Joseph Jacob

Ashkan Pakzad, Mou-Cheng Xu, Wing Keung Cheung et al.

Several chronic lung diseases, like idiopathic pulmonary fibrosis (IPF) are characterised by abnormal dilatation of the airways. Quantification of airway features on computed tomography (CT) can help characterise disease progression. Physics based airway measurement algorithms have been developed, but have met with limited success in part due to the sheer diversity of airway morphology seen in clinical practice. Supervised learning methods are also not feasible due to the high cost of obtaining precise airway annotations. We propose synthesising airways by style transfer using perceptual losses to train our model, Airway Transfer Network (ATN). We compare our ATN model with a state-of-the-art GAN-based network (simGAN) using a) qualitative assessment; b) assessment of the ability of ATN and simGAN based CT airway metrics to predict mortality in a population of 113 patients with IPF. ATN was shown to be quicker and easier to train than simGAN. ATN-based airway measurements were also found to be consistently stronger predictors of mortality than simGAN-derived airway metrics on IPF CTs. Airway synthesis by a transformation network that refines synthetic data using perceptual losses is a realistic alternative to GAN-based methods for clinical CT analyses of idiopathic pulmonary fibrosis. Our source code can be found at https://github.com/ashkanpakzad/ATN that is compatible with the existing open-source airway analysis framework, AirQuant.

Yaozhi Lu, Shahab Aslani, An Zhao et al.

In this study, we present a hybrid CNN-RNN approach to investigate long-term survival of subjects in a lung cancer screening study. Subjects who died of cardiovascular and respiratory causes were identified whereby the CNN model was used to capture imaging features in the CT scans and the RNN model was used to investigate time series and thus global information. The models were trained on subjects who underwent cardiovascular and respiratory deaths and a control cohort matched to participant age, gender, and smoking history. The combined model can achieve an AUC of 0.76 which outperforms humans at cardiovascular mortality prediction. The corresponding F1 and Matthews Correlation Coefficient are 0.63 and 0.42 respectively. The generalisability of the model is further validated on an 'external' cohort. The same models were applied to survival analysis with the Cox Proportional Hazard model. It was demonstrated that incorporating the follow-up history can lead to improvement in survival prediction. The Cox neural network can achieve an IPCW C-index of 0.75 on the internal dataset and 0.69 on an external dataset. Delineating imaging features associated with long-term survival can help focus preventative interventions appropriately, particularly for under-recognised pathologies thereby potentially reducing patient morbidity.

Wing Keung Cheung, Ashkan Pakzad, Nesrin Mogulkoc et al.

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.

Wing Keung Cheung, Jeremy Kalindjian, Robert Bell et al.

Early detection and diagnosis of coronary artery disease (CAD) could save lives and reduce healthcare costs. The current clinical practice is to perform CAD diagnosis through analysing medical images from computed tomography coronary angiography (CTCA). Most current approaches utilise deep learning methods but require centerline extraction and multi-planar reconstruction. These indirect methods are not designed in a clinician-friendly manner, and they complicate the interventional procedure. Furthermore, the current deep learning methods do not provide exact explainability and limit the usefulness of these methods to be deployed in clinical settings. In this study, we first propose a 3D Resnet-50 deep learning model to directly classify normal subjects and CAD patients on CTCA images, then we demonstrate a 2D modified U-Net model can be subsequently employed to segment the coronary arteries. Our proposed approach outperforms the state-of-the-art models by 21.43% in terms of classification accuracy. The classification model with focal loss provides a better and more focused heat map, and the segmentation model provides better explainability than the classification-only model. The proposed holistic approach not only provides a simpler and clinician-friendly solution but also good classification accuracy and exact explainability for CAD diagnosis.

Mou-Cheng Xu, Yu-Kun Zhou, Chen Jin et al.

We propose MisMatch, a novel consistency-driven semi-supervised segmentation framework which produces predictions that are invariant to learnt feature perturbations. MisMatch consists of an encoder and a two-head decoders. One decoder learns positive attention to the foreground regions of interest (RoI) on unlabelled images thereby generating dilated features. The other decoder learns negative attention to the foreground on the same unlabelled images thereby generating eroded features. We then apply a consistency regularisation on the paired predictions. MisMatch outperforms state-of-the-art semi-supervised methods on a CT-based pulmonary vessel segmentation task and a MRI-based brain tumour segmentation task. In addition, we show that the effectiveness of MisMatch comes from better model calibration than its supervised learning counterpart.

