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Decision Strategies in AI-Based Ensemble Models in Opportunistic Alzheimer's Detection from Structural MRI.

Hammonds SK, Eftestøl T, Kurz KD, Fernandez-Quilez A

pubmed logopapersSep 17 2025
Alzheimer's disease (AD) is a neurodegenerative condition and the most common form of dementia. Recent developments in AD treatment call for robust diagnostic tools to facilitate medical decision-making. Despite progress for early diagnostic tests, there remains uncertainty about clinical use. Structural magnetic resonance imaging (MRI), as a readily available imaging tool in the current AD diagnostic pathway, in combination with artificial intelligence, offers opportunities of added value beyond symptomatic evaluation. However, MRI studies in AD tend to suffer from small datasets and consequently limited generalizability. Although ensemble models take advantage of the strengths of several models to improve performance and generalizability, there is little knowledge of how the different ensemble models compare performance-wise and the relationship between detection performance and model calibration. The latter is especially relevant for clinical translatability. In our study, we applied three ensemble decision strategies with three different deep learning architectures for multi-class AD detection with structural MRI. For two of the three architectures, the weighted average was the best decision strategy in terms of balanced accuracy and calibration error. In contrast to the base models, the results of the ensemble models showed that the best detection performance corresponded to the lowest calibration error, independent of the architecture. For each architecture, the best ensemble model reduced the estimated calibration error compared to the base model average from (1) 0.174±0.01 to 0.164±0.04, (2) 0.182±0.02 to 0.141±0.04, and (3) 0.269±0.08 to 0.240±0.04 and increased the balanced accuracy from (1) 0.527±0.05 to 0.608±0.06, (2) 0.417±0.03 to 0.456±0.04, and (3) 0.348±0.02 to 0.371±0.03.

Automating classification of treatment responses to combined targeted therapy and immunotherapy in HCC.

Quan B, Dai M, Zhang P, Chen S, Cai J, Shao Y, Xu P, Li P, Yu L

pubmed logopapersSep 17 2025
Tyrosine kinase inhibitors (TKIs) combined with immunotherapy regimens are now widely used for treating advanced hepatocellular carcinoma (HCC), but their clinical efficacy is limited to a subset of patients. Considering that the vast majority of advanced HCC patients lose the opportunity for liver resection and thus cannot provide tumor tissue samples, we leveraged the clinical and image data to construct a multimodal convolutional neural network (CNN)-Transformer model for predicting and analyzing tumor response to TKI-immunotherapy. An automatic liver tumor segmentation system, based on a two-stage 3D U-Net framework, delineates lesions by first segmenting the liver parenchyma and then precisely localizing the tumor. This approach effectively addresses the variability in clinical data and significantly reduces bias introduced by manual intervention. Thus, we developed a clinical model using only pre-treatment clinical information, a CNN model using only pre-treatment magnetic resonance imaging data, and an advanced multimodal CNN-Transformer model that fused imaging and clinical parameters using a training cohort (n = 181) and then validated them using an independent cohort (n = 30). In the validation cohort, the area under the curve (95% confidence interval) values were 0.720 (0.710-0.731), 0.695 (0.683-0.707), and 0.785 (0.760-0.810), respectively, indicating that the multimodal model significantly outperformed the single-modality baseline models across validations. Finally, single-cell sequencing with the surgical tumor specimens reveals tumor ecosystem diversity associated with treatment response, providing a preliminary biological validation for the prediction model. In summary, this multimodal model effectively integrates imaging and clinical features of HCC patients, has a superior performance in predicting tumor response to TKI-immunotherapy, and provides a reliable tool for optimizing personalized treatment strategies.

Non-iterative and uncertainty-aware MRI-based liver fat estimation using an unsupervised deep learning method.

