Traumatic Brain Injury (TBI) is a global health concern, with mild TBI (mTBI) being the most common form. Despite its prevalence, accurately diagnosing mTBI remains a significant challenge. While advanced neuroimaging techniques like diffusion tensor imaging (DTI) offer promise for more robust diagnosis, their clinical application is limited by inconsistent and heterogeneous post-injury findings. Recently, machine learning (ML) techniques, utilizing DTI metrics as features, have shown increasing utility in mTBI research. This approach helps identify distinct between-group features, paving the way for more precise and efficient diagnostic and prognostic tools. This review aims to analyze studies employing ML techniques to assess changes in DTI metrics after mTBI. Systematic review. We conducted a systematic review, adhering to PRISMA guidelines, on the application of ML with DTI for mTBI diagnosis and prognosis on human subjects. This review identified 36 articles. N/A. Study quality was assessed using the Modified QualSyst Assessment Tool. N/A. The review found ML techniques using DTI Metrics either alone or in combination with other modalities (i.e., structural MRI, functional MRI, clinical scores, or demographics) can effectively classify mTBI patients from controls. These approaches have also demonstrated potential in classifying mTBI patients according to the degree of recovery and symptom severity. In addition, these ML models showed strong predictive power toward cognitive scores and brain structural decline, as quantified by brain-predicted age difference. Larger, externally validated studies are needed to develop robust models for the diagnosis and prognosis of mTBI, using imaging biomarkers (including DTI) in conjunction with non-imaging, on-field, or clinical data. Despite the high predictive performance of ML algorithms, the clinical application remains distant, likely due to the small sample size of studies and lack of external validation, which raises concerns about overfitting. 5. Stage 1.

Bottom-of-sulcus dysplasia (BOSD) is a diagnostically challenging subtype of focal cortical dysplasia, 60% being missed on magnetic resonance imaging (MRI). Automated MRI-based detection methods have been developed for focal cortical dysplasia, but not BOSD specifically, and few methods incorporate fluorodeoxyglucose positron emission tomography (FDG-PET) alongside MRI features. We report the development and performance of an automated BOSD detector using combined MRI + PET. The training set comprised 54 patients with focal epilepsy and BOSD. The test sets comprised 17 subsequently diagnosed patients with BOSD from the same center, and 12 published patients from a different center. Across training and test sets, 81% of patients had normal initial MRIs and most BOSDs were <1.5 cm³. In the training set, 12 features from T1-MRI, fluid-attenuated inversion recovery-MRI, and FDG-PET were evaluated to determine which features best distinguished dysplastic from normal-appearing cortex. Using the Multi-centre Epilepsy Lesion Detection group's machine-learning detection method with the addition of FDG-PET, neural network classifiers were then trained and tested on MRI + PET, MRI-only, and PET-only features. The proportion of patients whose BOSD was overlapped by the top output cluster, and the top five output clusters, were determined. Cortical and subcortical hypometabolism on FDG-PET was superior in discriminating dysplastic from normal-appearing cortex compared to MRI features. When the BOSD detector was trained on MRI + PET features, 87% BOSDs were overlapped by one of the top five clusters (69% top cluster) in the training set, 94% in the prospective test set (88% top cluster), and 75% in the published test set (58% top cluster). Cluster overlap was generally lower when the detector was trained and tested on PET-only or MRI-only features. Detection of BOSD is possible using established MRI-based automated detection methods, supplemented with FDG-PET features and trained on a BOSD-specific cohort. In clinically appropriate patients with seemingly negative MRI, the detector could suggest MRI regions to scrutinize for possible BOSD.

