BackgroundAcute appendicitis remains a challenging diagnosis in pediatric populations, with high rates of misdiagnosis and negative appendectomies despite advances in imaging modalities. Current diagnostic tools, including clinical scoring systems like Alvarado and Pediatric Appendicitis Score (PAS), lack sufficient sensitivity and specificity, while reliance on CT scans raises concerns about radiation exposure, contrast hazards and sedation in children. Moreover, no established tool effectively predicts progression from uncomplicated to complicated appendicitis, creating a critical gap in clinical decision-making. ObjectiveTo develop and evaluate a machine learning model that integrates clinical, laboratory, and radiological findings for accurate diagnosis and complication prediction in pediatric appendicitis and to deploy this model as an interpretable web-based tool for clinical decision support. MethodsWe analyzed data from 780 pediatric patients (ages 0-18) with suspected appendicitis admitted to Childrens Hospital St. Hedwig, Regensburg, between 2016 and 2021. For severity prediction, our dataset was augmented with 430 additional cases from published literature and only the confirmed cases of acute appendicitis(n=602) were used. After feature selection using statistical methods and recursive feature elimination, we developed a Random Forest model named Dharma, optimized through hyperparameter tuning and cross-validation. Model performance was evaluated on independent test sets and compared with conventional diagnostic tools. ResultsDharma demonstrated superior diagnostic performance with an AUC-ROC of 0.96 ({+/-}0.02 SD) in cross-validation and 0.97-0.98 on independent test sets. At an optimal threshold of 64%, the model achieved specificity of 88%-98%, sensitivity of 89%-95%, and positive predictive value of 93%-99%. For complication prediction, Dharma attained a sensitivity of 93% ({+/-}0.05 SD) in cross-validation and 96% on the test set, with a negative predictive value of 98%. The model maintained strong performance even in cases where the appendix could not be visualized on ultrasonography (AUC-ROC 0.95, sensitivity 89%, specificity 87% at the threshold of 30%). ConclusionDharma is a novel, interpretable machine learning based clinical decision support tool designed to address the diagnostic challenges of pediatric appendicitis by integrating easily obtainable clinical, laboratory, and radiological data into a unified, real-time predictive framework. Unlike traditional scoring systems and imaging modalities, which may lack specificity or raise safety concerns in children, Dharma demonstrates high accuracy in diagnosing appendicitis and predicting progression from uncomplicated to complicated cases, potentially reducing unnecessary surgeries and CT scans. Its robust performance, even with incomplete imaging data, underscores its utility in resource-limited settings. Delivered through an intuitive, transparent, and interpretable web application, Dharma supports frontline providers--particularly in low- and middle-income settings--in making timely, evidence-based decisions, streamlining patient referrals, and improving clinical outcomes. By bridging critical gaps in current diagnostic and prognostic tools, Dharma offers a practical and accessible 21st-century solution tailored to real-world pediatric surgical care across diverse healthcare contexts. Furthermore, the underlying framework and concepts of Dharma may be adaptable to other clinical challenges beyond pediatric appendicitis, providing a foundation for broader applications of machine learning in healthcare. Author SummaryAccurate diagnosis of pediatric appendicitis remains challenging, with current clinical scores and imaging tests limited by sensitivity, specificity, predictive values, and safety concerns. We developed Dharma, an interpretable machine learning model that integrates clinical, laboratory, and radiological data to assist in diagnosing appendicitis and predicting its severity in children. Evaluated on a large dataset supplemented by published cases, Dharma demonstrated strong diagnostic and prognostic performance, including in cases with incomplete imaging--making it potentially especially useful in resource-limited settings for early decision-making and streamlined referrals. Available as a web-based tool, it provides real-time support to healthcare providers in making evidence-based decisions that could reduce negative appendectomies while avoiding hazards associated with advanced imaging modalities such as sedation, contrast, or radiation exposure. Furthermore, the open-access concepts and framework underlying Dharma have the potential to address diverse healthcare challenges beyond pediatric appendicitis.

