Alzheimer disease and related dementias (ADRD) are complex disorders with overlapping symptoms and pathologies. Comprehensive records of symptoms in electronic health records (EHRs) are critical for not only reaching an accurate diagnosis but also supporting ongoing research studies and clinical trials. However, these symptoms are frequently obscured within unstructured clinical notes in EHRs, making manual extraction both time-consuming and labor-intensive. We aimed to automate symptom extraction from the clinical notes of patients with ADRD using fine-tuned large language models (LLMs), compare its performance to regular expression-based symptom recognition, and validate the results using brain magnetic resonance imaging (MRI) data. We fine-tuned LLMs to extract ADRD symptoms across the following 7 domains: memory, executive function, motor, language, visuospatial, neuropsychiatric, and sleep. We assessed the algorithm's performance by calculating the area under the receiver operating characteristic curve (AUROC) for each domain. The extracted symptoms were then validated in two analyses: (1) predicting ADRD diagnosis using the counts of extracted symptoms and (2) examining the association between ADRD symptoms and MRI-derived brain volumes. Symptom extraction across the 7 domains achieved high accuracy with AUROCs ranging from 0.97 to 0.99. Using the counts of extracted symptoms to predict ADRD diagnosis yielded an AUROC of 0.83 (95% CI 0.77-0.89). Symptom associations with brain volumes revealed that a smaller hippocampal volume was linked to memory impairments (odds ratio 0.62, 95% CI 0.46-0.84; P=.006), and reduced pallidum size was associated with motor impairments (odds ratio 0.73, 95% CI 0.58-0.90; P=.04). These results highlight the accuracy and reliability of our high-throughput ADRD phenotyping algorithm. By enabling automated symptom extraction, our approach has the potential to assist with differential diagnosis, as well as facilitate clinical trials and research studies of dementia.

The ability to predict the spreading of pathology in patients with frontotemporal dementia (FTD) is crucial for early diagnosis and targeted interventions. In this study, we examined the relationship between network vulnerability and longitudinal progression of atrophy in FTD patients, using the network diffusion model (NDM) of the spread of pathology. Thirty behavioural variant FTD (bvFTD), 13 semantic variant primary progressive aphasia (svPPA), 14 non-fluent variant primary progressive aphasia (nfvPPA) and 12 semantic behavioural variant FTD (sbvFTD) patients underwent longitudinal T1-weighted MRI. Fifty young controls (20-31 years of age) underwent multi-shell diffusion MRI scan. An NDM was developed to model progression of FTD pathology as a spreading process from a seed through the healthy structural connectome, using connectivity measures from fractional anisotropy and intracellular volume fraction in young controls. Four disease epicentres were initially identified from the peaks of atrophy of each FTD variant: left insula (bvFTD), left temporal pole (svPPA), right temporal pole (sbvFTD) and left supplementary motor area (nfvPPA). Pearson's correlations were calculated between NDM-predicted atrophy in young controls and the observed longitudinal atrophy in FTD patients over a follow-up period of 24 months. The NDM was then run for all 220 brain seeds to verify whether the four epicentres were among those that yielded the highest correlation. Using the NDM, predictive maps in young controls showed progression of pathology from the peaks of atrophy in svPPA, nfvPPA and sbvFTD over 24 months. svPPA exhibited early involvement of the left temporal and occipital lobes, progressing to extensive left hemisphere impairment. nfvPPA and sbvFTD spread in a similar manner bilaterally to frontal, sensorimotor and temporal regions, with sbvFTD additionally affecting the right hemisphere. Moreover, the NDM-predicted atrophy of each region was positively correlated with longitudinal real atrophy, with a greater effect in svPPA and sbvFTD. In bvFTD, the model starting from the left insula (the peak of atrophy) demonstrated a highly left-lateralized pattern, with pathology spreading to frontal, sensorimotor, temporal and basal ganglia regions, with minimal extension to the contralateral hemisphere by 24 months. However, unlike the atrophy peaks observed in the other three phenotypes, the left insula did not show the strongest correlation between the estimated and real atrophy. Instead, the bilateral superior frontal gyrus emerged as optimal seeds for modelling atrophy spread, showing the highest correlation ranking in both hemispheres. Overall, NDM applied on the intracellular volume fraction connectome yielded higher correlations relative to NDM applied on fractional anisotropy maps. The NDM implementation using the cross-sectional structural connectome is a valuable tool to predict patterns of atrophy and spreading of pathology in FTD clinical variants.