Meneses JP, Tejos C, Makalic E, Uribe S

pubmed logopapersSep 17 2025
Liver proton density fat fraction (PDFF), the ratio between fat-only and overall proton densities, is an extensively validated biomarker associated with several diseases. In recent years, numerous deep learning-based methods for estimating PDFF have been proposed to optimize acquisition and post-processing times without sacrificing accuracy, compared to conventional methods. However, the lack of interpretability and the often poor generalizability of these DL-based models undermine the adoption of such techniques in clinical practice. In this work, we propose an Artificial Intelligence-based Decomposition of water and fat with Echo Asymmetry and Least-squares (AI-DEAL) method, designed to estimate both proton density fat fraction (PDFF) and the associated uncertainty maps. Once trained, AI-DEAL performs a one-shot MRI water-fat separation by first calculating the nonlinear confounder variables, R<sub>2</sub><sup>∗</sup> and off-resonance field. It then employs a weighted least squares approach to compute water-only and fat-only signals, along with their corresponding covariance matrix, which are subsequently used to derive the PDFF and its associated uncertainty. We validated our method using in vivo liver CSE-MRI, a fat-water phantom, and a numerical phantom. AI-DEAL demonstrated PDFF biases of 0.25% and -0.12% at two liver ROIs, outperforming state-of-the-art deep learning-based techniques. Although trained using in vivo data, our method exhibited PDFF biases of -3.43% in the fat-water phantom and -0.22% in the numerical phantom with no added noise. The latter bias remained approximately constant when noise was introduced. Furthermore, the estimated uncertainties showed good agreement with the observed errors and the variations within each ROI, highlighting their potential value for assessing the reliability of the resulting PDFF maps.

Machine and deep learning for MRI-based quantification of liver iron overload: a systematic review and meta-analysis.

Elhaie M, Koozari A, Alshammari QT

pubmed logopapersSep 16 2025
Liver iron overload, associated with conditions such as hereditary hemochromatosis and β‑thalassemia major, requires accurate quantification of liver iron concentration (LIC) to guide timely interventions and prevent complications. Magnetic resonance imaging (MRI) is the gold standard for noninvasive LIC assessment, but challenges in protocol variability and diagnostic consistency persist. Machine learning (ML) and deep learning (DL) offer potential to enhance MRI-based LIC quantification, yet their efficacy remains underexplored. This systematic review and meta-analysis evaluates the diagnostic accuracy, algorithmic performance, and clinical applicability of ML and DL techniques for MRI-based LIC quantification in liver iron overload, adhering to PRISMA guidelines. A comprehensive search across PubMed, Embase, Scopus, Web of Science, Cochrane Library, and IEEE Xplore identified studies applying ML/DL to MRI-based LIC quantification. Eligible studies were assessed for diagnostic accuracy (sensitivity, specificity, AUC), LIC quantification precision (correlation, mean absolute error), and clinical applicability (automation, processing time). Methodological quality was evaluated using the QUADAS‑2 tool, with qualitative synthesis and meta-analysis where feasible. Eight studies were included, employing algorithms such as convolutional neural networks (CNNs), radiomics, and fuzzy C‑mean clustering on T2*-weighted and multiparametric MRI. Pooled diagnostic accuracy from three studies showed a sensitivity of 0.79 (95% CI: 0.66-0.88) and specificity of 0.77 (95% CI: 0.64-0.86), with an AUC of 0.84. The DL methods demonstrated high precision (e.g., Pearson's r = 0.999) and automation, reducing processing times to as low as 0.1 s/slice. Limitations included heterogeneity, limited generalizability, and small external validation sets. Both ML and DL enhance MRI-based LIC quantification, offering high accuracy and efficiency. Standardized protocols and multicenter validation are needed to ensure clinical scalability and equitable access.

Multi-Atlas Brain Network Classification through Consistency Distillation and Complementary Information Fusion.

Xu J, Lan M, Dong X, He K, Zhang W, Bian Q, Ke Y

pubmed logopapersSep 16 2025
Brain network analysis plays a crucial role in identifying distinctive patterns associated with neurological disorders. Functional magnetic resonance imaging (fMRI) enables the construction of brain networks by analyzing correlations in blood-oxygen-level-dependent (BOLD) signals across different brain regions, known as regions of interest (ROIs). These networks are typically constructed using atlases that parcellate the brain based on various hypotheses of functional and anatomical divisions. However, there is no standard atlas for brain network classification, leading to limitations in detecting abnormalities in disorders. Recent methods leveraging multiple atlases fail to ensure consistency across atlases and lack effective ROI-level information exchange, limiting their efficacy. To address these challenges, we propose the Atlas-Integrated Distillation and Fusion network (AIDFusion), a novel framework designed to enhance brain network classification using fMRI data. AIDFusion introduces a disentangle Transformer to filter out inconsistent atlas-specific information and distill meaningful cross-atlas connections. Additionally, it enforces subject- and population-level consistency constraints to improve cross-atlas coherence. To further enhance feature integration, AIDFusion incorporates an inter-atlas message-passing mechanism that facilitates the fusion of complementary information across brain regions. We evaluate AIDFusion on four resting-state fMRI datasets encompassing different neurological disorders. Experimental results demonstrate its superior classification performance and computational efficiency compared to state-of-the-art methods. Furthermore, a case study highlights AIDFusion's ability to extract interpretable patterns that align with established neuroscience findings, reinforcing its potential as a robust tool for multi-atlas brain network analysis. The code is publicly available at https://github.com/AngusMonroe/AIDFusion.

