Identifying patients with multiple sclerosis (pwMS) at higher risk of clinical progression is essential to inform clinical management. We aimed to build prognostic models using machine learning (ML) algorithms predicting long-term clinical outcomes based on a systematic mapping of volumetric, radiomic, and macrostructural disconnection features from routine brain MRI scans of pwMS. In this longitudinal monocentric study, 3T structural MRI scans of pwMS were retrospectively analyzed. Based on a ten-year clinical follow-up (average duration=9.4±1.1 years), patients were classified according to confirmed disability progression (CDP) and cognitive impairment (CI) as assessed through the Expanded Disability Status Scale (EDSS) and the Brief International Cognitive Assessment of Multiple Sclerosis (BICAMS) battery, respectively. 3D-T1w and FLAIR images were automatically segmented to obtain volumes, disconnection scores (estimated based on lesion masks and normative tractography data), and radiomic features from 116 gray matter regions defined according to the Automated Anatomical Labelling (AAL) atlas. Three ML algorithms (Extra Trees, Logistic Regression, and Support Vector Machine) were used to build models predicting long-term CDP and CI based on MRI-derived features. Feature selection was performed on the training set with a multi-step process, and models were validated with a holdout approach, randomly splitting the patients into training (75%) and test (25%) sets. We studied 177 pwMS (M/F = 51/126; mean±SD age: 35.2±8.7 years). Long-term CDP and CI were observed in 71 and 55 patients, respectively. Regarding the CDP class prediction analysis, the feature selection identified 13-, 12-, and 10-feature subsets obtaining an accuracy on the test set of 0.71, 0.69, and 0.67 for the Extra Trees, Logistic Regression, and Support Vector Machine classifiers, respectively. Similarly, for the CI prediction, subsets of 16, 17, and 19 features were selected, with 0.69, 0.64, and 0.62 accuracy values on the test set, respectively. There were no significant differences in accuracy between ML models for CDP (p=0.65) or CI (p=0.31). Building on quantitative features derived from conventional MRI scans, we obtained long-term prognostic models, potentially informing patients' stratification and clinical decision-making. MS, multiple sclerosis; pwMS, people with MS; HC, healthy controls; ML, machine learning; DD, disease duration; EDSS, Expanded Disability Status Scale; TLV, total lesion volume; CDP, confirmed disability progression; CI, cognitive impairment; BICAMS, Brief International Cognitive Assessment of Multiple Sclerosis.

This study aimed to develop an interpretable, domain-generalizable deep learning model for microvascular invasion (MVI) assessment in hepatocellular carcinoma (HCC). Utilizing a retrospective dataset of 546 HCC patients from five centers, we developed and validated a clinical-radiological model and deep learning models aimed at MVI prediction. The models were developed on a dataset of 263 cases consisting of data from three centers, internally validated on a set of 66 patients, and externally tested on two independent sets. An adversarial network-based deep learning (AD-DL) model was developed to learn domain-invariant features from multiple centers within the training set. The area under the receiver operating characteristic curve (AUC) was calculated using pathological MVI status. With the best-performed model, early recurrence-free survival (ERFS) stratification was validated on the external test set by the log-rank test, and the differentially expressed genes (DEGs) associated with MVI status were tested on the RNA sequencing analysis of the Cancer Imaging Archive. The AD-DL model demonstrated the highest diagnostic performance and generalizability with an AUC of 0.793 in the internal test set, 0.801 in external test set 1, and 0.773 in external test set 2. The model's prediction of MVI status also demonstrated a significant correlation with ERFS (p = 0.048). DEGs associated with MVI status were primarily enriched in the metabolic processes and the Wnt signaling pathway, and the epithelial-mesenchymal transition process. The AD-DL model allows preoperative MVI prediction and ERFS stratification in HCC patients, which has a good generalizability and biological interpretability. The adversarial network-based deep learning model predicts MVI status well in HCC patients and demonstrates good generalizability. By integrating bioinformatics analysis of the model's predictions, it achieves biological interpretability, facilitating its clinical translation. Current MVI assessment models for HCC lack interpretability and generalizability. The adversarial network-based model's performance surpassed clinical radiology and squeeze-and-excitation network-based models. Biological function analysis was employed to enhance the interpretability and clinical translatability of the adversarial network-based model.