Mou-Cheng Xu, Yukun Zhou, Chen Jin et al.

This paper concerns pseudo labelling in segmentation. Our contribution is fourfold. Firstly, we present a new formulation of pseudo-labelling as an Expectation-Maximization (EM) algorithm for clear statistical interpretation. Secondly, we propose a semi-supervised medical image segmentation method purely based on the original pseudo labelling, namely SegPL. We demonstrate SegPL is a competitive approach against state-of-the-art consistency regularisation based methods on semi-supervised segmentation on a 2D multi-class MRI brain tumour segmentation task and a 3D binary CT lung vessel segmentation task. The simplicity of SegPL allows less computational cost comparing to prior methods. Thirdly, we demonstrate that the effectiveness of SegPL may originate from its robustness against out-of-distribution noises and adversarial attacks. Lastly, under the EM framework, we introduce a probabilistic generalisation of SegPL via variational inference, which learns a dynamic threshold for pseudo labelling during the training. We show that SegPL with variational inference can perform uncertainty estimation on par with the gold-standard method Deep Ensemble.

Shahab Aslani, Watjana Lilaonitkul, Vaishnavi Gnanananthan et al.

During the COVID-19 pandemic, the sheer volume of imaging performed in an emergency setting for COVID-19 diagnosis has resulted in a wide variability of clinical CXR acquisitions. This variation is seen in the CXR projections used, image annotations added and in the inspiratory effort and degree of rotation of clinical images. The image analysis community has attempted to ease the burden on overstretched radiology departments during the pandemic by developing automated COVID-19 diagnostic algorithms, the input for which has been CXR imaging. Large publicly available CXR datasets have been leveraged to improve deep learning algorithms for COVID-19 diagnosis. Yet the variable quality of clinically-acquired CXRs within publicly available datasets could have a profound effect on algorithm performance. COVID-19 diagnosis may be inferred by an algorithm from non-anatomical features on an image such as image labels. These imaging shortcuts may be dataset-specific and limit the generalisability of AI systems. Understanding and correcting key potential biases in CXR images is therefore an essential first step prior to CXR image analysis. In this study, we propose a simple and effective step-wise approach to pre-processing a COVID-19 chest X-ray dataset to remove undesired biases. We perform ablation studies to show the impact of each individual step. The results suggest that using our proposed pipeline could increase accuracy of the baseline COVID-19 detection algorithm by up to 13%.

Ahmed H. Shahin, Joseph Jacob, Daniel C. Alexander et al.

Idiopathic Pulmonary Fibrosis (IPF) is an inexorably progressive fibrotic lung disease with a variable and unpredictable rate of progression. CT scans of the lungs inform clinical assessment of IPF patients and contain pertinent information related to disease progression. In this work, we propose a multi-modal method that uses neural networks and memory banks to predict the survival of IPF patients using clinical and imaging data. The majority of clinical IPF patient records have missing data (e.g. missing lung function tests). To this end, we propose a probabilistic model that captures the dependencies between the observed clinical variables and imputes missing ones. This principled approach to missing data imputation can be naturally combined with a deep survival analysis model. We show that the proposed framework yields significantly better survival analysis results than baselines in terms of concordance index and integrated Brier score. Our work also provides insights into novel image-based biomarkers that are linked to mortality.

Shahab Aslani, Mehran Azimbagirad, Daryl Cheng et al.

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.

Niccolò McConnell, Pardeep Vasudev, Daisuke Yamada et al.

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.

Ahmed H. Shahin, An Zhao, Alexander C. Whitehead et al.

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.

Moucheng Xu, Yukun Zhou, Chen Jin et al.

In this paper, we study pseudo-labelling. Pseudo-labelling employs raw inferences on unlabelled data as pseudo-labels for self-training. We elucidate the empirical successes of pseudo-labelling by establishing a link between this technique and the Expectation Maximisation algorithm. Through this, we realise that the original pseudo-labelling serves as an empirical estimation of its more comprehensive underlying formulation. Following this insight, we present a full generalisation of pseudo-labels under Bayes' theorem, termed Bayesian Pseudo Labels. Subsequently, we introduce a variational approach to generate these Bayesian Pseudo Labels, involving the learning of a threshold to automatically select high-quality pseudo labels. In the remainder of the paper, we showcase the applications of pseudo-labelling and its generalised form, Bayesian Pseudo-Labelling, in the semi-supervised segmentation of medical images. Specifically, we focus 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 whole brain tumours from MRI volumes; and 4) 3D binary segmentation of prostate from MRI volumes. We further demonstrate that pseudo-labels can enhance the robustness of the learned representations. The code is released in the following GitHub repository: https://github.com/moucheng2017/EMSSL

Ashkan Pakzad, Wing Keung Cheung, Kin Quan et al.