The incidence of Alzheimer's disease is rising with the increasing elderly population worldwide. While no cure exists, early diagnosis can significantly slow disease progression. Computer-aided diagnostic systems are becoming critical tools for assisting in the early detection of Alzheimer's disease. In this systematic review, we aim to evaluate recent advancements in computer-aided decision support systems for Alzheimer's disease diagnosis, focusing on data modalities, machine learning methods, and performance metrics. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published between 2021 and 2024 were retrieved from PubMed, IEEEXplore and Web of Science, using search terms related to Alzheimer's disease classification, neuroimaging, machine learning, and diagnostic performance. A total of 39 studies met the inclusion criteria, focusing on the use of Magnetic Resonance Imaging, Positron Emission Tomography, and biomarkers for Alzheimer's disease classification using machine learning models. Multimodal approaches, combining Magnetic Resonance Imaging with Positron Emission Tomography and Cognitive assessments, outperformed single-modality studies in diagnostic accuracy reliability. Convolutional Neural Networks were the most commonly used machine learning models, followed by hybrid models and Random Forest. The highest accuracy reported for binary classification was 100%, while multi-class classification achieved up to 99.98%. Techniques like Synthetic Minority Over-sampling Technique and data augmentation were frequently employed to address data imbalance, improving model generalizability. Our review highlights the advantages of using multimodal data in computer-aided decision support systems for more accurate Alzheimer's disease diagnosis. However, we also identified several limitations, including data imbalance, small sample sizes, and the lack of external validation in most studies. Future research should utilize larger, more diverse datasets, incorporate longitudinal data, and validate models in real-world clinical trials. Additionally, there is a growing need for explainability in machine learning models to ensure they are interpretable and trusted in clinical settings. While computer-aided decision support systems show great promise in improving the early diagnosis of Alzheimer's disease, further work is needed to enhance their robustness, generalizability, and clinical applicability. By addressing these challenges, computer-aided decision support systems could play a pivotal role in the early detection and management of Alzheimer's disease, potentially improving patient outcomes and reducing healthcare costs.

One in ten children experiences sleep-disordered breathing (SDB). Untreated SDB is associated with poor cognition, but the underlying mechanisms are less understood. We assessed the relationship between magnetic resonance imaging (MRI)-derived upper airway volume and children's cognition and regional cortical gray matter volumes. We used five-year data from the Adolescent Brain Cognitive Development study (n=11,875 children, 9-10 years at baseline). Upper airway volumes were derived using a deep learning model applied to 5,552,640 brain MRI slices. The primary outcome was the Total Cognition Composite score from the National Institutes of Health Toolbox (NIH-TB). Secondary outcomes included other NIH-TB measures and cortical gray matter volumes. The habitual snoring group had significantly smaller airway volumes than non-snorers (mean difference=1.2 cm³; 95% CI, 1.0-1.4 cm³; P<0.001). Deep learning-derived airway volume predicted the Total Cognition Composite score (estimated mean difference=3.68 points; 95% CI, 2.41-4.96; P<0.001) per one-unit increase in the natural log of airway volume (~2.7-fold raw volume increase). This airway volume increase was also associated with an average 0.02 cm³ increase in right temporal pole volume (95% CI, 0.01-0.02 cm³; P<0.001). Similar airway volume predicted most NIH-TB domain scores and multiple frontal and temporal gray matter volumes. These brain volumes mediated the relationship between airway volume and cognition. We demonstrate a novel application of deep learning-based airway segmentation in a large pediatric cohort. Upper airway volume is a potential biomarker for cognitive outcomes in pediatric SDB, offers insights into neurobiological mechanisms, and informs future studies on risk stratification. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Glioblastoma is among the most aggressive brain tumors in adults, characterized by patient-specific invasion patterns driven by the underlying brain microstructure. In this work, we present a proof-of-concept for a mathematical model of GBL growth, enabling real-time prediction and patient-specific parameter identification from longitudinal neuroimaging data. The framework exploits a diffuse-interface mathematical model to describe the tumor evolution and a reduced-order modeling strategy, relying on proper orthogonal decomposition, trained on synthetic data derived from patient-specific brain anatomies reconstructed from magnetic resonance imaging and diffusion tensor imaging. A neural network surrogate learns the inverse mapping from tumor evolution to model parameters, achieving significant computational speed-up while preserving high accuracy. To ensure robustness and interpretability, we perform both global and local sensitivity analyses, identifying the key biophysical parameters governing tumor dynamics and assessing the stability of the inverse problem solution. These results establish a methodological foundation for future clinical deployment of patient-specific digital twins in neuro-oncology.