Early-onset Alzheimer's disease (EOAD) population is a clinically, genetically and pathologically heterogeneous condition. Identifying biomarkers related to disease progression is crucial for advancing clinical trials and improving therapeutic strategies. This study aims to differentiate EOAD patients with varying rates of progression using Brain Age Gap Estimation (BrainAGE)-based clustering algorithm applied to structural magnetic resonance images (MRI). A retrospective analysis of a longitudinal cohort consisting of 142 participants who met the criteria for early-onset probable Alzheimer's disease was conducted. Participants were assessed clinically, neuropsychologically and with structural MRI at baseline and annually for 6 years. A Brain Age Gap Estimation (BrainAGE) deep learning model pre-trained on 3,227 3D T1-weighted MRI of healthy subjects was used to extract encoded MRI representations at baseline. Then, k-means clustering was performed on these encoded representations to stratify the population. The resulting clusters were then analyzed for disease severity, cognitive phenotype and brain volumes at baseline and longitudinally. The optimal number of clusters was determined to be 2. Clusters differed significantly in BrainAGE scores (5.44 [± 8] years vs 15.25 [± 5 years], p < 0.001). The high BrainAGE cluster was associated with older age (p = 0.001) and higher proportion of female patients (p = 0.005), as well as greater disease severity based on Mini Mental State Examination (MMSE) scores (19.32 [±4.62] vs 14.14 [±6.93], p < 0.001) and gray matter volume (0.35 [±0.03] vs 0.32 [±0.02], p < 0.001). Longitudinal analyses revealed significant differences in disease progression (MMSE decline of -2.35 [±0.15] pts/year vs -3.02 [±0.25] pts/year, p = 0.02; CDR 1.58 [±0.10] pts/year vs 1.99 [±0.16] pts/year, p = 0.03). K-means clustering of BrainAGE encoded representations stratified EOAD patients based on varying rates of disease progression. These findings underscore the potential of using BrainAGE as a biomarker for better understanding and managing EOAD.

Deep complex convolutional networks (DCCNs) utilize complex-valued convolutions and can process complex-valued MRI signals directly without splitting them into two real-valued magnitude and phase components. The performance of DCCN and real-valued U-Net is thoroughly investigated in the physics-informed subject-specific ad-hoc reconstruction method for fat-water separation and is compared against a widely used reference approach. A comprehensive test dataset (n = 33) was used for performance analysis. The 2012 ISMRM fat-water separation workshop dataset containing 28 batches of multi-echo MRIs with 3-15 echoes from the abdomen, thigh, knee, and phantoms, acquired with 1.5 T and 3 T scanners were used. Additionally, five MAFLD patients multi-echo MRIs acquired from our clinical radiology department were also used. The quantitative results demonstrated that DCCN produced fat-water maps with better normalized RMS error and structural similarity index with the reference approach, compared to real-valued U-Nets in the ad-hoc reconstruction method for fat-water separation. The DCCN achieved an overall average SSIM of 0.847 ± 0.069 and 0.861 ± 0.078 in generating fat and water maps, respectively, in contrast the U-Net achieved only 0.653 ± 0.166 and 0.729 ± 0.134. The average liver PDFF from DCCN achieved a correlation coefficient R of 0.847 with the reference approach.

Mental processing delineates the functions of human mind encompassing a wide range of motor, sensory, emotional, and cognitive processes, each of which is underlain by the neuroanatomical substrates. Identifying accurate representation of functional neuroanatomy substrates of mental processing could inform understanding of its neural mechanism. The challenge is that it is unclear whether a specific mental process possesses a 'functional neuroanatomy fingerprint', i.e., a unique and reliable pattern of functional neuroanatomy that underlies the mental process. To address this question, we utilized a multi-task deep learning model to disentangle the functional neuroanatomy fingerprint of seven different and representative mental processes including Emotion, Gambling, Language, Motor, Relational, Social, and Working Memory. Results based on the functional magnetic resonance imaging data of two independent cohorts of 1235 subjects from the US and China consistently show that each of the seven mental processes possessed a functional neuroanatomy fingerprint, which is represented by a unique set of functional activity weights of whole-brain regions characterizing the degree of each region involved in the mental process. The functional neuroanatomy fingerprint of a specific mental process exhibits high discrimination ability (93% classification accuracy and AUC of 0.99) with those of the other mental processes, and is robust across different datasets and using different brain atlases. This study provides a solid functional neuroanatomy foundation for investigating the neural mechanism of mental processing.