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that systematically parcellates the airway tree into its lobes and generational branches from a deep learning based airway segmentation, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent.

Yukun Zhou, Moucheng Xu, Yipeng Hu et al.

Accurate multi-class segmentation is a long-standing challenge in medical imaging, especially in scenarios where classes share strong similarity. Segmenting retinal blood vessels in retinal photographs is one such scenario, in which arteries and veins need to be identified and differentiated from each other and from the background. Intra-segment misclassification, i.e. veins classified as arteries or vice versa, frequently occurs when arteries and veins intersect, whereas in binary retinal vessel segmentation, error rates are much lower. We thus propose a new approach that decomposes multi-class segmentation into multiple binary, followed by a binary-to-multi-class fusion network. The network merges representations of artery, vein, and multi-class feature maps, each of which are supervised by expert vessel annotation in adversarial training. A skip-connection based merging process explicitly maintains class-specific gradients to avoid gradient vanishing in deep layers, to favor the discriminative features. The results show that, our model respectively improves F1-score by 4.4\%, 5.1\%, and 4.2\% compared with three state-of-the-art deep learning based methods on DRIVE-AV, LES-AV, and HRF-AV data sets. Code: https://github.com/rmaphoh/Learning-AVSegmentation

Kin Quan, Ryutaro Tanno, Rebecca J. Shipley et al.

Purpose: This paper proposes a pipeline to acquire a scalar tapering measurement from the carina to the most distal point of an individual airway visible on CT. We show the applicability of using tapering measurements on clinically acquired data by quantifying the reproducibility of the tapering measure. Methods: We generate a spline from the centreline of an airway to measure the area and arclength at contiguous intervals. The tapering measurement is the gradient of the linear regression between area in log space and arclength. The reproducibility of the measure was assessed by analysing different radiation doses, voxel sizes and reconstruction kernel on single timepoint and longitudinal CT scans and by evaluating the effct of airway bifurcations. Results: Using 74 airways from 10 CT scans, we show a statistical difference, p = 3.4 $\times$ 10$^{-4}$ in tapering between healthy airways (n = 35) and those affected by bronchiectasis (n = 39). The difference between the mean of the two populations was 0.011mm$^{-1}$ and the difference between the medians of the two populations was 0.006mm$^{-1}$. The tapering measurement retained a 95\% confidence interval of $\pm$0.005mm$^{-1}$ in a simulated 25 mAs scan and retained a 95% confidence of $\pm$0.005mm$^{-1}$ on simulated CTs up to 1.5 times the original voxel size. Conclusion: We have established an estimate of the precision of the tapering measurement and estimated the effect on precision of simulated voxel size and CT scan dose. We recommend that the scanner calibration be undertaken with the phantoms as described, on the specific CT scanner, radiation dose and reconstruction algorithm that is to be used in any quantitative studies. Our code is available at https://github.com/quan14/AirwayTaperingInCT

Kin Quan, Rebecca J. Shipley, Ryutaro Tanno et al.

Bronchiectasis is the permanent dilation of airways. Patients with the disease can suffer recurrent exacerbations, reducing their quality of life. The gold standard to diagnose and monitor bronchiectasis is accomplished by inspection of chest computed tomography (CT) scans. A clinician examines the broncho-arterial ratio to determine if an airway is brochiectatic. The visual analysis assumes the blood vessel diameter remains constant, although this assumption is disputed in the literature. We propose a simple measurement of tapering along the airways to diagnose and monitor bronchiectasis. To this end, we constructed a pipeline to measure the cross-sectional area along the airways at contiguous intervals, starting from the carina to the most distal point observable. Using a phantom with calibrated 3D printed structures, the precision and accuracy of our algorithm extends to the sub voxel level. The tapering measurement is robust to bifurcations along the airway and was applied to chest CT images acquired in clinical practice. The result is a statistical difference in tapering rate between airways with bronchiectasis and controls. Our code is available at https://github.com/quan14/AirwayTaperingInCT.