This study presents a deep learning system for breast cancer detection in mammography, developed using a modified EfficientNetV2 architecture with enhanced attention mechanisms. The model was trained on mammograms from a major Thai medical center and validated on three distinct datasets: an in-domain test set (9,421 cases), a biopsy-confirmed set (883 cases), and an out-of-domain generalizability set (761 cases) collected from two different hospitals. For cancer detection, the model achieved AUROCs of 0.89, 0.96, and 0.94 on the respective datasets. The system's lesion localization capability, evaluated using metrics including Lesion Localization Fraction (LLF) and Non-Lesion Localization Fraction (NLF), demonstrated robust performance in identifying suspicious regions. Clinical validation through concordance tests showed strong agreement with radiologists: 83.5% classification and 84.0% localization concordance for biopsy-confirmed cases, and 78.1% classification and 79.6% localization concordance for out-of-domain cases. Expert radiologists' acceptance rate also averaged 96.7% for biopsy-confirmed cases, and 89.3% for out-of-domain cases. The system achieved a System Usability Scale score of 74.17 for source hospital, and 69.20 for validation hospitals, indicating good clinical acceptance. These results demonstrate the model's effectiveness in assisting mammogram interpretation, with the potential to enhance breast cancer screening workflows in clinical practice.

In medical image analysis, feature engineering plays an important role in the design and performance of machine learning models. Persistent homology (PH), from the field of topological data analysis (TDA), demonstrates robustness and stability to data perturbations and addresses the limitation from traditional feature extraction approaches where a small change in input results in a large change in feature representation. Using PH, we store persistent topological and geometrical features in the form of the persistence barcode whereby large bars represent global topological features and small bars encapsulate geometrical information of the data. When multiple barcodes are computed from 2D or 3D medical images, two approaches can be used to construct the final topological feature vector in each dimension: aggregating persistence barcodes followed by featurization or concatenating topological feature vectors derived from each barcode. In this study, we conduct a comprehensive analysis across diverse medical imaging datasets to compare the effects of the two aforementioned approaches on the performance of classification models. The results of this analysis indicate that feature concatenation preserves detailed topological information from individual barcodes, yields better classification performance and is therefore a preferred approach when conducting similar experiments.

Dynamic Photoacoustic Computed Tomography (PACT) is an important imaging technique for monitoring physiological processes, capable of providing high-contrast images of optical absorption at much greater depths than traditional optical imaging methods. However, practical instrumentation and geometric constraints limit the number of acoustic sensors available around the imaging target, leading to sparsity in sensor data. Traditional photoacoustic (PA) image reconstruction methods, when directly applied to sparse PA data, produce severe artifacts. Additionally, these traditional methods do not consider the inter-frame relationships in dynamic imaging. Temporal resolution is crucial for dynamic photoacoustic imaging, which is fundamentally limited by the low repetition rate (e.g., 20 Hz) and high cost of high-power laser technology. Recently, Implicit Neural Representation (INR) has emerged as a powerful deep learning tool for solving inverse problems with sparse data, by characterizing signal properties as continuous functions of their coordinates in an unsupervised manner. In this work, we propose an INR-based method to improve dynamic photoacoustic image reconstruction from sparse-views and enhance temporal resolution, using only spatiotemporal coordinates as input. Specifically, the proposed INR represents dynamic photoacoustic images as implicit functions and encodes them into a neural network. The weights of the network are learned solely from the acquired sparse sensor data, without the need for external training datasets or prior images. Benefiting from the strong implicit continuity regularization provided by INR, as well as explicit regularization for low-rank and sparsity, our proposed method outperforms traditional reconstruction methods under two different sparsity conditions, effectively suppressing artifacts and ensuring image quality.