Recent advances in the treatment of acute ischemic stroke contribute to improved patient outcomes, yet the mechanisms driving long-term disease trajectory are not well-understood. Current trends in the literature emphasize the distributed disruptive impact of stroke lesions on brain network organization. While most studies use population-derived data to investigate lesion interference on healthy tissue, the potential for individualized treatment strategies remains underexplored due to a lack of availability and effective utilization of the necessary clinical imaging data. To validate the potential for individualized patient evaluation, we explored and compared the differential information in network models based on normative and individual data. We further present our novel deep learning approach providing usable and accurate estimates of individual stroke impact utilizing minimal imaging data, thus bridging the data gap hindering individualized treatment planning. We created normative and individual disconnectomes for each of 78 patients (mean age 65.1 years, 32 females) from two independent cohort studies. MRI data and Barthel Index, as a measure of activities of daily living, were collected in the acute and early sub-acute phase after stroke (baseline) and at three months post stroke incident. Disconnectomes were subsequently described using 12 network metrics, including clustering coefficient and transitivity. Metrics were first compared between disconnectomes and further utilized as features in a classifier to predict a patients disease trajectory, as defined by three months Barthel Index. We then developed a deep learning architecture based on graph convolution and trained it to predict properties of the individual disconnectomes from the normative disconnectomes. Both disconnectomes showed statistically significant differences in topology and predictive power. Normative disconnectomes included a statistically significant larger number of connections (N=604 for normative versus N=210 for individual) and agreement between network properties ranged from r2=0.01 for clustering coefficient to r2=0.8 for assortativity, highlighting the impact of disconnectome choice on subsequent analysis. To predict patient deficit severity, individual data achieved an AUC score of 0.94 compared to an AUC score of 0.85 for normative based features. Our deep learning estimates showed high correlation with individual features (mean r2=0.94) and a comparable performance with an AUC score of 0.93. We were able to show how normative data-based analysis of stroke disconnections provides limited information regarding patient recovery. In contrast, individual data provided higher prognostic precision. We presented a novel approach to curb the need for individual data while retaining most of the differential information encoding individual patient disease trajectory.

Functional magnetic resonance imaging (fMRI) is a powerful tool for non-invasive evaluation of micro-changes in the kidneys. This study aims to develop classification and prognostic models based on multi-modal data. A total of 172 participants were included, and high-resolution multi-parameter fMRI technology was employed to obtain T2-weighted imaging (T2WI), blood oxygen level dependent (BOLD), and diffusion tensor imaging (DTI) sequence images. Based on clinical indicators, fMRI markers, serum and urine biomarkers (CD300LF, CST4, MMRN2, SERPINA1, l-glutamic acid dimethyl ester and phosphatidylcholine), machine learning algorithms were applied to establish and validate classification diagnosis models (Models 1-6) and risk-prognostic models (Models A-E). Additionally, accuracy, sensitivity, specificity, precision, area under the curve (AUC) and recall were used to evaluate the predictive performance of the models. A total of six classification models were established. Model 5 (fMRI + clinical indicators) exhibited superior performance, with an accuracy of 0.833 (95% confidence interval [CI]: 0.653-0.944). Notably, the multi-modal model incorporating image, serum and urine multi-omics and clinical indicators (Model 6) demonstrated higher predictive performance, achieving an accuracy of 0.923 (95% CI: 0.749-0.991). Furthermore, a total of five prognostic models at 2-year and 3-year follow-up were established. The Model E exhibited superior performance, achieving AUC values of 0.975 at the 2-year follow-up and 0.932 at the 3-year follow-up. Furthermore, Model E can identify patients with a high-risk prognosis. In clinical practice, the multi-modal models presented in this study demonstrate potential to enhance clinical decision-making capabilities regarding patient classification and prognosis prediction.