Automated Field of View Prescription for Whole-body Magnetic Resonance Imaging Using Deep Learning Based Body Region Segmentations.

Quinsten AS, Bojahr C, Nassenstein K, Straus J, Holtkamp M, Salhöfer L, Umutlu L, Forsting M, Haubold J, Wen Y, Kohnke J, Borys K, Nensa F, Hosch R

pubmed logopapersSep 16 2025
Manual field-of-view (FoV) prescription in whole-body magnetic resonance imaging (WB-MRI) is vital for ensuring comprehensive anatomic coverage and minimising artifacts, thereby enhancing image quality. However, this procedure is time-consuming, subject to operator variability, and adversely impacts both patient comfort and workflow efficiency. To overcome these limitations, an automated system was developed and evaluated that prescribes multiple consecutive FoV stations for WB-MRI using deep-learning (DL)-based three-dimensional anatomic segmentations. A total of 374 patients (mean age: 50.5 ± 18.2 y; 52% females) who underwent WB-MRI, including T2-weighted Half-Fourier acquisition single-shot turbo spin-echo (T2-HASTE) and fast whole-body localizer (FWBL) sequences acquired during continuous table movement on a 3T MRI system, were retrospectively collected between March 2012 and January 2025. An external cohort of 10 patients, acquired on two 1.5T scanners, was utilized for generalizability testing. Complementary nnUNet-v2 models were fine-tuned to segment tissue compartments, organs, and a whole-body (WB) outline on FWBL images. From these predicted segmentations, 5 consecutive FoVs (head/neck, thorax, liver, pelvis, and spine) were generated. Segmentation accuracy was quantified by Sørensen-Dice coefficients (DSC), Precision (P), Recall (R), and Specificity (S). Clinical utility was assessed on 30 test cases by 4 blinded experts using Likert scores and a 4-way ranking against 3 radiographer prescriptions. Interrater reliability and statistical comparisons were employed using the intraclass correlation coefficient (ICC), Kendall W, Friedman, and Wilcoxon signed-rank tests. Mean DSCs were 0.98 for torso (P = 0.98, R = 0.98, S = 1.00), 0.96 for head/neck (P = 0.95, R = 0.96, S = 1.00), 0.94 for abdominal cavity (P = 0.95, R = 0.94, S = 1.00), 0.90 for thoracic cavity (P = 0.90, R = 0.91, S = 1.00), 0.86 for liver (P = 0.85, R = 0.87, S = 1.00), and 0.63 for spinal cord (P = 0.64, R = 0.63, S = 1.00). The clinical utility was evidenced by assessments from 2 expert radiologists and 2 radiographers, with 98.3% and 87.5% of cases rated as clinically acceptable in the internal test data set and the external test data set. Predicted FoVs received the highest ranking in 60% of cases. They placed within the top 2 in 85.8% of cases, outperforming radiographers with 9 and 13 years of experience (P < 0.001) and matching the performance of a radiographer with 20 years of experience. DL-based three-dimensional anatomic segmentations enable accurate and reliable multistation FoV prescription for WB-MRI, achieving expert-level performance while significantly reducing manual workload. Automated FoV planning has the potential to standardize WB-MRI acquisition, reduce interoperator variability, and enhance workflow efficiency, thereby facilitating broader clinical adoption.

Concurrent AI assistance with LI-RADS classification for contrast enhanced MRI of focal hepatic nodules: a multi-reader, multi-case study.

