Dementia is a complex condition whose multifaceted nature poses significant challenges in the diagnosis, prognosis, and treatment of patients. Despite the availability of large open-source data fueling a wealth of promising research, effective translation of preclinical findings to clinical practice remains difficult. This barrier is largely due to the complexity of unstructured and disparate preclinical and clinical data, which traditional analytical methods struggle to handle. Novel analytical techniques involving Deep Learning (DL), however, are gaining significant traction in this regard. Here, we have investigated the potential of a cascaded multimodal DL-based system (TelDem), assessing the ability to integrate and analyze a large, heterogeneous dataset (n=7,159 patients), applied to three clinically relevant use cases. Using a Cascaded Multi-Modal Mixing Transformer (CMT), we assessed TelDems validity and (using a Cross-Modal Fusion Norm - CMFN) model explainability in (i) differential diagnosis between healthy individuals, AD, and three sub-types of frontotemporal lobar degeneration (ii) disease staging from healthy cognition to mild cognitive impairment (MCI) and AD, and (iii) predicting progression from MCI to AD. Our findings show that the CMT enhances diagnostic and prognostic accuracy when incorporating multimodal data compared to unimodal modeling and that cerebrospinal fluid (CSF) biomarkers play a key role in accurate model decision making. These results reinforce the power of DL technology in tapping deeper into already existing data, thereby accelerating preclinical dementia research by utilizing clinically relevant information to disentangle complex dementia pathophysiology.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with heterogeneous symptomatology, making accurate diagnosis challenging. Traditional methods rely on subjective behavioral assessments, often overlooking subtle neural biomarkers. This study introduces ASD-GraphNet, a novel graph-based learning framework for diagnosing ASD using functional Magnetic Resonance Imaging (fMRI) data. Leveraging the Autism Brain Imaging Data Exchange (ABIDE) dataset, ASD-GraphNet constructs brain networks based on established atlases (Craddock 200, AAL, and Dosenbach 160) to capture intricate connectivity patterns. The framework employs systematic preprocessing, graph construction, and advanced feature extraction to derive node-level, edge-level, and graph-level metrics. Feature engineering techniques, including Mutual Information-based selection and Principal Component Analysis (PCA), are applied to enhance classification performance. ASD-GraphNet evaluates a range of classifiers, including Logistic Regression, Support Vector Machines, and ensemble methods like XGBoost and LightGBM, achieving an accuracy of 75.25% in distinguishing individuals with ASD from healthy controls. This demonstrates the framework's potential to provide objective, data-driven diagnostics based solely on resting-state fMRI data. By integrating graph-based learning with neuroimaging and addressing dataset imbalance, ASD-GraphNet offers a scalable and interpretable solution for early ASD detection, paving the way for more reliable interventions. The GitHub repository for this project is available at: https://github.com/AmirDavoodi/ASD-GraphNet.

Diffusion models have shown great promise in medical image denoising and reconstruction, but their application to Positron Emission Tomography (PET) imaging remains limited by tracer-specific contrast variability and high computational demands. In this work, we proposed an anatomical prior-guided PET image reconstruction method based on diffusion models, inspired by the deep diffusion image prior (DDIP) framework. The proposed method alternated between diffusion sampling and model fine-tuning guided by the PET sinogram, enabling the reconstruction of high-quality images from various PET tracers using a score function pretrained on a dataset of another tracer. To improve computational efficiency, the half-quadratic splitting (HQS) algorithm was adopted to decouple network optimization from iterative PET reconstruction. The proposed method was evaluated using one simulation and two clinical datasets. For the simulation study, a model pretrained on [$^{18}$F]FDG data was tested on amyloid-negative PET data to assess out-of-distribution (OOD) performance. For the clinical-data validation, ten low-dose [$^{18}$F]FDG datasets and one [$^{18}$F]Florbetapir dataset were tested on a model pretrained on data from another tracer. Experiment results show that the proposed PET reconstruction method can generalize robustly across tracer distributions and scanner types, providing an efficient and versatile reconstruction framework for low-dose PET imaging.

