Degenerative cerebellar ataxia, a group of progressive neurodegenerative disorders, is characterised by cerebellar atrophy and impaired motor learning. Using CerebNet, a deep learning algorithm for cerebellar segmentation, this study investigated the relationship between cerebellar subregion volumes and motor learning ability. We analysed data from 37 patients with degenerative cerebellar ataxia and 18 healthy controls. Using CerebNet, we segmented four cerebellar subregions: the anterior lobe, superior posterior lobe, inferior posterior lobe, and vermis. Regression analyses examined the associations between cerebellar volumes and motor learning performance (adaptation index [AI]) and ataxia severity (Scale for Assessment and Rating of Ataxia [SARA]). The inferior posterior lobe volume showed a significant positive association with AI in both single (B = 0.09; 95% CI: [0.03, 0.16]) and multiple linear regression analyses (B = 0.11; 95% CI: [0.008, 0.20]), an association that was particularly evident in the pure cerebellar ataxia subgroup. SARA scores correlated with anterior lobe, superior posterior lobe, and vermis volumes in single linear regression analyses, but these associations were not maintained in multiple linear regression analyses. This selective association suggests a specialised role for the inferior posterior lobe in motor learning processes. This study reveals the inferior posterior lobe's distinct role in motor learning in patients with degenerative cerebellar ataxia, advancing our understanding of cerebellar function and potentially informing targeted rehabilitation approaches. Our findings highlight the value of advanced imaging technologies in understanding structure-function relationships in cerebellar disorders.

The relationship between mild neurovascular conflict (NVC) and trigeminal neuralgia (TN) remains ill-defined, especially as mild NVC is often seen in asymptomatic population without any facial pain. We aim to analyze the trigeminal nerve microstructure using artificial intelligence (AI) to distinguish symptomatic and asymptomatic nerves between idiopathic TN (iTN) and the asymptomatic control group with incidental grade‑1 NVC. Seventy-eight symptomatic trigeminal nerves with grade-1 NVC in iTN patients, and an asymptomatic control group consisting of Bell's palsy patients free from facial pain (91 grade-1 NVC and 91 grade-0 NVC), were included in the study. Three hundred seventy-eight radiomic features were extracted from the original MRI images and processed with Laplacian-of-Gaussian filters. The dataset was split into 80% training/validation and 20% testing. Nested cross-validation was employed on the training/validation set for feature selection and model optimization. Furthermore, using the same pipeline approach, two customized deep learning models, Dense Atrous Spatial Pyramid Pooling (ASPP) -201 and MobileASPPV2, were classified using the same pipeline approach, incorporating ASPP blocks. Performance was assessed over ten and five runs for radiomics-based and deep learning-based models. Subspace Discriminant Ensemble Learning (SDEL) attained an accuracy of 78.8%±7.13%, Support Vector Machines (SVM) reached 74.8%±9.2%, and K-nearest neighbors (KNN) achieved 79%±6.55%. Meanwhile, DenseASPP-201 recorded an accuracy of 82.0 ± 8.4%, and MobileASPPV2 achieved 73.2 ± 5.59%. The AI effectively distinguished symptomatic and asymptomatic nerves with grade‑1 NVC. Further studies are required to fully elucidate the impact of vascular and nonvascular etiologies that may lead to iTN.

The fifth edition of the World Health Organization classification of central nervous system tumors represents a significant advancement in the molecular-genetic classification of pediatric-type diffuse gliomas. This article comprehensively summarizes the clinical, molecular, and radiological imaging features in pediatric-type low-grade gliomas (pLGGs), including MYB- or MYBL1-altered tumors, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and diffuse low-grade glioma, MAPK pathway-altered. Most pLGGs harbor alterations in the RAS/MAPK pathway, functioning as "one pathway disease". Specific magnetic resonance imaging features, such as the T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign in MYB- or MYBL1-altered tumors and the transmantle-like sign in PLNTYs, may serve as non-invasive biomarkers for underlying molecular alterations. Recent advances in radiogenomics have enabled the differentiation of BRAF fusion from BRAF V600E mutant tumors based on magnetic resonance imaging characteristics. Machine learning approaches have further enhanced our ability to predict molecular subtypes from imaging features. These radiology-molecular correlations offer potential clinical utility in treatment planning and prognostication, especially as targeted therapies against the MAPK pathway emerge. Continued research is needed to refine our understanding of genotype-phenotype correlations in less common molecular alterations and to validate these imaging biomarkers in larger cohorts.

