In magnetic resonance imaging (MRI), variations in scan parameters and scanner specifications can result in differences in image appearance. To minimize these differences, harmonization in MRI has been suggested as a crucial image processing technique. In this study, we developed an MR physics-based harmonization framework, Physics-Constrained Deep Neural Network for multisite and multiscanner Harmonization (PhyCHarm). PhyCHarm includes two deep neural networks: (1) the Quantitative Maps Generator to generate T₁- and M₀-maps and (2) the Harmonization Network. We used an open dataset consisting of 3T MP2RAGE images from 50 healthy individuals for the Quantitative Maps Generator and a traveling dataset consisting of 3T T₁w images from 9 healthy individuals for the Harmonization Network. PhyCHarm was evaluated using the structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR), and normalized-root-mean square error (NRMSE) for the Quantitative Maps Generator, and using SSIM, PSNR, and volumetric analysis for the Harmonization network, respectively. PhyCHarm demonstrated increased SSIM and PSNR, the highest Dice score in the FSL FAST segmentation results for gray and white matter compared to U-Net, Pix2Pix, CALAMITI, and HarmonizingFlows. PhyCHarm showed a greater reduction in volume differences after harmonization for gray and white matter than U-Net, Pix2Pix, CALAMITI, or HarmonizingFlows. As an initial step toward developing advanced harmonization techniques, we investigated the applicability of physics-based constraints within a supervised training strategy. The proposed physics constraints could be integrated with unsupervised methods, paving the way for more sophisticated harmonization qualities.

This study investigates the use of Vision Transformers (ViTs) to predict Freedom from Local Failure (FFLF) in patients with brain metastases using pre-operative MRI scans. The goal is to develop a model that enhances risk stratification and informs personalized treatment strategies. Within the AURORA retrospective trial, patients (n = 352) who received surgical resection followed by post-operative stereotactic radiotherapy (SRT) were collected from seven hospitals. We trained our ViT for the direct image-to-risk task on T1-CE and FLAIR sequences and combined clinical features along the way. We employed segmentation-guided image modifications, model adaptations, and specialized patient sampling strategies during training. The model was evaluated with five-fold cross-validation and ensemble learning across all validation runs. An external, international test cohort (n = 99) within the dataset was used to assess the generalization capabilities of the model, and saliency maps were generated for explainability analysis. We achieved a competent C-Index score of 0.7982 on the test cohort, surpassing all clinical, CNN-based, and hybrid baselines. Kaplan-Meier analysis showed significant FFLF risk stratification. Saliency maps focusing on the BM core confirmed that model explanations aligned with expert observations. Our ViT-based model offers a potential for personalized treatment strategies and follow-up regimens in patients with brain metastases. It provides an alternative to radiomics as a robust, automated tool for clinical workflows, capable of improving patient outcomes through effective risk assessment and stratification.

Hyperpolarized ¹²⁹Xenon magnetic resonance imaging (MRI) measures the extent of lung ventilation by ventilation defect percent (VDP), but VDP alone cannot distinguish between diseases. Prior studies have reported anecdotal evidence of disease-specific defect patterns such as wedge-shaped defects in asthma and polka-dot defects in lymphangioleiomyomatosis (LAM). Neural network artificial intelligence can evaluate image shapes and textures to classify images, but this has not been attempted in xenon MRI. We hypothesized that an artificial intelligence network trained on ventilation MRI could classify diseases based on spatial patterns in lung MR images alone. Xenon MRI data in six pulmonary conditions (control, asthma, bronchiolitis obliterans syndrome, bronchopulmonary dysplasia, cystic fibrosis, LAM) were used to train convolutional neural networks. Network performance was assessed with top-1 and top-2 accuracy, recall, precision, and one-versus-all area under the curve (AUC). Gradient class-activation-mapping (Grad-CAM) was used to visualize what parts of the images were important for classification. Training/testing data were collected from 262 participants. The top performing network (VGG-16) had top-1 accuracy=56%, top-2 accuracy=78%, recall=.30, precision=.70, and AUC=.85. The network performed better on larger classes (top-1 accuracy: control=62% [n=57], CF=67% [n=85], LAM=69% [n=61]) and outperformed human observers (human top-1 accuracy=40%, network top-1 accuracy=61% on a single training fold). We developed an artificial intelligence tool that could classify disease from xenon ventilation images alone that outperformed human observers. This suggests that xenon images have additional, disease-specific information that could be useful for cases that are clinically challenging or for disease phenotyping.