Fragile X Syndrome (FXS) is a rare neurodevelopmental disorder caused by a trinucleotide repeat expansion on the 5 untranslated region of the FMR1 gene. FXS is characterized by intellectual disability, anxiety, sensory hypersensitivity, and difficulties with executive function. A recent phase 2 placebo-controlled clinical trial assessing BPN14770, a first-in-class phosphodiesterase 4D allosteric inhibitor, in 30 adult males (age 18-41 years) with FXS demonstrated cognitive improvements on the NIH Toolbox Cognitive Battery in domains related to language and caregiver reports of improvement in both daily functioning and language. However, individual physiological measures from electroencephalography (EEG) demonstrated only marginal significance for trial efficacy. A secondary analysis of resting state EEG data collected as part of the phase 2 clinical trial evaluating BPN14770 was conducted using a machine learning classification algorithm to classify trial conditions (i.e., baseline, drug, placebo) via linear EEG variable combinations. The algorithm identified a composite of peak alpha frequencies (PAF) across multiple brain regions as a potential biomarker demonstrating BPN14770 efficacy. Increased PAF from baseline was associated with drug but not placebo. Given the relationship between PAF and cognitive function among typically developed adults and those with intellectual disability, as well as previously reported reductions in alpha frequency and power in FXS, PAF represents a potential physiological measure of BPN14770 efficacy.

The integration of artificial intelligence (AI) with radiology signifies a transformative era in medicine. Vision foundation models have been adopted to enhance radiologic imaging analysis. However, the inherent complexities of 2D and 3D radiologic data present unique challenges that existing models, which are typically pretrained on general nonmedical images, do not adequately address. To bridge this gap and harness the diagnostic precision required in radiologic imaging, we introduce radiologic contrastive language-image pretraining (RadCLIP): a cross-modal vision-language foundational model that utilizes a vision-language pretraining (VLP) framework to improve radiologic image analysis. Building on the contrastive language-image pretraining (CLIP) approach, RadCLIP incorporates a slice pooling mechanism designed for volumetric image analysis and is pretrained using a large, diverse dataset of radiologic image-text pairs. This pretraining effectively aligns radiologic images with their corresponding text annotations, resulting in a robust vision backbone for radiologic imaging. Extensive experiments demonstrate RadCLIP's superior performance in both unimodal radiologic image classification and cross-modal image-text matching, underscoring its significant promise for enhancing diagnostic accuracy and efficiency in clinical settings. Our key contributions include curating a large dataset featuring diverse radiologic 2D/3D image-text pairs, pretraining RadCLIP as a vision-language foundation model on this dataset, developing a slice pooling adapter with an attention mechanism for integrating 2D images, and conducting comprehensive evaluations of RadCLIP on various radiologic downstream tasks.

Dynamic magnetic resonance imaging (MRI) plays an indispensable role in cardiac diagnosis. To enable fast imaging, the k-space data can be undersampled but the image reconstruction poses a great challenge of high-dimensional processing. This challenge necessitates extensive training data in deep learning reconstruction methods. In this work, we propose a novel and efficient approach, leveraging a dimension-reduced separable learning scheme that can perform exceptionally well even with highly limited training data. We design this new approach by incorporating spatiotemporal priors into the development of a Deep Separable Spatiotemporal Learning network (DeepSSL), which unrolls an iteration process of a 2D spatiotemporal reconstruction model with both temporal lowrankness and spatial sparsity. Intermediate outputs can also be visualized to provide insights into the network behavior and enhance interpretability. Extensive results on cardiac cine datasets demonstrate that the proposed DeepSSL surpasses stateof-the-art methods both visually and quantitatively, while reducing the demand for training cases by up to 75%. Additionally, its preliminary adaptability to unseen cardiac patients has been verified through a blind reader study conducted by experienced radiologists and cardiologists. Furthermore, DeepSSL enhances the accuracy of the downstream task of cardiac segmentation and exhibits robustness in prospectively undersampled real-time cardiac MRI. DeepSSL is efficient under highly limited training data and adaptive to patients and prospective undersampling. This approach holds promise in addressing the escalating demand for high-dimensional data reconstruction in MRI applications.