Cortical lesions (CLs) have emerged as valuable biomarkers in multiple sclerosis (MS), offering high diagnostic specificity and prognostic relevance. However, their routine clinical integration remains limited due to subtle magnetic resonance imaging (MRI) appearance, challenges in expert annotation, and a lack of standardized automated methods. We propose a comprehensive multi-centric benchmark of CL detection and segmentation in MRI. A total of 656 MRI scans, including clinical trial and research data from four institutions, were acquired at 3T and 7T using MP2RAGE and MPRAGE sequences with expert-consensus annotations. We rely on the self-configuring nnU-Net framework, designed for medical imaging segmentation, and propose adaptations tailored to the improved CL detection. We evaluated model generalization through out-of-distribution testing, demonstrating strong lesion detection capabilities with an F1-score of 0.64 and 0.5 in and out of the domain, respectively. We also analyze internal model features and model errors for a better understanding of AI decision-making. Our study examines how data variability, lesion ambiguity, and protocol differences impact model performance, offering future recommendations to address these barriers to clinical adoption. To reinforce the reproducibility, the implementation and models will be publicly accessible and ready to use at https://github.com/Medical-Image-Analysis-Laboratory/ and https://doi.org/10.5281/zenodo.15911797.

Magnetic Resonance Imaging (MRI) is widely recognized as the most reliable tool for detecting tumors due to its capability to produce detailed images that reveal their presence. However, the accuracy of diagnosis can be compromised when human specialists evaluate these images. Factors such as fatigue, limited expertise, and insufficient image detail can lead to errors. For example, small tumors might go unnoticed, or overlap with healthy brain regions could result in misidentification. To address these challenges and enhance diagnostic precision, this study proposes a novel double ensembling framework, consisting of ensembled pre-trained deep learning (DL) models for feature extraction and ensembled fine-tuned hyperparameter machine learning (ML) models to efficiently classify brain tumors. Specifically, our method includes extensive preprocessing and augmentation, transfer learning concepts by utilizing various pre-trained deep convolutional neural networks and vision transformer networks to extract deep features from brain MRI, and fine-tune hyperparameters of ML classifiers. Our experiments utilized three different publicly available Kaggle MRI brain tumor datasets to evaluate the pre-trained DL feature extractor models, ML classifiers, and the effectiveness of an ensemble of deep features along with an ensemble of ML classifiers for brain tumor classification. Our results indicate that the proposed feature fusion and classifier fusion improve upon the state of the art, with hyperparameter fine-tuning providing a significant enhancement over the ensemble method. Additionally, we present an ablation study to illustrate how each component contributes to accurate brain tumor classification.