Sodium neuroimaging provides unique insights into the cellular and metabolic properties of brain tumors. However, at 3T, sodium neuroimaging MRI's low signal-to-noise ratio (SNR) and resolution discourages routine clinical use. We evaluated the recently developed Anatomically constrained GAN using physics-based synthetic MRI artifacts" (ATHENA) for high-resolution sodium neuroimaging of brain tumors at 3T. We hypothesized the model would improve the image quality while preserving the inherent sodium information. 4,573 proton MRI scans from 1,390 suspected brain tumor patients were used for training. Sodium and proton MRI datasets from Twenty glioma patients were collected for validation. Twenty-four image-guided biopsies from seven patients were available for sodium-proton exchanger (NHE1) expression evaluation on immunohistochemistry. High-resolution synthetic sodium images were generated using the ATHENA model, then compared to native sodium MRI and NHE1 protein expression from image-guided biopsy samples. The ATHENA produced synthetic-sodium MR with significantly improved SNR (native SNR 18.20 ± 7.04; synthetic SNR 23.83 ± 9.33, P = 0.0079). The synthetic-sodium values were consistent with the native measurements (P = 0.2058), with a strong linear correlation within contrast-enhancing areas of the tumor (R² = 0.7565, P = 0.0005), T2-hyperintense (R² = 0.7325, P < 0.0001), and necrotic areas (R² = 0.7678, P < 0.0001). The synthetic-sodium MR and the relative NHE1 expression from image-guided biopsies were better correlated for the synthetic (ρ = 0.3269, P < 0.0001) than the native (ρ = 0.1732, P = 0.0276) with higher sodium signal in samples expressing elevated NHE1 (P < 0.0001). ATHENA generates high-resolution synthetic-sodium MRI at 3T, enabling clinically attainable multinuclear imaging for brain tumors that retain the inherent information from the native sodium. The resulting synthetic sodium significantly correlates with tissue expression, potentially supporting its utility as a non-invasive marker of underlying sodium homeostasis in brain tumors.

The location of the hemorrhagic of spontaneous intracerebral hemorrhage (sICH) is clinically pivotal for both identifying its etiology and prognosis, but comprehensive and quantitative modeling approach has yet to be thoroughly explored. We employed lesion-symptom mapping to extract the location features of sICH. We registered patients' non-contrast computed tomography image and hematoma masks with standard human brain templates to identify specific affected brain regions. Then, we generated hemorrhage probabilistic maps of different etiologies and prognoses. By integrating radiomics and clinical features into multiple logistic regression models, we developed and validated optimal etiological and prognostic models across three centers, comprising 1162 sICH patients. Hematomas of different etiology have unique spatial distributions. The location-based features demonstrated robust classification of the etiology of spontaneous intracerebral hemorrhage (sICH), with a mean area under the curve (AUC) of 0.825 across diverse datasets. These features provided significant incremental value when integrated into predictive models (fusion model mean AUC = 0.915), outperforming models relying solely on clinical features (mean AUC = 0.828). In prognostic assessments, both hematoma location (mean AUC = 0.762) and radiomic features (mean AUC = 0.837) contributed substantial incremental predictive value, as evidenced by the fusion model's mean AUC of 0.873, compared to models utilizing clinical features alone (mean AUC = 0.771). Our results show that location features were more intrinsically robust, generalizable relative, strong interpretability to the complex modeling of radiomics, our approach demonstrated a novel interpretable, streamlined, comprehensive etiologic classification and prognostic prediction framework for sICH.

