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A Patient-Specific Digital Twin for Adaptive Radiotherapy of Non-Small Cell Lung Cancer
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Radiotherapy continues to become more precise and data dense, with current treatment regimens generating high frequency imaging and dosimetry streams ideally suited for AI driven temporal modeling to characterize how normal tissues evolve with time. Each fraction in biologically guided radiotherapy(BGRT) treated non small cell lung cancer (NSCLC) patients records new metabolic, anatomical, and dose information. However, clinical decision making is largely informed by static, population based NTCP models which overlook the dynamic, unique biological trajectories encoded in sequential data. We developed COMPASS (Comprehensive Personalized Assessment System) for safe radiotherapy, functioning as a temporal digital twin architecture utilizing per fraction PET, CT, dosiomics, radiomics, and cumulative biologically equivalent dose (BED) kinetics to model normal tissue biology as a dynamic time series process. A GRU autoencoder was employed to learn organ specific latent trajectories, which were classified via logistic regression to predict eventual CTCAE grade 1 or higher toxicity. Eight NSCLC patients undergoing BGRT contributed to the 99 organ fraction observations covering 24 organ trajectories (spinal cord, heart, and esophagus). Despite the small cohort, intensive temporal phenotyping allowed for comprehensive analysis of individual dose response dynamics. Our findings revealed a viable AI driven early warning window, as increasing risk ratings occurred from several fractions before clinical toxicity. The dense BED driven representation revealed biologically relevant spatial dose texture characteristics that occur before toxicity and are averaged out with traditional volume based dosimetry. COMPASS establishes a proof of concept for AI enabled adaptive radiotherapy, where treatment is guided by a continually updated digital twin that tracks each patients evolving biological response.
MamaDino: A Hybrid Vision Model for Breast Cancer 3-Year Risk Prediction
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Breast cancer screening programmes increasingly seek to move from one-size-fits-all interval to risk-adapted and personalized strategies. Deep learning (DL) has enabled image-based risk models with stronger 1- to 5-year prediction than traditional clinical models, but leading systems (e.g., Mirai) typically use convolutional backbones, very high-resolution inputs (>1M pixels) and simple multi-view fusion, with limited explicit modelling of contralateral asymmetry. We hypothesised that combining complementary inductive biases (convolutional and transformer-based) with explicit contralateral asymmetry modelling would allow us to match state-of-the-art 3-year risk prediction performance even when operating on substantially lower-resolution mammograms, indicating that using less detailed images in a more structured way can recover state-of-the-art accuracy. We present MamaDino, a mammography-aware multi-view attentional DINO model. MamaDino fuses frozen self-supervised DINOv3 ViT-S features with a trainable CNN encoder at 512x512 resolution, and aggregates bilateral breast information via a BilateralMixer to output a 3-year breast cancer risk score. We train on 53,883 women from OPTIMAM (UK) and evaluate on matched 3-year case-control cohorts: an in-distribution test set from four screening sites and an external out-of-distribution cohort from an unseen site. At breast-level, MamaDino matches Mirai on both internal and external tests while using ~13x fewer input pixels. Adding the BilateralMixer improves discrimination to AUC 0.736 (vs 0.713) in-distribution and 0.677 (vs 0.666) out-of-distribution, with consistent performance across age, ethnicity, scanner, tumour type and grade. These findings demonstrate that explicit contralateral modelling and complementary inductive biases enable predictions that match Mirai, despite operating on substantially lower-resolution mammograms.
ALMo: Interactive Aim-Limit-Defined, Multi-Objective System for Personalized High-Dose-Rate Brachytherapy Treatment Planning and Visualization for Cervical Cancer
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In complex clinical decision-making, clinicians must often track a variety of competing metrics defined by aim (ideal) and limit (strict) thresholds. Sifting through these high-dimensional tradeoffs to infer the optimal patient-specific strategy is cognitively demanding and historically prone to variability. In this paper, we address this challenge within the context of High-Dose-Rate (HDR) brachytherapy for cervical cancer, where planning requires strictly managing radiation hot spots while balancing tumor coverage against organ sparing. We present ALMo (Aim-Limit-defined Multi-Objective system), an interactive decision support system designed to infer and operationalize clinician intent. ALMo employs a novel optimization framework that minimizes manual input through automated parameter setup and enables flexible control over toxicity risks. Crucially, the system allows clinicians to navigate the Pareto surface of dosimetric tradeoffs by directly manipulating intuitive aim and limit values. In a retrospective evaluation of 25 clinical cases, ALMo generated treatment plans that consistently met or exceeded manual planning quality, with 65% of cases demonstrating dosimetric improvements. Furthermore, the system significantly enhanced efficiency, reducing average planning time to approximately 17 minutes, compared to the conventional 30-60 minutes. While validated in brachytherapy, ALMo demonstrates a generalized framework for streamlining interaction in multi-criteria clinical decision-making.