Kin Quan, Ryutaro Tanno, Michael Duong et al.

Numerous lung diseases, such as idiopathic pulmonary fibrosis (IPF), exhibit dilation of the airways. Accurate measurement of dilatation enables assessment of the progression of disease. Unfortunately the combination of image noise and airway bifurcations causes high variability in the profiles of cross-sectional areas, rendering the identification of affected regions very difficult. Here we introduce a noise-robust method for automatically detecting the location of progressive airway dilatation given two profiles of the same airway acquired at different time points. We propose a probabilistic model of abrupt relative variations between profiles and perform inference via Reversible Jump Markov Chain Monte Carlo sampling. We demonstrate the efficacy of the proposed method on two datasets; (i) images of healthy airways with simulated dilatation; (ii) pairs of real images of IPF-affected airways acquired at 1 year intervals. Our model is able to detect the starting location of airway dilatation with an accuracy of 2.5mm on simulated data. The experiments on the IPF dataset display reasonable agreement with radiologists. We can compute a relative change in airway volume that may be useful for quantifying IPF disease progression. The code is available at https://github.com/quan14/Modelling_Airway_Geometry_as_Stock_Market_Data

Anja Thieme, Abhijith Rajamohan, Benjamin Cooper et al. · cambridge, microsoft-research

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.

An Zhao, Moucheng Xu, Ahmed H. Shahin et al.

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.

Moucheng Xu, Yukun Zhou, Tobias Goodwin-Allcock et al.

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.

Shahab Aslani, Pavan Alluri, Eyjolfur Gudmundsson et al.

Lung cancer is the leading cause of cancer-related mortality worldwide. Lung cancer screening (LCS) using annual low-dose computed tomography (CT) scanning has been proven to significantly reduce lung cancer mortality by detecting cancerous lung nodules at an earlier stage. Improving risk stratification of malignancy risk in lung nodules can be enhanced using machine/deep learning algorithms. However most existing algorithms: a) have primarily assessed single time-point CT data alone thereby failing to utilize the inherent advantages contained within longitudinal imaging datasets; b) have not integrated into computer models pertinent clinical data that might inform risk prediction; c) have not assessed algorithm performance on the spectrum of nodules that are most challenging for radiologists to interpret and where assistance from analytic tools would be most beneficial. Here we show the performance of our time-series deep learning model (DeepCAD-NLM-L) which integrates multi-model information across three longitudinal data domains: nodule-specific, lung-specific, and clinical demographic data. We compared our time-series deep learning model to a) radiologist performance on CTs from the National Lung Screening Trial enriched with the most challenging nodules for diagnosis; b) a nodule management algorithm from a North London LCS study (SUMMIT). Our model demonstrated comparable and complementary performance to radiologists when interpreting challenging lung nodules and showed improved performance (AUC=88\%) against models utilizing single time-point data only. The results emphasise the importance of time-series, multi-modal analysis when interpreting malignancy risk in LCS.

Mou-Cheng Xu, Yukun Zhou, Chen Jin et al.

Semi-supervised learning (SSL) is a promising machine learning paradigm to address the issue of label scarcity in medical imaging. SSL methods were originally developed in image classification. The state-of-the-art SSL methods in image classification utilise consistency regularisation to learn unlabelled predictions which are invariant to input level perturbations. However, image level perturbations violate the cluster assumption in the setting of segmentation. Moreover, existing image level perturbations are hand-crafted which could be sub-optimal. Therefore, it is a not trivial to straightforwardly adapt existing SSL image classification methods in segmentation. In this paper, we propose MisMatch, a semi-supervised segmentation framework based on the consistency between paired predictions which are derived from two differently learnt morphological feature perturbations. MisMatch consists of an encoder and two decoders. One decoder learns positive attention for foreground on unlabelled data thereby generating dilated features of foreground. The other decoder learns negative attention for foreground on the same unlabelled data thereby generating eroded features of foreground. We first develop a 2D U-net based MisMatch framework and perform extensive cross-validation on a CT-based pulmonary vessel segmentation task and show that MisMatch statistically outperforms state-of-the-art semi-supervised methods when only 6.25\% of the total labels are used. In a second experiment, we show that U-net based MisMatch outperforms state-of-the-art methods on an MRI-based brain tumour segmentation task. In a third experiment, we show that a 3D MisMatch outperforms a previous method using input level augmentations, on a left atrium segmentation task. Lastly, we find that the performance improvement of MisMatch over the baseline might originate from its better calibration.