Alzheimer's disease (AD) frequently co-occurs with depressive symptoms, exacerbating both cognitive decline and clinical complexity, yet the neural substrates linking this co-occurrence remain poorly understood. We aimed to investigate the role of basal forebrain-limbic system circuit dysregulation in the interaction between cognitive impairment and depressive symptoms, identifying potential biomarkers for early diagnosis and intervention. This cross-sectional study included participants stratified into normal controls (NC), cognitive impairment without depression (CI-nD), and cognitive impairment with depression (CI-D). Multimodal MRI (structural, diffusion, functional, perfusion, iron-sensitive imaging) and plasma biomarkers were analyzed. Machine learning models classified subgroups using neuroimaging features. CI-D exhibited distinct basal forebrain-limbic circuit alterations versus CI-nD and NC: (1) Elevated free-water fraction (FW) in basal forebrain subregions (Ch123/Ch4, p < 0.04), indicating early neuroinflammation; (2) Increased iron deposition in the anterior cingulate cortex and entorhinal cortex (p < 0.05); (3) Hyperperfusion and functional hyperactivity in Ch123 and amygdala; (4) Plasma neurofilamentlightchain exhibited correlated with hippocampal inflammation in CI-nD (p = 0.03) but linked to basal forebrain dysfunction in CI-D (p < 0.05). Multimodal support vector machine achieved 85 % accuracy (AUC=0.96) in distinguishing CI-D from CI-nD, with Ch123 and Ch4 as key discriminators. Pathway analysis in the CI-D group further revealed that FW-related neuroinflammation in the basal forebrain (Ch123/Ch4) indirectly contributed to cognitive impairment via structural atrophy. We identified a neuroinflammatory-cholinergic pathway in the basal forebrain as an early mechanism driving depression-associated cognitive decline. Multimodal imaging revealed distinct spatiotemporal patterns of circuit dysregulation, suggesting neuroinflammation and iron deposition precede structural degeneration. These findings position the basal forebrain-limbic system circuit as a therapeutic target and provide actionable biomarkers for early intervention in AD with depressive symptoms.

ImportanceBrain MRI is the main imaging modality for pediatric brain tumors (PBTs); however, incomplete MRI exams are common in pediatric neuro-oncology settings and pose a barrier to the development and application of deep learning (DL) models, such as tumor segmentation and prognostic risk estimation. ObjectiveTo evaluate DL-based strategies (image-dropout training and generative image synthesis) and heuristic imputation approaches for handling missing MRI sequences in PBT imaging from clinical acquisition protocols, and to determine their impact on segmentation accuracy and prognostic risk estimation. DesignThis cohort study included 715 patients from the Childrens Brain Tumor Network (CBTN) and BraTS-PEDs, and 43 patients with longitudinal MRI (157 timepoints) from PNOC003/007 clinical trials. We developed a dropout-trained nnU-Net tumor segmentation model that randomly omitted FLAIR and/or T1w (no contrast) sequences during training to simulate missing inputs. We compared this against three imputation approaches: a generative model for image synthesis, copy-substitution heuristics, and zeroed missing inputs. Model-generated tumor volumes from each segmentation method were compared and evaluated against ground truth (expert manual segmentations) and incorporated into time-varying Cox regression models for survival analysis. SettingMulti-institutional PBT datasets and longitudinal clinical trial cohorts. ParticipantsAll patients had multi-parametric MRI and expert manual segmentations. The PNOC cohort had a median of three imaging timepoints and associated clinical data. Main Outcomes and MeasuresSegmentation accuracy (Dice scores), image quality metrics for synthesized scans (SSIM, PSNR, MSE), and survival discrimination (C-index, hazard ratios). ResultsThe dropout model achieved robust segmentation under missing MRI, with [&le;]0.04 Dice drop and a stable C-index of 0.65 compared to complete-input performance. DL-based MRI synthesis achieved high image quality (SSIM > 0.90) and removed artifacts, benefiting visual interpretability. Performance was consistent across cohorts and missing data scenarios. Conclusion and RelevanceModality-dropout training yields robust segmentation and risk-stratification on incomplete pediatric MRI without the computational and clinical complexity of synthesis approaches. Image synthesis, though less effective for these tasks, provides complementary benefits for artifact removal and qualitative assessment of missing or corrupted MRI scans. Together, these approaches can facilitate broader deployment of AI tools in real-world pediatric neuro-oncology settings.