Early and accurate detection of oral cancer plays a pivotal role in improving patient outcomes. This research introduces a custom-designed, 19-layer convolutional neural network (CNN) for the automated diagnosis of oral cancer using clinical images of the lips and tongue. The methodology integrates advanced preprocessing steps, including min-max normalization and histogram-based contrast enhancement, to optimize image features critical for reliable classification. The model is extensively validated on the publicly available Oral Cancer (Lips and Tongue) Images (OCI) dataset, which is divided into 80% training and 20% testing subsets. Comprehensive performance evaluation employs established metrics-accuracy, sensitivity, specificity, precision, and F1-score. Our CNN architecture achieved an accuracy of 99.54%, sensitivity of 95.73%, specificity of 96.21%, precision of 96.34%, and F1-score of 96.03%, demonstrating substantial improvements over prominent transfer learning benchmarks, including SqueezeNet, AlexNet, Inception, VGG19, and ResNet50, all tested under identical experimental protocols. The model's robust performance, efficient computation, and high reliability underline its practicality for clinical application and support its superiority over existing approaches. This study provides a reproducible pipeline and a new reference point for deep learning-based oral cancer detection, facilitating translation into real-world healthcare environments and promising enhanced diagnostic confidence.

The aim of this study is to validate the effectiveness of an AI tool trained on Indian data in a Dutch medical center and to assess its ability to classify and localize fractures. Conventional radiographs acquired between January 2019 and November 2022 were analyzed using a multitask deep neural network. The tool, trained on Indian data, identified and localized fractures in 17 body parts. The reference standard was based on radiology reports resulting from routine clinical workflow and confirmed by an experienced musculoskeletal radiologist. The analysis included both patient-wise and fracture-wise evaluations, employing binary and Intersection over Union (IoU) metrics to assess fracture detection and localization accuracy. In total, 14,311 radiographs (median age, 48 years (range 18-98), 7265 male) were analyzed and categorized by body parts; clavicle, shoulder, humerus, elbow, forearm, wrist, hand and finger, pelvis, hip, femur, knee, lower leg, ankle, foot and toe. 4156/14,311 (29%) had fractures. The AI tool demonstrated overall patient-wise sensitivity, specificity, and AUC of 87.1% (95% CI: 86.1-88.1%), 87.1% (95% CI: 86.4-87.7%), and 0.92 (95% CI: 0.91-0.93), respectively. Fracture detection rate was 60% overall, ranging from 7% for rib fractures to 90% for clavicle fractures. This study validates a fracture detection AI tool on a Western-European dataset, originally trained on Indian data. While classification performance is robust on real clinical data, fracture-wise analysis reveals variability in localization accuracy, underscoring the need for refinement in fracture localization. AI may provide help by enabling optimal use of limited resources or personnel. This study evaluates an AI tool designed to aid in detecting fractures, possibly reducing reading time or optimization of radiology workflow by prioritizing fracture-positive cases. Cross-validation on a consecutive Dutch cohort confirms this AI tool's clinical robustness. The tool detected fractures with 87% sensitivity, 87% specificity, and 0.92 AUC. AI localizes 60% of fractures, the highest for clavicle (90%) and lowest for ribs (7%).

This study aimed to develop an interpretable, domain-generalizable deep learning model for microvascular invasion (MVI) assessment in hepatocellular carcinoma (HCC). Utilizing a retrospective dataset of 546 HCC patients from five centers, we developed and validated a clinical-radiological model and deep learning models aimed at MVI prediction. The models were developed on a dataset of 263 cases consisting of data from three centers, internally validated on a set of 66 patients, and externally tested on two independent sets. An adversarial network-based deep learning (AD-DL) model was developed to learn domain-invariant features from multiple centers within the training set. The area under the receiver operating characteristic curve (AUC) was calculated using pathological MVI status. With the best-performed model, early recurrence-free survival (ERFS) stratification was validated on the external test set by the log-rank test, and the differentially expressed genes (DEGs) associated with MVI status were tested on the RNA sequencing analysis of the Cancer Imaging Archive. The AD-DL model demonstrated the highest diagnostic performance and generalizability with an AUC of 0.793 in the internal test set, 0.801 in external test set 1, and 0.773 in external test set 2. The model's prediction of MVI status also demonstrated a significant correlation with ERFS (p = 0.048). DEGs associated with MVI status were primarily enriched in the metabolic processes and the Wnt signaling pathway, and the epithelial-mesenchymal transition process. The AD-DL model allows preoperative MVI prediction and ERFS stratification in HCC patients, which has a good generalizability and biological interpretability. The adversarial network-based deep learning model predicts MVI status well in HCC patients and demonstrates good generalizability. By integrating bioinformatics analysis of the model's predictions, it achieves biological interpretability, facilitating its clinical translation. Current MVI assessment models for HCC lack interpretability and generalizability. The adversarial network-based model's performance surpassed clinical radiology and squeeze-and-excitation network-based models. Biological function analysis was employed to enhance the interpretability and clinical translatability of the adversarial network-based model.