Amyloid PET/CT is essential for quantifying amyloid-beta (Aβ) deposition in Alzheimer's disease (AD), with the Centiloid (CL) scale standardizing measurements across imaging centers. However, MRI-based CL pipelines face challenges: high cost, contraindications, and patient burden. To address these challenges, we developed a deep learning-based CT parcellation pipeline calibrated to the standard CL scale using CT images from PET/CT scans and evaluated its performance relative to standard pipelines. A total of 306 participants (23 young controls [YCs] and 283 patients) underwent 18 F-florbetaben (FBB) PET/CT and MRI. Based on visual assessment, 207 patients were classified as Aβ-positive and 76 as Aβ-negative. PET images were processed using the CT parcellation pipeline and compared to FreeSurfer (FS) and standard pipelines. Agreement was assessed via regression analyses. Effect size, variance, and ROC analyses were used to compare pipelines and determine the optimal CL threshold relative to visual Aβ assessment. The CT parcellation showed high concordance with the FS and provided reliable CL quantification (R² = 0.99). Both pipelines demonstrated similar variance in YCs and effect sizes between YCs and ADCI. ROC analyses confirmed comparable accuracy and similar CL thresholds, supporting CT parcellation as a viable MRI-free alternative. Our findings indicate that the CT parcellation pipeline achieves a level of accuracy similar to FS in CL quantification, demonstrating its reliability as an MRI-free alternative. In PET/CT, CT and PET are acquired sequentially within the same session on a shared bed and headrest, which helps maintain consistent positioning and adequate spatial alignment, reducing registration errors and supporting more reliable and precise quantification.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in substantia nigra, resulting in both motor impairments and cognitive decline. Traditional PD classification methods are expert-dependent and time-intensive, while existing deep learning (DL) models often suffer from inconsistent accuracy, limited interpretability, and inability to fully capture PD's clinical heterogeneity. This study proposes a novel framework Enhanced EfficientNet-Extended Multimodal PD Classification with Hybrid Particle Swarm and Grey Wolf Optimizer (EEFN-XM-PDC-HybPS-GWO) to overcome these challenges. The model integrates T1-weighted MRI, DaTscan images, and gait scores from NTUA and PhysioNet repository respectively. Denoising is achieved via Multiscale Attention Variational Autoencoders (MSA-VAE), and critical regions are segmented using Semantic Invariant Multi-View Clustering (SIMVC). The Enhanced EfficientNet-Extended Multimodal (EEFN-XM) model extracts and fuses image and gait features, while HybPS-GWO optimizes classification weights. The system classifies subjects into early-stage PD, advanced-stage PD, and healthy controls (HCs). Ablation analysis confirms the hybrid optimizer's contribution to performance gains. The proposed model achieved 99.2% accuracy with stratified 5-fold cross-validation, outperforming DMFEN-PDC, MMT-CA-PDC, and LSTM-PDD-GS by 7.3%, 15.97%, and 10.43%, respectively, and reduced execution time by 33.33%. EEFN-XM-PDC-HybPS-GWO demonstrates superior accuracy, computational efficiency, and clinical relevance, particularly in early-stage diagnosis and PD classification.

We introduce mpLLM, a prompt-conditioned hierarchical mixture-of-experts (MoE) architecture for visual question answering over multi-parametric 3D brain MRI (mpMRI). mpLLM routes across modality-level and token-level projection experts to fuse multiple interrelated 3D modalities, enabling efficient training without image--report pretraining. To address limited image-text paired supervision, mpLLM integrates a synthetic visual question answering (VQA) protocol that generates medically relevant VQA from segmentation annotations, and we collaborate with medical experts for clinical validation. mpLLM outperforms strong medical VLM baselines by 5.3% on average across multiple mpMRI datasets. Our study features three main contributions: (1) the first clinically validated VQA dataset for 3D brain mpMRI, (2) a novel multimodal LLM that handles multiple interrelated 3D modalities, and (3) strong empirical results that demonstrate the medical utility of our methodology. Ablations highlight the importance of modality-level and token-level experts and prompt-conditioned routing. We have included our source code in the supplementary materials and will release our dataset upon publication.

Quantification of amyloid plaques (A), neurofibrillary tangles (T₂), and neurodegeneration (N) using PET and MRI is critical for Alzheimer's disease (AD) diagnosis and prognosis. Existing pipelines face limitations regarding processing time, tracer variability handling, and multimodal integration. We developed petBrain, a novel end-to-end processing pipeline for amyloid-PET, tau-PET, and structural MRI. It leverages deep learning-based segmentation, standardized biomarker quantification (Centiloid, CenTauR, HAVAs), and simultaneous estimation of A, T₂, and N biomarkers. It is implemented in a web-based format, requiring no local computational infrastructure and software usage knowledge. petBrain provides reliable, rapid quantification with results comparable to existing pipelines for A and T₂, showing strong concordance with data processed in ADNI databases. The staging and quantification of A/T₂/N by petBrain demonstrated good agreements with CSF/plasma biomarkers, clinical status and cognitive performance. petBrain represents a powerful open platform for standardized AD biomarker analysis, facilitating clinical research applications.

<i>Objective.</i>Alzheimer's disease (AD) is the most prevalent form of dementia worldwide, encompassing a prodromal stage known as mild cognitive impairment (MCI), where patients may either progress to AD or remain stable. The objective of the work was to capture structural and functional modulations of brain structure and function relying on multimodal MRI data and single nucleotide polymorphisms, also in case of missing views, with the twofold goal of classifying AD patients versus healthy controls and detecting MCI converters.<i>Approach.</i>We propose a multimodal deep learning (DL)-based classification framework where a generative module employing cycle generative adversarial networks was introduced in the latent space for imputing missing data (a common issue of multimodal approaches). Explainable AI method was then used to extract input features' relevance allowing for post-hoc validation and enhancing the interpretability of the learned representations.<i>Main results.</i>Experimental results on two tasks, AD detection and MCI conversion, showed that our framework reached competitive performance in the state-of-the-art with an accuracy of0.926±0.02(CI [0.90, 0.95]) and0.711±0.01(CI [0.70, 0.72]) in the two tasks, respectively. The interpretability analysis revealed gray matter modulations in cortical and subcortical brain areas typically associated with AD. Moreover, impairments in sensory-motor and visual resting state networks along the disease continuum, as well as genetic mutations defining biological processes linked to endocytosis, amyloid-beta, and cholesterol, were identified.<i>Significance.</i>Our integrative and interpretable DL approach shows promising performance for AD detection and MCI prediction while shedding light on important biological insights.