Qin X, Huang L, Wei Y, Li H, Wu Y, Zhong J, Jian M, Zhang J, Zheng Z, Xu Y, Yan C

pubmed logopapersSep 16 2025
The Liver Imaging Reporting and Data System (LI-RADS) assessment is subject to inter-reader variability. The present study aimed to evaluate the impact of an artificial intelligence (AI) system on the accuracy and inter-reader agreement of LI-RADS classification based on contrast-enhanced magnetic resonance imaging among radiologists with varying experience levels. This single-center, multi-reader, multi-case retrospective study included 120 patients with 200 focal liver lesions who underwent abdominal contrast-enhanced magnetic resonance imaging examinations between June 2023 and May 2024. Five radiologists with different experience levels independently assessed LI-RADS classification and imaging features with and without AI assistance. The reference standard was established by consensus between two expert radiologists. Accuracy was used to measure the performance of AI systems and radiologists. Kappa or intraclass correlation coefficient was utilized to estimate inter-reader agreement. The LI-RADS categories were as follows: 33.5% of LR-3 (67/200), 29.0% of LR-4 (58/200), 33.5% of LR-5 (67/200), and 4.0% of LR-M (8/200) cases. The AI system significantly improved the overall accuracy of LI-RADS classification from 69.9 to 80.1% (p < 0.001), with the most notable improvement among junior radiologists from 65.7 to 79.7% (p < 0.001). Inter-reader agreement for LI-RADS classification was significantly higher with AI assistance compared to that without (weighted Cohen's kappa, 0.655 vs. 0.812, p < 0.001). The AI system also enhanced the accuracy and inter-reader agreement for imaging features, including non-rim arterial phase hyperenhancement, non-peripheral washout, and restricted diffusion. Additionally, inter-reader agreement for lesion size measurements improved, with intraclass correlation coefficient changing from 0.857 to 0.951 (p < 0.001). The AI system significantly increases accuracy and inter-reader agreement of LI-RADS 3/4/5/M classification, particularly benefiting junior radiologists.

The HeartMagic prospective observational study protocol - characterizing subtypes of heart failure with preserved ejection fraction

Meyer, P., Rocca, A., Banus, J., Ogier, A. C., Georgantas, C., Calarnou, P., Fatima, A., Vallee, J.-P., Deux, J.-F., Thomas, A., Marquis, J., Monney, P., Lu, H., Ledoux, J.-B., Tillier, C., Crowe, L. A., Abdurashidova, T., Richiardi, J., Hullin, R., van Heeswijk, R. B.

medrxiv logopreprintSep 16 2025
Introduction Heart failure (HF) is a life-threatening syndrome with significant morbidity and mortality. While evidence-based drug treatments have effectively reduced morbidity and mortality in HF with reduced ejection fraction (HFrEF), few therapies have been demonstrated to improve outcomes in HF with preserved ejection fraction (HFpEF). The multifaceted clinical presentation is one of the main reasons why the current understanding of HFpEF remains limited. This may be caused by the existence of several HFpEF disease subtypes that each need different treatments. There is therefore an unmet need for a holistic approach that combines comprehensive imaging with metabolomic, transcriptomic and genomic mapping to subtype HFpEF patients. This protocol details the approach employed in the HeartMagic study to address this gap in understanding. Methods This prospective multi-center observational cohort study will include 500 consecutive patients with actual or recent hospitalization for treatment of HFpEF at two Swiss university hospitals, along with 50 age-matched HFrEF patients and 50 age-matched healthy controls. Diagnosis of heart failure is based on clinical signs and symptoms and subgrouping HF patients is based on the left-ventricular ejection fraction. In addition to routine clinical workup, participants undergo genomic, transcriptomic, and metabolomic analyses, while the anatomy, composition, and function of the heart are quantified by comprehensive echocardiography and magnetic resonance imaging (MRI). Quantitative MRI is also applied to characterize the kidney. The primary outcome is a composite of one-year cardiovascular mortality or rehospitalization. Machine learning (ML) based multi-modal clustering will be employed to identify distinct HFpEF subtypes in the holistic data. The clinical importance of these subtypes shall be evaluated based on their association with the primary outcome. Statistical analysis will include group comparisons across modalities, survival analysis for the primary outcome, and integrative multi-modal clustering combining clinical, imaging, ECG, genomic, transcriptomic, and metabolomic data to identify and validate HFpEF subtypes. Discussion The integration of comprehensive MRI with extensive genomic and metabolomic profiling in this study will result in an unprecedented panoramic view of HFpEF and should enable us to distinguish functional subgroups of HFpEF patients. This approach has the potential to provide unprecedented insights on HFpEF disease and should provide a basis for personalized therapies. Beyond this, identifying HFpEF subtypes with specific molecular and structural characteristics could lead to new targeted pharmacological interventions, with the potential to improve patient outcomes.