Attention-gated U-Net model for semantic segmentation of brain tumors and feature extraction for survival prognosis
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Gliomas, among the most common primary brain tumors, vary widely in aggressiveness, prognosis, and histology, making treatment challenging due to complex and time-intensive surgical interventions. This study presents an Attention-Gated Recurrent Residual U-Net (R2U-Net) based Triplanar (2.5D) model for improved brain tumor segmentation. The proposed model enhances feature representation and segmentation accuracy by integrating residual, recurrent, and triplanar architectures while maintaining computational efficiency, potentially aiding in better treatment planning. The proposed method achieves a Dice Similarity Score (DSC) of 0.900 for Whole Tumor (WT) segmentation on the BraTS2021 validation set, demonstrating performance comparable to leading models. Additionally, the triplanar network extracts 64 features per planar model for survival days prediction, which are reduced to 28 using an Artificial Neural Network (ANN). This approach achieves an accuracy of 45.71%, a Mean Squared Error (MSE) of 108,318.128, and a Spearman Rank Correlation Coefficient (SRC) of 0.338 on the test dataset.
Thinking Like a Radiologist: A Dataset for Anatomy-Guided Interleaved Vision Language Reasoning in Chest X-ray Interpretation
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Radiological diagnosis is a perceptual process in which careful visual inspection and language reasoning are repeatedly interleaved. Most medical large vision language models (LVLMs) perform visual inspection only once and then rely on text-only chain-of-thought (CoT) reasoning, which operates purely in the linguistic space and is prone to hallucination. Recent methods attempt to mitigate this issue by introducing visually related coordinates, such as bounding boxes. However, these remain a pseudo-visual solution: coordinates are still text and fail to preserve rich visual details like texture and density. Motivated by the interleaved nature of radiological diagnosis, we introduce MMRad-IVL-22K, the first large-scale dataset designed for natively interleaved visual language reasoning in chest X-ray interpretation. MMRad-IVL-22K reflects a repeated cycle of reasoning and visual inspection workflow of radiologists, in which visual rationales complement textual descriptions and ground each step of the reasoning process. MMRad-IVL-22K comprises 21,994 diagnostic traces, enabling systematic scanning across 35 anatomical regions. Experimental results on advanced closed-source LVLMs demonstrate that report generation guided by multimodal CoT significantly outperforms that guided by text-only CoT in clinical accuracy and report quality (e.g., 6\% increase in the RadGraph metric), confirming that high-fidelity interleaved vision language evidence is a non-substitutable component of reliable medical AI. Furthermore, benchmarking across seven state-of-the-art open-source LVLMs demonstrates that models fine-tuned on MMRad-IVL-22K achieve superior reasoning consistency and report quality compared with both general-purpose and medical-specific LVLMs. The project page is available at https://github.com/qiuzyc/thinking_like_a_radiologist.
Lung nodule classification on CT scan patches using 3D convolutional neural networks
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Lung cancer remains one of the most common and deadliest forms of cancer worldwide. The likelihood of successful treatment depends strongly on the stage at which the disease is diagnosed. Therefore, early detection of lung cancer represents a critical medical challenge. However, this task poses significant difficulties for thoracic radiologists due to the large number of studies to review, the presence of multiple nodules within the lungs, and the small size of many nodules, which complicates visual assessment. Consequently, the development of automated systems that incorporate highly accurate and computationally efficient lung nodule detection and classification modules is essential. This study introduces three methodological improvements for lung nodule classification: (1) an advanced CT scan cropping strategy that focuses the model on the target nodule while reducing computational cost; (2) target filtering techniques for removing noisy labels; (3) novel augmentation methods to improve model robustness. The integration of these techniques enables the development of a robust classification subsystem within a comprehensive Clinical Decision Support System for lung cancer detection, capable of operating across diverse acquisition protocols, scanner types, and upstream models (segmentation or detection). The multiclass model achieved a Macro ROC AUC of 0.9176 and a Macro F1-score of 0.7658, while the binary model reached a Binary ROC AUC of 0.9383 and a Binary F1-score of 0.8668 on the LIDC-IDRI dataset. These results outperform several previously reported approaches and demonstrate state-of-the-art performance for this task.