Accurately and efficiently identifying mitotic figures (MFs) is crucial for diagnosing and grading various cancers, including glioblastoma (GBM), a highly aggressive brain tumour requiring precise and timely intervention. Traditional manual counting of MFs in whole slide images (WSIs) is labour-intensive and prone to interobserver variability. Our study introduces a deep active learning framework that addresses these challenges with minimal human intervention. We utilized a dataset of GBM WSIs from The Cancer Genome Atlas (TCGA). Our framework integrates convolutional neural networks (CNNs) with an active learning strategy. Initially, a CNN is trained on a small, annotated dataset. The framework then identifies uncertain samples from the unlabelled data pool, which are subsequently reviewed by experts. These ambiguous cases are verified and used for model retraining. This iterative process continues until the model achieves satisfactory performance. Our approach achieved 81.75% precision and 82.48% recall for MF detection. For MF subclass classification, it attained an accuracy of 84.1%. Furthermore, this approach significantly reduced annotation time - approximately 900 min across 66 WSIs - cutting the effort nearly in half compared to traditional methods. Our deep active learning framework demonstrates a substantial improvement in both efficiency and accuracy for MF detection and classification in GBM WSIs. By reducing reliance on large annotated datasets, it minimizes manual effort while maintaining high performance. This methodology can be generalized to other medical imaging tasks, supporting broader applications in the healthcare domain.

PurposeTo quantify spectral-domain optical coherence tomography (SD-OCT) images cross-sectionally and longitudinally in a large cohort of molecularly characterized patients with inherited retinal disease (IRDs) from the UK. DesignRetrospective study of imaging data. ParticipantsPatients with a clinical and molecularly confirmed diagnosis of IRD who have undergone macular SD-OCT imaging at Moorfields Eye Hospital (MEH) between 2011 and 2019. We retrospectively identified 4,240 IRD patients from the MEH database (198 distinct IRD genes), including 69,664 SD-OCT macular volumes. MethodsEight features of interest were defined: retina, fovea, intraretinal cystic spaces (ICS), subretinal fluid (SRF), subretinal hyper-reflective material (SHRM), pigment epithelium detachment (PED), ellipsoid zone loss (EZ-loss) and retinal pigment epithelium loss (RPE-loss). Manual annotations of five b-scans per SD-OCT volume was performed for the retinal features by four graders based on a defined grading protocol. A total of 1,749 b-scans from 360 SD-OCT volumes across 275 patients were annotated for the eight retinal features for training and testing of a neural-network-based segmentation model, AIRDetect-OCT, which was then applied to the entire imaging dataset. Main Outcome MeasuresPerformance of AIRDetect-OCT, comparing to inter-grader agreement was evaluated using Dice score on a held-out dataset. Feature prevalence, volume and area were analysed cross-sectionally and longitudinally. ResultsThe inter-grader Dice score for manual segmentation was [&ge;]90% for retina, ICS, SRF, SHRM and PED, >77% for both EZ-loss and RPE-loss. Model-grader agreement was >80% for segmentation of retina, ICS, SRF, SHRM, and PED, and >68% for both EZ-loss and RPE-loss. Automatic segmentation was applied to 272,168 b-scans across 7,405 SD-OCT volumes from 3,534 patients encompassing 176 unique genes. Accounting for age, male patients exhibited significantly more EZ-loss (19.6mm2 vs 17.9mm2, p<2.8x10-4) and RPE-loss (7.79mm2 vs 6.15mm2, p<3.2x10-6) than females. RPE-loss was significantly higher in Asian patients than other ethnicities (9.37mm2 vs 7.29mm2, p<0.03). ICS average total volume was largest in RS1 (0.47mm3) and NR2E3 (0.25mm3), SRF in BEST1 (0.21mm3) and PED in EFEMP1 (0.34mm3). BEST1 and PROM1 showed significantly different patterns of EZ-loss (p<10-4) and RPE-loss (p<0.02) comparing the dominant to the recessive forms. Sectoral analysis revealed significantly increased EZ-loss in the inferior quadrant compared to superior quadrant for RHO ({Delta}=-0.414 mm2, p=0.036) and EYS ({Delta}=-0.908 mm2, p=1.5x10-4). In ABCA4 retinopathy, more severe genotypes (group A) were associated with faster progression of EZ-loss (2.80{+/-}0.62 mm2/yr), whilst the p.(Gly1961Glu) variant (group D) was associated with slower progression (0.56 {+/-}0.18 mm2/yr). There were also sex differences within groups with males in group A experiencing significantly faster rates of progression of RPE-loss (2.48 {+/-}1.40 mm2/yr vs 0.87 {+/-}0.62 mm2/yr, p=0.047), but lower rates in groups B, C, and D. ConclusionsAIRDetect-OCT, a novel deep learning algorithm, enables large-scale OCT feature quantification in IRD patients uncovering cross-sectional and longitudinal phenotype correlations with demographic and genotypic parameters.