To construct and validate the optimal model for preoperative prediction of proliferative HCC based on habitat-derived radiomics features of Gd-EOB-DTPA-Enhanced MRI. A total of 187 patients who underwent Gd-EOB-DTPA-enhanced MRI before curative partial hepatectomy were divided into training (n=130, 50 proliferative and 80 nonproliferative HCC) and validation cohort (n=57, 25 proliferative and 32 nonproliferative HCC). Habitat subregion generation was performed using the Gaussian Mixture Model (GMM) clustering method to cluster all pixels to identify similar subregions within the tumor. Radiomic features were extracted from each tumor subregion in the arterial phase (AP) and hepatobiliary phase (HBP). Independent sample t tests, Pearson correlation coefficient, and Least Absolute Shrinkage and Selection Operator (LASSO) algorithm were performed to select the optimal features of subregions. After feature integration and selection, machine-learning classification models using the sci-kit-learn library were constructed. Receiver Operating Characteristic (ROC) curves and the DeLong test were performed to compare the identified performance for predicting proliferative HCC among these models. The optimal number of clusters was determined to be 3 based on the Silhouette coefficient. 20, 12, and 23 features were retained from the AP, HBP, and the combined AP and HBP habitat (subregions 1, 2, 3) radiomics features. Three models were constructed with these selected features in AP, HBP, and the combined AP and HBP habitat radiomics features. The ROC analysis and DeLong test show that the Naive Bayes model of AP and HBP habitat radiomics (AP-HBP-Hab-Rad) archived the best performance. Finally, the combined model using the Light Gradient Boosting Machine (LightGBM) algorithm, incorporating the AP-HBP-Hab-Rad, age, and AFP (Alpha-Fetoprotein), was identified as the optimal model for predicting proliferative HCC. For the training and validation cohort, the accuracy, sensitivity, specificity, and AUC were 0.923, 0.880, 0.950, 0.966 (95% CI: 0.937-0.994) and 0.825, 0.680, 0.937, 0.877 (95% CI: 0.786-0.969), respectively. In its validation cohort of the combined model, the AUC value was statistically higher than the other models (P<0.01). A combined model, including AP-HBP-Hab-Rad, serum AFP, and age using the LightGBM algorithm, can satisfactorily predict proliferative HCC preoperatively.

To develop a machine learning-based predictive model for local recurrence after radiotherapy in patients with gliomas, with interpretability enhanced through SHapley Additive exPlanations (SHAP). We retrospectively enrolled 145 patients with pathologically confirmed gliomas who underwent brain radiotherapy (training: validation = 102:43). Physiological and structural magnetic resonance imaging (MRI) were used to define habitat regions. A total of 2153 radiomic features were extracted from each MRI sequence in each habitat region, respectively. Relief and Recursive Feature Elimination were used for radiomic feature selection. Support vector machine (SVM) and random forest models incorporating clinical and radiomic features were constructed for each habitat region. The SHAP method was used to explain the predictive model. In the training cohort and validation cohort, the Physiological_Habitat1 (e-THRIVE)_radiomic SVM model demonstrated the best AUC of 0.703 (95% CI 0.569-0.836) and 0.670 (95% CI 0.623-0.717) compared to the other radiomic models. The SHAP summary plot and SHAP force plot were used to interpret the best-performing Physiological_Habitat1 (e-THRIVE)_radiomic SVM model. Radiomic features derived from the Physiological_Habitat1 (e-THRIVE) were predictive of local recurrence in glioma patients following radiotherapy. The SHAP method provided insights into how the tumor microenvironment might influence the effectiveness of radiotherapy in postoperative gliomas.

Accurate segmentation of white matter hyperintensities (WMH) is crucial for clinical decision-making, particularly in the context of multiple sclerosis. However, domain shifts, such as variations in MRI machine types or acquisition parameters, pose significant challenges to model calibration and uncertainty estimation. This comparative study investigates the impact of domain shift on WMH segmentation, proposing maximum-entropy regularization techniques to enhance model calibration and uncertainty estimation. The purpose is to identify errors appearing after model deployment in clinical scenarios using predictive uncertainty as a proxy measure, since it does not require ground-truth labels to be computed. We conducted experiments using a classic U-Net architecture and evaluated maximum entropy regularization schemes to improve model calibration under domain shift on two publicly available datasets: the WMH Segmentation Challenge and the 3D-MR-MS dataset. Performance is assessed with Dice coefficient, Hausdorff distance, expected calibration error, and entropy-based uncertainty estimates. Entropy-based uncertainty estimates can anticipate segmentation errors, both in-distribution and out-of-distribution, with maximum-entropy regularization further strengthening the correlation between uncertainty and segmentation performance, while also improving model calibration under domain shift. Maximum-entropy regularization improves uncertainty estimation for WMH segmentation under domain shift. By strengthening the relationship between predictive uncertainty and segmentation errors, these methods allow models to better flag unreliable predictions without requiring ground-truth annotations. Additionally, maximum-entropy regularization contributes to better model calibration, supporting more reliable and safer deployment of deep learning models in multi-center and heterogeneous clinical environments.