Association of Progressive PPFE and Mortality in Lung Cancer Screening Cohorts

Background: Pleuroparenchymal fibroelastosis (PPFE) is an upper lobe predominant fibrotic lung abnormality associated with increased mortality in established interstitial lung disease. However, the clinical significance of radiologic PPFE progression in lung cancer screening (LCS) populations remains unclear. Methods: We analysed longitudinal low-dose CT scans and clinical data from two LCS studies: National Lung Screening Trial (NLST; n=7,980); SUMMIT study (n=8,561). An automated algorithm quantified PPFE volume on baseline and follow-up scans. Annualised change in PPFE was derived and dichotomised using a distribution-based threshold to define progressive PPFE. Associations between progressive PPFE and mortality were evaluated using Cox proportional hazards models adjusted for demographic and clinical variables. In SUMMIT cohort, associations between progressive PPFE and clinical outcomes were assessed using incidence rate ratios (IRR) and odds ratios (OR). Findings: Progressive PPFE independently associated with mortality in both LCS cohorts (NLST: Hazard Ratio (HR)=1.25, 95% Confidence Interval (CI): 1.01--1.56, p=0.042; SUMMIT: HR=3.14, 95% CI: 1.66--5.97, p<0.001). Within SUMMIT, progressive PPFE was strongly associated with higher respiratory admissions (IRR=2.79, p<0.001), increased antibiotic and steroid use (IRR=1.55, p=0.010), and showed a trend towards higher modified medical research council scores (OR=1.40, p=0.055). Interpretation: Radiologic PPFE progression independently associates with mortality across two large LCS cohorts, and associates with adverse clinical outcomes. Quantitative assessment of PPFE progression may provide a clinically relevant imaging biomarker to identify individuals at increased risk of respiratory morbidity within LCS programmes.

Association of Radiologic PPFE Change with Mortality in Lung Cancer Screening Cohorts

Background: Pleuroparenchymal fibroelastosis (PPFE) is an upper lobe predominant fibrotic lung abnormality associated with increased mortality in established interstitial lung disease. However, the clinical significance of radiologic PPFE progression in lung cancer screening populations remains unclear. We investigated whether longitudinal change in PPFE quantified on low dose CT independently associates with mortality and respiratory morbidity. Methods: We analysed longitudinal low-dose CT scans and clinical data from two lung cancer screening studies: the National Lung Screening Trial (NLST; n=7980) and the SUMMIT study (n=8561). An automated algorithm quantified PPFE volume on baseline and follow up scans. Annualised change in PPFE (dPPFE) was derived and dichotomised using a distribution based threshold to define progressive PPFE. Associations between dPPFE and mortality were evaluated using Cox proportional hazards models adjusted for demographic and clinical variables. In the SUMMIT cohort, dPPFE was also examined in relation to clinical outcomes. Findings: dPPFE independently associated with mortality in both cohorts (NLST: HR 1.25, 95% CI 1.01-1.56, p=0.042; SUMMIT: HR 3.14, 95% CI 1.66-5.97, p<0.001). Kaplan-Meier curves showed reduced survival among participants with progressive PPFE in both cohorts. In SUMMIT, dPPFE was associated with higher respiratory admissions (IRR 2.79, p<0.001), increased antibiotic and steroid use (IRR 1.55, p=0.010), and a trend towards higher mMRC scores (OR 1.40, p=0.055). Interpretation: Radiologic PPFE progression independently associates with mortality across two large lung cancer screening cohorts and with adverse clinical outcomes. Quantitative assessment of PPFE progression may provide a clinically relevant imaging biomarker for identifying individuals at increased respiratory risk within screening programmes.