Le Zhang, Ryutaro Tanno, Mou-Cheng Xu et al.

Recent years have seen increasing use of supervised learning methods for segmentation tasks. However, the predictive performance of these algorithms depends on the quality of labels. This problem is particularly pertinent in the medical image domain, where both the annotation cost and inter-observer variability are high. In a typical label acquisition process, different human experts provide their estimates of the "true" segmentation labels under the influence of their own biases and competence levels. Treating these noisy labels blindly as the ground truth limits the performance that automatic segmentation algorithms can achieve. In this work, we present a method for jointly learning, from purely noisy observations alone, the reliability of individual annotators and the true segmentation label distributions, using two coupled CNNs. The separation of the two is achieved by encouraging the estimated annotators to be maximally unreliable while achieving high fidelity with the noisy training data. We first define a toy segmentation dataset based on MNIST and study the properties of the proposed algorithm. We then demonstrate the utility of the method on three public medical imaging segmentation datasets with simulated (when necessary) and real diverse annotations: 1) MSLSC (multiple-sclerosis lesions); 2) BraTS (brain tumours); 3) LIDC-IDRI (lung abnormalities). In all cases, our method outperforms competing methods and relevant baselines particularly in cases where the number of annotations is small and the amount of disagreement is large. The experiments also show strong ability to capture the complex spatial characteristics of annotators' mistakes.

Mou-Cheng Xu, Neil P. Oxtoby, Daniel C. Alexander et al.

In convolutional neural network based medical image segmentation, the periphery of foreground regions representing malignant tissues may be disproportionately assigned as belonging to the background class of healthy tissues \cite{attenUnet}\cite{AttenUnet2018}\cite{InterSeg}\cite{UnetFrontNeuro}\cite{LearnActiveContour}. This leads to high false negative detection rates. In this paper, we propose a novel attention mechanism to directly address such high false negative rates, called Paying Attention to Mistakes. Our attention mechanism steers the models towards false positive identification, which counters the existing bias towards false negatives. The proposed mechanism has two complementary implementations: (a) "explicit" steering of the model to attend to a larger Effective Receptive Field on the foreground areas; (b) "implicit" steering towards false positives, by attending to a smaller Effective Receptive Field on the background areas. We validated our methods on three tasks: 1) binary dense prediction between vehicles and the background using CityScapes; 2) Enhanced Tumour Core segmentation with multi-modal MRI scans in BRATS2018; 3) segmenting stroke lesions using ultrasound images in ISLES2018. We compared our methods with state-of-the-art attention mechanisms in medical imaging, including self-attention, spatial-attention and spatial-channel mixed attention. Across all of the three different tasks, our models consistently outperform the baseline models in Intersection over Union (IoU) and/or Hausdorff Distance (HD). For instance, in the second task, the "explicit" implementation of our mechanism reduces the HD of the best baseline by more than $26\%$, whilst improving the IoU by more than $3\%$. We believe our proposed attention mechanism can benefit a wide range of medical and computer vision tasks, which suffer from over-detection of background.

Yipeng Hu, Joseph Jacob, Geoffrey JM Parker et al.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2, emerged into a world being rapidly transformed by artificial intelligence (AI) based on big data, computational power and neural networks. The gaze of these networks has in recent years turned increasingly towards applications in healthcare. It was perhaps inevitable that COVID-19, a global disease propagating health and economic devastation, should capture the attention and resources of the world's computer scientists in academia and industry. The potential for AI to support the response to the pandemic has been proposed across a wide range of clinical and societal challenges, including disease forecasting, surveillance and antiviral drug discovery. This is likely to continue as the impact of the pandemic unfolds on the world's people, industries and economy but a surprising observation on the current pandemic has been the limited impact AI has had to date in the management of COVID-19. This correspondence focuses on exploring potential reasons behind the lack of successful adoption of AI models developed for COVID-19 diagnosis and prognosis, in front-line healthcare services. We highlight the moving clinical needs that models have had to address at different stages of the epidemic, and explain the importance of translating models to reflect local healthcare environments. We argue that both basic and applied research are essential to accelerate the potential of AI models, and this is particularly so during a rapidly evolving pandemic. This perspective on the response to COVID-19, may provide a glimpse into how the global scientific community should react to combat future disease outbreaks more effectively.