Magnetic Resonance Imaging (MRI) enables the acquisition of multiple image contrasts, such as T1-weighted (T1w) and T2-weighted (T2w) scans, each offering distinct diagnostic insights. However, acquiring all desired modalities increases scan time and cost, motivating research into computational methods for cross-modal synthesis. To address this, recent approaches aim to synthesize missing MRI contrasts from those already acquired, reducing acquisition time while preserving diagnostic quality. Image-to-image (I2I) translation provides a promising framework for this task. In this paper, we present a comprehensive benchmark of generative models$\unicode{x2013}$specifically, Generative Adversarial Networks (GANs), diffusion models, and flow matching (FM) techniques$\unicode{x2013}$for T1w-to-T2w 2D MRI I2I translation. All frameworks are implemented with comparable settings and evaluated on three publicly available MRI datasets of healthy adults. Our quantitative and qualitative analyses show that the GAN-based Pix2Pix model outperforms diffusion and FM-based methods in terms of structural fidelity, image quality, and computational efficiency. Consistent with existing literature, these results suggest that flow-based models are prone to overfitting on small datasets and simpler tasks, and may require more data to match or surpass GAN performance. These findings offer practical guidance for deploying I2I translation techniques in real-world MRI workflows and highlight promising directions for future research in cross-modal medical image synthesis. Code and models are publicly available at https://github.com/AndreaMoschetto/medical-I2I-benchmark.

The prevalence of Alzheimer's disease and other dementias is increasing as populations live longer lifespans. Imaging is becoming a key component of the workup for patients with cognitive impairment or dementia. Integrated PET-MRI provides a unique opportunity for same-session multimodal characterization with many practical benefits to patients, referring physicians, radiologists, and researchers. The impact of integrated PET-MRI on clinical practice for early adopters of this technology can be profound. Classic imaging findings with integrated PET-MRI are illustrated for common neurodegenerative diseases or clinical-radiological syndromes. This review summarizes recent technical innovations that are being introduced into PET-MRI clinical practice and research for neurodegenerative disease. More recent MRI-based attenuation correction now performs similarly compared to PET-CT (e.g., whole-brain bias < 0.5%) such that early concerns for accurate PET tracer quantification with integrated PET-MRI appear resolved. Head motion is common in this patient population. MRI- and PET data-driven motion correction appear ready for routine use and should substantially improve PET-MRI image quality. PET-MRI by definition eliminates ~50% of the radiation from CT. Multiple hardware and software techniques for improving image quality with lower counts are reviewed (including motion correction). These methods can lower radiation to patients (and staff), increase scanner throughput, and generate better temporal resolution for dynamic PET. Deep learning has been broadly applied to PET-MRI. Deep learning analysis of PET and MRI data may provide accurate classification of different stages of Alzheimer's disease or predict progression to dementia. Over the past 5 years, clinical imaging of neurodegenerative disease has changed due to imaging research and the introduction of anti-amyloid immunotherapy-integrated PET-MRI is best suited for imaging these patients and its use appears poised for rapid growth outside academic medical centers. Evidence level: 5. Technical efficacy: Stage 3.

Mild Cognitive Impairment (MCI) serves as a prodromal stage of Alzheimer's Disease (AD), where early identification and intervention can effectively slow the progression to dementia. However, diagnosing AD remains a significant challenge in neurology due to the confounders caused mainly by the selection bias of multimodal data and the complex relationships between variables. To address these issues, we propose a novel visual-language causal intervention framework named Alzheimer's Disease Prediction with Cross-modal Causal Intervention (ADPC) for diagnostic assistance. Our ADPC employs large language model (LLM) to summarize clinical data under strict templates, maintaining structured text outputs even with incomplete or unevenly distributed datasets. The ADPC model utilizes Magnetic Resonance Imaging (MRI), functional MRI (fMRI) images and textual data generated by LLM to classify participants into Cognitively Normal (CN), MCI, and AD categories. Because of the presence of confounders, such as neuroimaging artifacts and age-related biomarkers, non-causal models are likely to capture spurious input-output correlations, generating less reliable results. Our framework implicitly eliminates confounders through causal intervention. Experimental results demonstrate the outstanding performance of our method in distinguishing CN/MCI/AD cases, achieving state-of-the-art (SOTA) metrics across most evaluation metrics. The study showcases the potential of integrating causal reasoning with multi-modal learning for neurological disease diagnosis.

Hemodynamic analysis is essential for predicting aneurysm rupture and guiding treatment. While magnetic resonance flow imaging enables time-resolved volumetric blood velocity measurements, its low spatiotemporal resolution and signal-to-noise ratio limit its diagnostic utility. To address this, we propose the Localized Fourier Neural Operator (LoFNO), a novel 3D architecture that enhances both spatial and temporal resolution with the ability to predict wall shear stress (WSS) directly from clinical imaging data. LoFNO integrates Laplacian eigenvectors as geometric priors for improved structural awareness on irregular, unseen geometries and employs an Enhanced Deep Super-Resolution Network (EDSR) layer for robust upsampling. By combining geometric priors with neural operator frameworks, LoFNO de-noises and spatiotemporally upsamples flow data, achieving superior velocity and WSS predictions compared to interpolation and alternative deep learning methods, enabling more precise cerebrovascular diagnostics.