Chemical Exchange Saturation Transfer (CEST) MRI has demonstrated its remarkable ability to enhance the detection of macromolecules and metabolites with low concentrations. While CEST mapping is essential for quantifying molecular information, conventional methods face critical limitations: model-based approaches are constrained by limited sensitivity and robustness depending heavily on parameter setups, while data-driven deep learning methods lack generalizability across heterogeneous datasets and acquisition protocols. To overcome these challenges, we propose a Lorentzian-model Informed Neural Representation (LINR) framework for high-quality CEST mapping. LINR employs a self-supervised neural architecture embedding the Lorentzian equation - the fundamental biophysical model of CEST signal evolution - to directly reconstruct high-sensitivity parameter maps from raw z-spectra, eliminating dependency on labeled training data. Convergence of the self-supervised training strategy is guaranteed theoretically, ensuring LINR's mathematical validity. The superior performance of LINR in capturing CEST contrasts is revealed through comprehensive evaluations based on synthetic phantoms and in-vivo experiments (including tumor and Alzheimer's disease models). The intuitive parameter-free design enables adaptive integration into diverse CEST imaging workflows, positioning LINR as a versatile tool for non-invasive molecular diagnostics and pathophysiological discovery.

Pancreatic cancer is a highly aggressive malignancy with rising incidence and mortality rates, often diagnosed at advanced stages. Conventional imaging methods, such as computed tomography (CT) and magnetic resonance imaging (MRI), struggle to assess tumor characteristics and vascular involvement, which are crucial for treatment planning. This paper explores the potential of diffusion magnetic resonance imaging (dMRI) in enhancing pancreatic cancer diagnosis and treatment. Diffusion-based techniques, such as diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI), combined with emerging AI‑powered analysis, provide insights into tissue microstructure, allowing for earlier detection and improved evaluation of tumor cellularity. These methods may help assess prognosis and monitor therapy response by tracking diffusion and perfusion metrics. However, challenges remain, such as standardized protocols and robust data analysis pipelines. Ongoing research, including deep learning applications, aims to improve reliability, and dMRI shows promise in providing functional insights and improving patient outcomes. Further clinical validation is necessary to maximize its benefits.

Advancements in magnetic resonance imaging (MRI) analysis over the past decades have significantly reshaped the field of neuroradiology. The ability to extract multiple quantitative measures from each MRI scan, alongside the development of extensive data repositories, has been fundamental to the emergence of advanced methodologies such as radiomics and artificial intelligence (AI). This educational review aims to delineate the importance of image analysis, highlight key paradigm shifts, examine their implications, and identify existing constraints that must be addressed to facilitate integration into clinical practice. Particular attention is given to aiding junior neuroradiologists in navigating this complex and evolving landscape. A comprehensive review of the available analysis toolboxes was conducted, focusing on major technological advancements in MRI analysis, the evolution of data repositories, and the rise of AI and radiomics in neuroradiology. Stakeholders within the field were identified and their roles examined. Additionally, current challenges and barriers to clinical implementation were analyzed. The analysis revealed several pivotal shifts, including the transition from qualitative to quantitative imaging, the central role of large datasets in developing AI tools, and the growing importance of interdisciplinary collaboration. Key stakeholders-including academic institutions, industry partners, regulatory bodies, and clinical practitioners-were identified, each playing a distinct role in advancing the field. However, significant barriers remain, particularly regarding standardization, data sharing, regulatory approval, and integration into clinical workflows. While advancements in MRI analysis offer tremendous potential to enhance neuroradiology practice, realizing this potential requires overcoming technical, regulatory, and practical barriers. Education and structured support for junior neuroradiologists are essential to ensure they are well-equipped to participate in and drive future developments. A coordinated effort among stakeholders is crucial to facilitate the seamless translation of these technological innovations into everyday clinical practice.