Layer-Specific Fine-Tuning for Improved Negation Handling in Medical Vision-Language Models
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Negation is a fundamental linguistic operation in clinical reporting, yet vision-language models (VLMs) frequently fail to distinguish affirmative from negated medical statements. To systematically characterize this limitation, we introduce a radiology-specific diagnostic benchmark that evaluates polarity sensitivity under controlled clinical conditions, revealing that common medical VLMs consistently confuse negated and non-negated findings. To enable learning beyond simple condition absence, we further construct a contextual clinical negation dataset that encodes structured claims and supports attribute-level negations involving location and severity. Building on these resources, we propose Negation-Aware Selective Training (NAST), an interpretability-guided adaptation method that uses causal tracing effects (CTEs) to modulate layer-wise gradient updates during fine-tuning. Rather than applying uniform learning rates, NAST scales each layer's update according to its causal contribution to negation processing, transforming mechanistic interpretability signals into a principled optimization rule. Experiments demonstrate improved discrimination of affirmative and negated clinical statements without degrading general vision-language alignment, highlighting the value of causal interpretability for targeted model adaptation in safety-critical medical settings. Code and resources are available at https://github.com/healthylaife/NAST.
Prototype-driven fusion of pathology and spatial transcriptomics for interpretable survival prediction
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Whole slide images (WSIs) enable weakly supervised prognostic modeling via multiple instance learning (MIL). Spatial transcriptomics (ST) preserves in situ gene expression, providing a spatial molecular context that complements morphology. As paired WSI-ST cohorts scale to population level, leveraging their complementary spatial signals for prognosis becomes crucial; however, principled cross-modal fusion strategies remain limited for this paradigm. To this end, we introduce PathoSpatial, an interpretable end-to-end framework integrating co-registered WSIs and ST to learn spatially informed prognostic representations. PathoSpatial uses task-guided prototype learning within a multi-level experts architecture, adaptively orchestrating unsupervised within-modality discovery with supervised cross-modal aggregation. By design, PathoSpatial substantially strengthens interpretability while maintaining discriminative ability. We evaluate PathoSpatial on a triple-negative breast cancer cohort with paired ST and WSIs. PathoSpatial delivers strong and consistent performance across five survival endpoints, achieving superior or comparable performance to leading unimodal and multimodal methods. PathoSpatial inherently enables post-hoc prototype interpretation and molecular risk decomposition, providing quantitative, biologically grounded explanations, highlighting candidate prognostic factors. We present PathoSpatial as a proof-of-concept for scalable and interpretable multimodal learning for spatial omics-pathology fusion.
Brain Tumor Classifiers Under Attack: Robustness of ResNet Variants Against Transferable FGSM and PGD Attacks
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Adversarial robustness in deep learning models for brain tumor classification remains an underexplored yet critical challenge, particularly for clinical deployment scenarios involving MRI data. In this work, we investigate the susceptibility and resilience of several ResNet-based architectures, referred to as BrainNet, BrainNeXt and DilationNet, against gradient-based adversarial attacks, namely FGSM and PGD. These models, based on ResNet, ResNeXt, and dilated ResNet variants respectively, are evaluated across three preprocessing configurations (i) full-sized augmented, (ii) shrunk augmented and (iii) shrunk non-augmented MRI datasets. Our experiments reveal that BrainNeXt models exhibit the highest robustness to black-box attacks, likely due to their increased cardinality, though they produce weaker transferable adversarial samples. In contrast, BrainNet and Dilation models are more vulnerable to attacks from each other, especially under PGD with higher iteration steps and $α$ values. Notably, shrunk and non-augmented data significantly reduce model resilience, even when the untampered test accuracy remains high, highlighting a key trade-off between input resolution and adversarial vulnerability. These results underscore the importance of jointly evaluating classification performance and adversarial robustness for reliable real-world deployment in brain MRI analysis.
Locally Interpretable Individualized Treatment Rules for Black-Box Decision Models
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Individualized treatment rules (ITRs) aim to optimize healthcare by tailoring treatment decisions to patient-specific characteristics. Existing methods typically rely on either interpretable but inflexible models or highly flexible black-box approaches that sacrifice interpretability; moreover, most impose a single global decision rule across patients. We introduce the Locally Interpretable Individualized Treatment Rule (LI-ITR) method, which combines flexible machine learning models to accurately learn complex treatment outcomes with locally interpretable approximations to construct subject-specific treatment rules. LI-ITR employs variational autoencoders to generate realistic local synthetic samples and learns individualized decision rules through a mixture of interpretable experts. Simulation studies show that LI-ITR accurately recovers true subject-specific local coefficients and optimal treatment strategies. An application to precision side-effect management in breast cancer illustrates the necessity of flexible predictive modeling and highlights the practical utility of LI-ITR in estimating optimal treatment rules while providing transparent, clinically interpretable explanations.