The brain tumour (BT) is an aggressive disease among others, which leads to a very short life expectancy. Therefore, early and prompt treatment is the main stage in enhancing patients' quality of life. Biomedical imaging permits the non-invasive evaluation of diseases, depending upon visual assessments that lead to better medical outcome expectations and therapeutic planning. Numerous image techniques like computed tomography (CT), magnetic resonance imaging (MRI), etc., are employed for evaluating cancer in the brain. The detection, segmentation and extraction of diseased tumour regions from biomedical images are a primary concern, but are tiresome and time-consuming tasks done by clinical specialists, and their outcome depends on their experience only. Therefore, the use of computer-aided technologies is essential to overcoming these limitations. Recently, artificial intelligence (AI) models have been very effective in enhancing performance and improving the method of medical image diagnosis. This paper proposes an Enhanced Brain Tumour Segmentation through Biomedical Imaging and Feature Model Fusion with Bonobo Optimiser (EBTS-BIFMFBO) model. The main intention of the EBTS-BIFMFBO model relies on enhancing the segmentation and classification model of BTs utilizing advanced models. Initially, the EBTS-BIFMFBO technique follows bilateral filter (BF)-based noise elimination and CLAHE-based contrast enhancement. Furthermore, the proposed EBTS-BIFMFBO model involves a segmentation process by the DeepLabV3 + model to identify tumour regions for accurate diagnosis. Moreover, the fusion models such as InceptionResNetV2, MobileNet, and DenseNet201 are employed for the feature extraction. Additionally, the convolutional sparse autoencoder (CSAE) method is implemented for the classification process of BT. Finally, the hyper-parameter selection of CSAE is performed by the bonobo optimizer (BO) method. A vast experiment is conducted to highlight the performance of the EBTS-BIFMFBO approach under the Figshare BT dataset. The comparison results of the EBTS-BIFMFBO approach portrayed a superior accuracy value of 99.16% over existing models.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) pose significant challenges to public health and underscore the need for accurate and early diagnostic tools. Structural magnetic resonance imaging (sMRI) combined with advanced analytical techniques like convolutional neural networks (CNNs) seemed to offer a promising avenue for the diagnosis of these conditions. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of CNN algorithms applied to sMRI data in differentiating between AD, MCI, and normal cognition (NC). Following the PRISMA-DTA guidelines, a comprehensive literature search was carried out in PubMed and Web of Science databases for studies published between 2018 and 2024. Studies were included if they employed CNNs for the diagnostic classification of sMRI data from participants with AD, MCI, or NC. The methodological quality of the included studies was assessed using the QUADAS-2 and METRICS tools. Data extraction and statistical analysis were performed to calculate pooled diagnostic accuracy metrics. A total of 21 studies were included in the study, comprising 16,139 participants in the analysis. The pooled sensitivity and specificity of CNN algorithms for differentiating AD from NC were 0.92 and 0.91, respectively. For distinguishing MCI from NC, the pooled sensitivity and specificity were 0.74 and 0.79, respectively. The algorithms also showed a moderate ability to differentiate AD from MCI, with a pooled sensitivity and specificity of 0.73 and 0.79, respectively. In the pMCI versus sMCI classification, a pooled sensitivity was 0.69 and a specificity was 0.81. Heterogeneity across studies was significant, as indicated by meta-regression results. CNN algorithms demonstrated promising diagnostic performance in differentiating AD, MCI, and NC using sMRI data. The highest accuracy was observed in distinguishing AD from NC and the lowest accuracy observed in distinguishing pMCI from sMCI. These findings suggest that CNN-based radiomics has the potential to serve as a valuable tool in the diagnostic armamentarium for neurodegenerative diseases. However, the heterogeneity among studies indicates a need for further methodological refinement and validation. This systematic review was registered in PROSPERO (Registration ID: CRD42022295408).

Multiple sclerosis (MS) remains a complex and costly neurological condition characterised by progressive disability, making early detection and accurate prognosis of disease progression imperative. While artificial intelligence (AI) combined with big data promises transformative advances in personalised MS care, integration of multimodal, real-world datasets, including clinical records, magnetic resonance imaging (MRI), and digital biomarkers, remains limited. This perspective paper identifies a critical gap between technical innovation and clinical implementation, driven by methodological constraints, evolving regulatory frameworks, and ethical concerns related to bias, privacy, and equity. We explore this gap through three interconnected lenses: the underuse of integrated real-world data, the barriers posed by regulation and ethics, and emerging solutions. Promising strategies such as federated learning, regulatory initiatives like DARWIN-EU and the European Health Data Space, and patient-led frameworks including PROMS and CLAIMS, offer structured pathways forward. Additionally, we highlight the growing relevance of foundation models for interpreting complex MS data and supporting clinical decision-making. We advocate for harmonised data infrastructures, patient-centred design, explainable AI, and real-world validation as core pillars for future implementation. By aligning technical, regulatory, and ethical domains, stakeholders can unlock the full potential of AI to enhance prognosis, personalise care, and improve outcomes for people with MS.