A computationally frugal open-source foundation model for thoracic disease detection in lung cancer screening programs

Low-dose computed tomography (LDCT) imaging employed in lung cancer screening (LCS) programs is increasing in uptake worldwide. LCS programs herald a generational opportunity to simultaneously detect cancer and non-cancer-related early-stage lung disease. Yet these efforts are hampered by a shortage of radiologists to interpret scans at scale. Here, we present TANGERINE, a computationally frugal, open-source vision foundation model for volumetric LDCT analysis. Designed for broad accessibility and rapid adaptation, TANGERINE can be fine-tuned off the shelf for a wide range of disease-specific tasks with limited computational resources and training data. Relative to models trained from scratch, TANGERINE demonstrates fast convergence during fine-tuning, thereby requiring significantly fewer GPU hours, and displays strong label efficiency, achieving comparable or superior performance with a fraction of fine-tuning data. Pretrained using self-supervised learning on over 98,000 thoracic LDCTs, including the UK's largest LCS initiative to date and 27 public datasets, TANGERINE achieves state-of-the-art performance across 14 disease classification tasks, including lung cancer and multiple respiratory diseases, while generalising robustly across diverse clinical centres. By extending a masked autoencoder framework to 3D imaging, TANGERINE offers a scalable solution for LDCT analysis, departing from recent closed, resource-intensive models by combining architectural simplicity, public availability, and modest computational requirements. Its accessible, open-source lightweight design lays the foundation for rapid integration into next-generation medical imaging tools that could transform LCS initiatives, allowing them to pivot from a singular focus on lung cancer detection to comprehensive respiratory disease management in high-risk populations.

4D VQ-GAN: Synthesising Medical Scans at Any Time Point for Personalised Disease Progression Modelling of Idiopathic Pulmonary Fibrosis

Understanding the progression trajectories of diseases is crucial for early diagnosis and effective treatment planning. This is especially vital for life-threatening conditions such as Idiopathic Pulmonary Fibrosis (IPF), a chronic, progressive lung disease with a prognosis comparable to many cancers. Computed tomography (CT) imaging has been established as a reliable diagnostic tool for IPF. Accurately predicting future CT scans of early-stage IPF patients can aid in developing better treatment strategies, thereby improving survival outcomes. In this paper, we propose 4D Vector Quantised Generative Adversarial Networks (4D-VQ-GAN), a model capable of generating realistic CT volumes of IPF patients at any time point. The model is trained using a two-stage approach. In the first stage, a 3D-VQ-GAN is trained to reconstruct CT volumes. In the second stage, a Neural Ordinary Differential Equation (ODE) based temporal model is trained to capture the temporal dynamics of the quantised embeddings generated by the encoder in the first stage. We evaluate different configurations of our model for generating longitudinal CT scans and compare the results against ground truth data, both quantitatively and qualitatively. For validation, we conduct survival analysis using imaging biomarkers derived from generated CT scans and achieve a C-index comparable to that of biomarkers derived from the real CT scans. The survival analysis results demonstrate the potential clinical utility inherent to generated longitudinal CT scans, showing that they can reliably predict survival outcomes.

MRI Parameter Mapping via Gaussian Mixture VAE: Breaking the Assumption of Independent Pixels

We introduce and demonstrate a new paradigm for quantitative parameter mapping in MRI. Parameter mapping techniques, such as diffusion MRI and quantitative MRI, have the potential to robustly and repeatably measure biologically-relevant tissue maps that strongly relate to underlying microstructure. Quantitative maps are calculated by fitting a model to multiple images, e.g. with least-squares or machine learning. However, the overwhelming majority of model fitting techniques assume that each voxel is independent, ignoring any co-dependencies in the data. This makes model fitting sensitive to voxelwise measurement noise, hampering reliability and repeatability. We propose a self-supervised deep variational approach that breaks the assumption of independent pixels, leveraging redundancies in the data to effectively perform data-driven regularisation of quantitative maps. We demonstrate that our approach outperforms current model fitting techniques in dMRI simulations and real data. Especially with a Gaussian mixture prior, our model enables sharper quantitative maps, revealing finer anatomical details that are not presented in the baselines. Our approach can hence support the clinical adoption of parameter mapping methods such as dMRI and qMRI.