The skull is highly durable and plays a significant role in sex determination as one of the most dimorphic bones. The facial canal (FC), a clinically significant canal within the temporal bone, houses the facial nerve. This study aims to estimate sex using morphometric measurements from the FC through machine learning (ML) and artificial neural networks (ANNs). The study utilized Computed Tomography (CT) images of 200 individuals (100 females, 100 males) aged 19-65 years. These images were retrospectively retrieved from the Picture Archiving and Communication Systems (PACS) at Düzce University Faculty of Medicine, Department of Radiology, covering 2021-2024. Bilateral measurements of nine temporal bone parameters were performed in axial, coronal, and sagittal planes. ML algorithms including Quadratic Discriminant Analysis (QDA), Linear Discriminant Analysis (LDA), Decision Tree (DT), Extra Tree Classifier (ETC), Random Forest (RF), Logistic Regression (LR), Gaussian Naive Bayes (GaussianNB), and k-Nearest Neighbors (k-NN) were used, alongside a multilayer perceptron classifier (MLPC) from ANN algorithms. Except for QDA (Acc 0.93), all algorithms achieved an accuracy rate of 0.97. SHapley Additive exPlanations (SHAP) analysis revealed the five most impactful parameters: right SGAs, left SGAs, right TSWs, left TSWs and, the inner mouth width of the left FN, respectively. FN-centered morphometric measurements show high accuracy in sex determination and may aid in understanding FN positioning across sexes and populations. These findings may support rapid and reliable sex estimation in forensic investigations-especially in cases with fragmented craniofacial remains-and provide auxiliary diagnostic data for preoperative planning in otologic and skull base surgeries. They are thus relevant for surgeons, anthropologists, and forensic experts. Not applicable.

Ultra-high resolution 7 tesla (7T) magnetic resonance imaging (MRI) provides detailed anatomical views, offering better signal-to-noise ratio, resolution and tissue contrast than 3T MRI, though at the cost of accessibility. We present an advanced deep learning model for synthesizing 7T brain MRI from 3T brain MRI. Paired 7T and 3T T1-weighted images were acquired from 172 participants (124 cognitively unimpaired, 48 impaired) from the Swedish BioFINDER-2 study. To synthesize 7T MRI from 3T images, we trained two models: a specialized U-Net, and a U-Net integrated with a generative adversarial network (GAN U-Net). Our models outperformed two additional state-of-the-art 3T-to-7T models in image-based evaluation metrics. Four blinded MRI professionals judged our synthetic 7T images as comparable in detail to real 7T images, and superior in subjective visual quality to 7T images, apparently due to the reduction of artifacts. Importantly, automated segmentations of the amygdalae of synthetic GAN U-Net 7T images were more similar to manually segmented amygdalae (n=20), than automated segmentations from the 3T images that were used to synthesize the 7T images. Finally, synthetic 7T images showed similar performance to real 3T images in downstream prediction of cognitive status using MRI derivatives (n=3,168). In all, we show that synthetic T1-weighted brain images approaching 7T quality can be generated from 3T images, which may improve image quality and segmentation, without compromising performance in downstream tasks. Future directions, possible clinical use cases, and limitations are discussed.

Hematoma expansion (HE), including intraventricular hemorrhage (IVH) growth, significantly affects outcomes in patients with intracerebral hemorrhage (ICH). This study aimed to develop, validate, and interpret a deep learning model, HENet, for predicting three definitions of HE. Using CT scans and clinical data from 718 ICH patients across three hospitals, the multicenter retrospective study focused on revised hematoma expansion (RHE) definitions 1 and 2, and conventional HE (CHE). HENet's performance was compared with 2D models and physician predictions using two external validation sets. Results showed that HENet achieved high AUC values for RHE1, RHE2, and CHE predictions, surpassing physicians' predictions and 2D models in net reclassification index and integrated discrimination index for RHE1 and RHE2 outcomes. The Grad-CAM technique provided visual insights into the model's decision-making process. These findings suggest that integrating HENet into clinical practice could improve prediction accuracy and patient outcomes in ICH cases.