Major depressive disorder (MDD) is a highly prevalent mental health condition with significant public health implications. Early detection is crucial for timely intervention, but current diagnostic methods often rely on subjective clinical assessments, leading to delayed or inaccurate diagnoses. Advances in neuroimaging and machine learning (ML) offer the potential for objective and accurate early detection. This study aimed to develop and validate ML models using multisite functional magnetic resonance imaging data for the early detection of MDD, compare their performance, and evaluate their clinical applicability. We used functional magnetic resonance imaging data from 1200 participants (600 with early-stage MDD and 600 healthy controls) across 3 public datasets. In total, 4 ML models-support vector machine, random forest, gradient boosting machine, and deep neural network-were trained and evaluated using a 5-fold cross-validation framework. Models were assessed for accuracy, sensitivity, specificity, F1-score, and area under the receiver operating characteristic curve. Shapley additive explanations values and activation maximization techniques were applied to interpret model predictions. The deep neural network model demonstrated superior performance with an accuracy of 89% (95% CI 86%-92%) and an area under the receiver operating characteristic curve of 0.95 (95% CI 0.93-0.97), outperforming traditional diagnostic methods by 15% (P<.001). Key predictive features included altered functional connectivity between the dorsolateral prefrontal cortex, anterior cingulate cortex, and limbic regions. The model achieved 78% sensitivity (95% CI 71%-85%) in identifying individuals who developed MDD within a 2-year follow-up period, demonstrating good generalizability across datasets. Our findings highlight the potential of artificial intelligence-driven approaches for the early detection of MDD, with implications for improving early intervention strategies. While promising, these tools should complement rather than replace clinical expertise, with careful consideration of ethical implications such as patient privacy and model biases.

Glioma is the most common primary malignant brain tumor and preoperative genetic profiling is essential for the management of glioma patients. Our study focused on tumor regions segmentation and predicting the World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) mutation, and 1p/19q codeletion status using deep learning models on preoperative MRI. To achieve accurate tumor segmentation, we developed an optimal mass transport (OMT) approach to transform irregular MRI brain images into tensors. In addition, we proposed an algebraic preclassification (APC) model utilizing multimode OMT tensor singular value decomposition (SVD) to estimate preclassification probabilities. The fully automated deep learning model named OMT-APC was used for multitask classification. Our study incorporated preoperative brain MRI data from 3,565 glioma patients across 16 datasets spanning Asia, Europe, and America. Among these, 2,551 patients from 5 datasets were used for training and internal validation. In comparison, 1,014 patients from 11 datasets, including 242 patients from The Cancer Genome Atlas (TCGA), were used as independent external test. The OMT segmentation model achieved mean lesion-wise Dice scores of 0.880. The OMT-APC model was evaluated on the TCGA dataset, achieving accuracies of 0.855, 0.917, and 0.809, with AUC scores of 0.845, 0.908, and 0.769 for WHO grade, IDH mutation, and 1p/19q codeletion, respectively, which outperformed the four radiologists in all tasks. These results highlighted the effectiveness of our OMT and tensor SVD-based methods in brain tumor genetic profiling, suggesting promising applications for algebraic and geometric methods in medical image analysis.

High-quality 3D fetal brain MRI reconstruction from motion-corrupted 2D slices is crucial for precise clinical diagnosis and advancing our understanding of fetal brain development. This necessitates reliable slice-to-volume registration (SVR) for motion correction and super-resolution reconstruction (SRR) techniques. Traditional approaches have their limitations, but deep learning (DL) offers the potential in enhancing SVR and SRR. However, most of DL methods require large-scale external 3D high-resolution (HR) training datasets, which is challenging in clinical fetal MRI. To address this issue, we propose an unsupervised iterative joint SVR and SRR DL framework for 3D isotropic HR volume reconstruction. Specifically, our method conceptualizes SVR as a function that maps a 2D slice and a 3D target volume to a rigid transformation matrix, aligning the slice to the underlying location within the target volume. This function is parameterized by a convolutional neural network, which is trained by minimizing the difference between the volume slicing at the predicted position and the actual input slice. For SRR, a decoding network embedded within a deep image prior framework, coupled with a comprehensive image degradation model, is used to produce the HR volume. The deep image prior framework offers a local consistency prior to guide the reconstruction of HR volumes. By performing a forward degradation model, the HR volume is optimized by minimizing the loss between the predicted slices and the acquired slices. Experiments on both large-magnitude motion-corrupted simulation data and clinical data have shown that our proposed method outperforms current state-of-the-art fetal brain reconstruction methods. The source code is available at https://github.com/DeepBMI/SUFFICIENT.