Prediction of cerebrospinal fluid intervention in fetal ventriculomegaly via AI-powered normative modelling.

Zhou M, Rajan SA, Nedelec P, Bayona JB, Glenn O, Gupta N, Gano D, George E, Rauschecker AM

pubmed logopapersSep 16 2025
Fetal ventriculomegaly (VM) is common and largely benign when isolated. However, it can occasionally progress to hydrocephalus, a more severe condition associated with increased mortality and neurodevelopmental delay that may require surgical postnatal intervention. Accurate differentiation between VM and hydrocephalus is essential but remains challenging, relying on subjective assessment and limited two-dimensional measurements. Deep learning-based segmentation offers a promising solution for objective and reproducible volumetric analysis. This work presents an AI-powered method for segmentation, volume quantification, and classification of the ventricles in fetal brain MRI to predict need for postnatal intervention. This retrospective study included 222 patients with singleton pregnancies. An nnUNet was trained to segment the fetal ventricles on 20 manually segmented, institutional fetal brain MRIs combined with 80 studies from a publicly available dataset. The validated model was then applied to 138 normal fetal brain MRIs to generate a normative reference range across a range of gestational ages (18-36 weeks). Finally it was applied to 64 fetal brains with VM (14 of which required postnatal intervention). ROC curves and AUC to predict VM and need for postnatal intervention were calculated. The nnUNet predicted segmentation of the fetal ventricles in the reference dataset were high quality and accurate (median Dice score 0.96, IQR 0.93-0.99). A normative reference range of ventricular volumes across gestational ages was developed using automated segmentation volumes. The optimal threshold for identifying VM was 2 standard deviations from normal with sensitivity of 92% and specificity of 93% (AUC 0.97, 95% CI 0.91-0.98). When normalized to intracranial volume, fetal ventricular volume was higher and subarachnoid volume lower among those who required postnatal intervention (p<0.001, p=0.003). The optimal threshold for identifying need for postnatal intervention was 11 standard deviations from normal with sensitivity of 86% and specificity of 100% (AUC 0.97, 95% CI 0.86-1.00). This work introduces a deep-learning based method for fast and accurate quantification of ventricular volumes in fetal brain MRI. A normative reference standard derived using this method can predict VM and need for postnatal CSF intervention. Increased ventricular volume is a strong predictor for postnatal intervention. VM = ventriculomegaly, 2D = two-dimensional, 3D = three-dimensional, ROC = receiver operating characteristics, AUC = area under curve.

Automated brain extraction for canine magnetic resonance images.

Lesta GD, Deserno TM, Abani S, Janisch J, Hänsch A, Laue M, Winzer S, Dickinson PJ, De Decker S, Gutierrez-Quintana R, Subbotin A, Bocharova K, McLarty E, Lemke L, Wang-Leandro A, Spohn F, Volk HA, Nessler JN

pubmed logopapersSep 16 2025
Brain extraction is a common preprocessing step when working with intracranial medical imaging data. While several tools exist to automate the preprocessing of magnetic resonance imaging (MRI) of the human brain, none are available for canine MRIs. We present a pipeline mapping separate 2D scans to a 3D image, and a neural network for canine brain extraction. The training dataset consisted of T1-weighted and contrast-enhanced images from 68 dogs of different breeds, all cranial conformations (mesaticephalic, dolichocephalic, brachycephalic), with several pathological conditions, taken at three institutions. Testing was performed on a similarly diverse group of 10 dogs with images from a 4th institution. The model achieved excellent results in terms of Dice ([Formula: see text]) and Jaccard ([Formula: see text]) metrics and generalised well across different MRI scanners, the three aforementioned skull types, and variations in head size and breed. The pipeline was effective for a combination of one to three acquisition planes (i.e., transversal, dorsal, and sagittal). Aside from the T1 weighted imaging training datasets, the model also performed well on other MRI sequences with Jaccardian indices and median Dice scores ranging from 0.86 to 0.89 and 0.92 to 0.94, respectively. Our approach was robust for automated brain extraction. Variations in canine anatomy and performance degradation in multi-scanner data can largely be mitigated through normalisation and augmentation techniques. Brain extraction, as a preprocessing step, can improve the accuracy of an algorithm for abnormality classification in MRI image slices.
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