INTRODUCTION: 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, variability in tracer types, and challenges in multimodal integration. METHODS: 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. The pipeline is implemented as a web-based platform, requiring no local computational infrastructure or specialized software knowledge. RESULTS: petBrain provides reliable and rapid biomarker quantification, with results comparable to existing pipelines for A and T2. It shows strong concordance with data processed in ADNI databases. The staging and quantification of A/T2/N by petBrain demonstrated good agreement with CSF/plasma biomarkers, clinical status, and cognitive performance. DISCUSSION: petBrain represents a powerful and openly accessible platform for standardized AD biomarker analysis, facilitating applications in clinical research.

Ultra-high-resolution (UHR) photon-counting-detector (PCD) CT improves image resolution but increases noise, necessitating the use of smoother reconstruction kernels that reduce resolution below the 0.125-mm maximum spatial resolution. A denoising convolutional neural network (CNN) was developed to reduce noise in images reconstructed with the available sharpest reconstruction kernel while preserving resolution for enhanced temporal bone visualization to address this issue. With institutional review board approval, the CNN was trained on 6 patient cases of clinical temporal bone imaging (1885 images) and tested on 20 independent cases using a dual-source PCD-CT (NAEOTOM Alpha). Images were reconstructed using quantum iterative reconstruction at strength 3 (QIR3) with both a clinical routine kernel (Hr84) and the sharpest available head kernel (Hr96). The CNN was applied to images reconstructed with Hr96 and QIR1 kernel. For each case, three series of images (Hr84-QIR3, Hr96-QIR3, and Hr96-CNN) were randomized for review by 2 neuroradiologists assessing the overall quality and delineating the modiolus, stapes footplate, and incudomallear joint. The CNN reduced noise by 80% compared with Hr96-QIR3 and by 50% relative to Hr84-QIR3, while maintaining high resolution. Compared with the conventional method at the same kernel (Hr96-QIR3), Hr96-CNN significantly decreased image noise (from 204.63 to 47.35 HU) and improved its structural similarity index (from 0.72 to 0.99). Hr96-CNN images ranked higher than Hr84-QIR3 and Hr96-QIR3 in overall quality (<i>P</i> < .001). Readers preferred Hr96-CNN for all 3 structures. The proposed CNN significantly reduced image noise in UHR PCD-CT, enabling the use of the sharpest kernel. This combination greatly enhanced diagnostic image quality and anatomic visualization.

Multiparametric Magnetic Resonance Imaging (mpMRI) is the gold standard for diagnosing brain tumors, especially gliomas, which are difficult to segment due to their heterogeneity and varied sub-regions. While manual segmentation is time-consuming and error-prone, Deep Learning (DL) automates the process with greater accuracy and speed. We conducted ablation studies on surveyed articles to evaluate the impact of "add-on" modules-addressing challenges like spatial information loss, class imbalance, and overfitting-on glioma segmentation performance. Advanced modules-such as atrous (dilated) convolutions, inception, attention, transformer, and hybrid modules-significantly enhance segmentation accuracy, efficiency, multiscale feature extraction, and boundary delineation, while lightweight modules reduce computational complexity. Experiments on the Brain Tumor Segmentation (BraTS) dataset (comprising low- and high-grade gliomas) confirm their robustness, with top-performing models achieving high Dice score for tumor sub-regions. This survey underscores the need for optimal module selection and placement to balance speed, accuracy, and interpretability in glioma segmentation. Future work should focus on improving model interpretability, lowering computational costs, and boosting generalizability. Tools like NeuroQuant® and Raidionics demonstrate potential for clinical translation. Further refinement could enable regulatory approval, advancing precision in brain tumor diagnosis and treatment planning.