Challenges for Responsible AI Design and Workflow Integration in Healthcare: A Case Study of Automatic Feeding Tube Qualification in Radiology

Nasogastric tubes (NGTs) are feeding tubes that are inserted through the nose into the stomach to deliver nutrition or medication. If not placed correctly, they can cause serious harm, even death to patients. Recent AI developments demonstrate the feasibility of robustly detecting NGT placement from Chest X-ray images to reduce risks of sub-optimally or critically placed NGTs being missed or delayed in their detection, but gaps remain in clinical practice integration. In this study, we present a human-centered approach to the problem and describe insights derived following contextual inquiry and in-depth interviews with 15 clinical stakeholders. The interviews helped understand challenges in existing workflows, and how best to align technical capabilities with user needs and expectations. We discovered the trade-offs and complexities that need consideration when choosing suitable workflow stages, target users, and design configurations for different AI proposals. We explored how to balance AI benefits and risks for healthcare staff and patients within broader organizational and medical-legal constraints. We also identified data issues related to edge cases and data biases that affect model training and evaluation; how data documentation practices influence data preparation and labelling; and how to measure relevant AI outcomes reliably in future evaluations. We discuss how our work informs design and development of AI applications that are clinically useful, ethical, and acceptable in real-world healthcare services.

CenTime: Event-Conditional Modelling of Censoring in Survival Analysis

Survival analysis is a valuable tool for estimating the time until specific events, such as death or cancer recurrence, based on baseline observations. This is particularly useful in healthcare to prognostically predict clinically important events based on patient data. However, existing approaches often have limitations; some focus only on ranking patients by survivability, neglecting to estimate the actual event time, while others treat the problem as a classification task, ignoring the inherent time-ordered structure of the events. Furthermore, the effective utilization of censored samples - training data points where the exact event time is unknown - is essential for improving the predictive accuracy of the model. In this paper, we introduce CenTime, a novel approach to survival analysis that directly estimates the time to event. Our method features an innovative event-conditional censoring mechanism that performs robustly even when uncensored data is scarce. We demonstrate that our approach forms a consistent estimator for the event model parameters, even in the absence of uncensored data. Furthermore, CenTime is easily integrated with deep learning models with no restrictions on batch size or the number of uncensored samples. We compare our approach with standard survival analysis methods, including the Cox proportional-hazard model and DeepHit. Our results indicate that CenTime offers state-of-the-art performance in predicting time-to-death while maintaining comparable ranking performance. Our implementation is publicly available at https://github.com/ahmedhshahin/CenTime.

A 3D deep learning classifier and its explainability when assessing coronary artery disease

Early detection and diagnosis of coronary artery disease (CAD) could save lives and reduce healthcare costs. In this study, we propose a 3D Resnet-50 deep learning model to directly classify normal subjects and CAD patients on computed tomography coronary angiography images. Our proposed method outperforms a 2D Resnet-50 model by 23.65%. Explainability is also provided by using a Grad-GAM. Furthermore, we link the 3D CAD classification to a 2D two-class semantic segmentation for improved explainability and accurate abnormality localisation.

A data-centric deep learning approach to airway segmentation

The morphology and distribution of airway tree abnormalities enables diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. In this study, we propose a data-centric deep learning technique to segment the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway trees at different scales. In terms of segmentation performance (dice similarity coefficient), our method outperforms the baseline model by 2.5% on average when a combined loss is used. Further, our proposed technique has a low GPU usage and high flexibility enabling it to be deployed on any 2D deep learning model.

Expectation Maximization Pseudo Labelling for Segmentation with Limited Annotations

We study pseudo labelling and its generalisation for semi-supervised segmentation of medical images. Pseudo labelling has achieved great empirical successes in semi-supervised learning, by utilising raw inferences on unlabelled data as pseudo labels for self-training. In our paper, we build a connection between pseudo labelling and the Expectation Maximization algorithm which partially explains its empirical successes. We thereby realise that the original pseudo labelling is an empirical estimation of its underlying full formulation. Following this insight, we demonstrate the full generalisation of pseudo labels under Bayes' principle, called Bayesian Pseudo Labels. We then provide a variational approach to learn to approximate Bayesian Pseudo Labels, by learning a threshold to select good quality pseudo labels. In the rest of the paper, we demonstrate the applications of Pseudo Labelling and its generalisation Bayesian Psuedo Labelling in semi-supervised segmentation of medical images on: 1) 3D binary segmentation of lung vessels from CT volumes; 2) 2D multi class segmentation of brain tumours from MRI volumes; 3) 3D binary segmentation of brain tumours from MRI volumes. We also show that pseudo labels can enhance the robustness of the learnt representations.