. While mammography remains the gold standard for detection, its interpretation is often limited by radiologist variability and the challenge of differentiating benign and malignant lesions. The study explores the use of Auto- Sklearn, an automated machine learning (AutoML) framework, for breast tumor classification based on mammographic radiomic features. 244 mammographic images were enhanced using Contrast Limited Adaptive Histogram Equalization (CLAHE) and segmented with Active Contour Method (ACM). Thirty-seven radiomic features, including first-order statistics, Gray-Level Co-occurance Matrix (GLCM) texture and shape features were extracted and standardized. Auto-Sklearn was employed to automate model selection, hyperparameter tuning and ensemble construction. The dataset was divided into 80% training and 20% testing set. The initial Auto-Sklearn model achieved an 88.71% accuracy on the training set and 55.10% on the testing sets. After the resampling strategy was applied, the accuracy for the training set and testing set increased to 95.26% and 76.16%, respectively. The Receiver Operating Curve and Area Under Curve (ROC-AUC) for the standard and resampling strategy of Auto-Sklearn were 0.660 and 0.840, outperforming conventional models, demonstrating its efficiency in automating radiomic classification tasks. The findings underscore Auto-Sklearn's ability to automate and enhance tumor classification performance using handcrafted radiomic features. Limitations include dataset size and absence of clinical metadata. This study highlights the application of Auto-Sklearn as a scalable, automated and clinically relevant tool for breast cancer classification using mammographic radiomics.

Effectiveness of Radiomics-Based Machine Learning Models in Differentiating Pancreatitis and Pancreatic Ductal Adenocarcinoma: Systematic Review and Meta-Analysis.

Zhang L, Li D, Su T, Xiao T, Zhao S

pubmed logopapersJul 31 2025
Pancreatic ductal adenocarcinoma (PDAC) and mass-forming pancreatitis (MFP) share similar clinical, laboratory, and imaging features, making accurate diagnosis challenging. Nevertheless, PDAC is highly malignant with a poor prognosis, whereas MFP is an inflammatory condition typically responding well to medical or interventional therapies. Some investigators have explored radiomics-based machine learning (ML) models for distinguishing PDAC from MFP. However, systematic evidence supporting the feasibility of these models is insufficient, presenting a notable challenge for clinical application. This study intended to review the diagnostic performance of radiomics-based ML models in differentiating PDAC from MFP, summarize the methodological quality of the included studies, and provide evidence-based guidance for optimizing radiomics-based ML models and advancing their clinical use. PubMed, Embase, Cochrane, and Web of Science were searched for relevant studies up to June 29, 2024. Eligible studies comprised English cohort, case-control, or cross-sectional designs that applied fully developed radiomics-based ML models-including traditional and deep radiomics-to differentiate PDAC from MFP, while also reporting their diagnostic performance. Studies without full text, limited to image segmentation, or insufficient outcome metrics were excluded. Methodological quality was appraised by means of the radiomics quality score. Since the limited applicability of QUADAS-2 in radiomics-based ML studies, the risk of bias was not formally assessed. Pooled sensitivity, specificity, area under the curve of summary receiver operating characteristics (SROC), likelihood ratios, and diagnostic odds ratio were estimated through a bivariate mixed-effects model. Results were presented with forest plots, SROC curves, and Fagan's nomogram. Subgroup analysis was performed to appraise the diagnostic performance of radiomics-based ML models across various imaging modalities, including computed tomography (CT), magnetic resonance imaging, positron emission tomography-CT, and endoscopic ultrasound. This meta-analysis included 24 studies with 14,406 cases, including 7635 PDAC cases. All studies adopted a case-control design, with 5 conducted across multiple centers. Most studies used CT as the primary imaging modality. The radiomics quality score scores ranged from 5 points (14%) to 17 points (47%), with an average score of 9 (25%). The radiomics-based ML models demonstrated high diagnostic performance. Based on the independent validation sets, the pooled sensitivity, specificity, area under the curve of SROC, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.92 (95% CI 0.91-0.94), 0.90 (95% CI 0.85-0.94), 0.94 (95% CI 0.74-0.99), 9.3 (95% CI 6.0-14.2), 0.08 (95% CI 0.07-0.11), and 110 (95% CI 62-194), respectively. Radiomics-based ML models demonstrate high diagnostic accuracy in differentiating PDAC from MFP, underscoring their potential as noninvasive tools for clinical decision-making. Nonetheless, the overall methodological quality was moderate due to limitations in external validation, standardized protocols, and reproducibility. These findings support the promise of radiomics in clinical diagnostics while highlighting the need for more rigorous, multicenter research to enhance model generalizability and clinical applicability.

Precision Medicine in Substance Use Disorders: Integrating Behavioral, Environmental, and Biological Insights.

Guerrin CGJ, Tesselaar DRM, Booij J, Schellekens AFA, Homberg JR

pubmed logopapersJul 31 2025
Substance use disorders (SUD) are chronic, relapsing conditions marked by high variability in treatment response and frequent relapse. This variability arises from complex interactions among behavioral, environmental, and biological factors unique to each individual. Precision medicine, which tailors treatment to patient-specific characteristics, offers a promising avenue to address these challenges. This review explores key factors influencing SUD, including severity, comorbidities, drug use motives, polysubstance use, cognitive impairments, and biological and environmental influences. Advanced neuroimaging, such as MRI and PET, enables patient subtyping by identifying altered brain mechanisms, including reward, relief, and cognitive pathways, and striatal dopamine D<sub>2/3</sub> receptor binding. Pharmacogenetic and epigenetic studies uncover how variations in dopaminergic, serotoninergic, and opioidergic systems shape treatment outcomes. Emerging biomarkers, such as neurofilament light chain, offer non-invasive relapse monitoring. Multifactorial models integrating behavioral and neural markers outperform single-factor approaches in predicting treatment success. Machine learning refines these models, while longitudinal and preclinical studies support individualized care. Despite translational hurdles, precision medicine offers transformative potential for improving SUD treatment outcomes.
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