In radiation oncology, precision and timeliness of both planning and treatment are paramount values of patient care. Machine learning has increasingly been applied to various aspects of photon radiotherapy to reduce manual error and improve the efficiency of clinical decision making; however, applications to proton therapy remain an emerging field in comparison. This systematic review aims to comprehensively cover all current and potential applications of machine learning to the proton therapy clinical workflow, an area that has not been extensively explored in literature. PubMed and Embase were utilized to identify studies pertinent to machine learning in proton therapy between 2019 to 2024. An initial search on PubMed was made with the search strategy "'proton therapy', 'machine learning', 'deep learning'". A subsequent search on Embase was made with "("proton therapy") AND ("machine learning" OR "deep learning")". In total, 38 relevant studies have been summarized and incorporated. It is observed that U-Net architectures are prevalent in the patient pre-screening process, while convolutional neural networks play an important role in dose and range prediction. Both image quality improvement and transformation between modalities to decrease extraneous radiation are popular targets of various models. To adaptively improve treatments, advanced architectures such as general deep inception or deep cascaded convolution neural networks improve online dose verification and range monitoring. With the rising clinical usage of proton therapy, machine learning models have been increasingly proposed to facilitate both treatment and discovery. Significantly improving patient screening, planning, image quality, and dose and range calculation, machine learning is advancing the precision and personalization of proton therapy.

Identifying patients with multiple sclerosis (pwMS) at higher risk of clinical progression is essential to inform clinical management. We aimed to build prognostic models using machine learning (ML) algorithms predicting long-term clinical outcomes based on a systematic mapping of volumetric, radiomic, and macrostructural disconnection features from routine brain MRI scans of pwMS. In this longitudinal monocentric study, 3T structural MRI scans of pwMS were retrospectively analyzed. Based on a ten-year clinical follow-up (average duration=9.4±1.1 years), patients were classified according to confirmed disability progression (CDP) and cognitive impairment (CI) as assessed through the Expanded Disability Status Scale (EDSS) and the Brief International Cognitive Assessment of Multiple Sclerosis (BICAMS) battery, respectively. 3D-T1w and FLAIR images were automatically segmented to obtain volumes, disconnection scores (estimated based on lesion masks and normative tractography data), and radiomic features from 116 gray matter regions defined according to the Automated Anatomical Labelling (AAL) atlas. Three ML algorithms (Extra Trees, Logistic Regression, and Support Vector Machine) were used to build models predicting long-term CDP and CI based on MRI-derived features. Feature selection was performed on the training set with a multi-step process, and models were validated with a holdout approach, randomly splitting the patients into training (75%) and test (25%) sets. We studied 177 pwMS (M/F = 51/126; mean±SD age: 35.2±8.7 years). Long-term CDP and CI were observed in 71 and 55 patients, respectively. Regarding the CDP class prediction analysis, the feature selection identified 13-, 12-, and 10-feature subsets obtaining an accuracy on the test set of 0.71, 0.69, and 0.67 for the Extra Trees, Logistic Regression, and Support Vector Machine classifiers, respectively. Similarly, for the CI prediction, subsets of 16, 17, and 19 features were selected, with 0.69, 0.64, and 0.62 accuracy values on the test set, respectively. There were no significant differences in accuracy between ML models for CDP (p=0.65) or CI (p=0.31). Building on quantitative features derived from conventional MRI scans, we obtained long-term prognostic models, potentially informing patients' stratification and clinical decision-making. MS, multiple sclerosis; pwMS, people with MS; HC, healthy controls; ML, machine learning; DD, disease duration; EDSS, Expanded Disability Status Scale; TLV, total lesion volume; CDP, confirmed disability progression; CI, cognitive impairment; BICAMS, Brief International Cognitive Assessment of Multiple Sclerosis.