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Quantitative magnetic resonance imaging (qMRI) is increasingly investigated for use in a variety of clinical tasks from diagnosis, through staging, to treatment monitoring. However, experiment design in qMRI, the identification of the optimal acquisition protocols, has been focused on obtaining the most precise parameter estimations, with no regard for the specific requirements of downstream tasks. Here we propose SCREENER: A general framework for task-specific experiment design in quantitative MRI. SCREENER incorporates a task-specific objective and seeks the optimal protocol with a deep-reinforcement-learning (DRL) based optimization strategy. To illustrate this framework, we employ a task of classifying the inflammation status of bone marrow using diffusion MRI data with intravoxel incoherent motion (IVIM) modelling. Results demonstrate SCREENER outperforms previous ad hoc and optimized protocols under clinical signal-to-noise ratio (SNR) conditions, achieving significant improvement, both in binary classification tasks, e.g. from 67% to 89%, and in a multi-class classification task, from 46% to 59%. Additionally, we show this improvement is robust to the SNR. Lastly, we demonstrate the advantage of DRL-based optimization strategy, enabling zero-shot discovery of near-optimal protocols for a range of SNRs not used in training. In conclusion, SCREENER has the potential to enable wider uptake of qMRI in the clinic.

Prior work on the Image Quality Transfer on Diffusion MRI (dMRI) has shown significant improvement over traditional interpolation methods. However, the difficulty in obtaining ultra-high resolution Diffusion MRI scans poses a problem in training neural networks to obtain high-resolution dMRI scans. Here we hypothesise that the inclusion of structural MRI images, which can be acquired at much higher resolutions, can be used as a guide to obtaining a more accurate high-resolution dMRI output. To test our hypothesis, we have constructed a novel framework that incorporates structural MRI scans together with dMRI to obtain high-resolution dMRI scans. We set up tests which evaluate the validity of our claim through various configurations and compare the performance of our approach against a unimodal approach. Our results show that the inclusion of structural MRI scans do lead to an improvement in high-resolution image prediction when T1w data is incorporated into the model input.

In this work, we introduce Brain Latent Progression (BrLP), a novel spatiotemporal disease progression model based on latent diffusion. BrLP is designed to predict the evolution of diseases at the individual level on 3D brain MRIs. Existing deep generative models developed for this task are primarily data-driven and face challenges in learning disease progressions. BrLP addresses these challenges by incorporating prior knowledge from disease models to enhance the accuracy of predictions. To implement this, we propose to integrate an auxiliary model that infers volumetric changes in various brain regions. Additionally, we introduce Latent Average Stabilization (LAS), a novel technique to improve spatiotemporal consistency of the predicted progression. BrLP is trained and evaluated on a large dataset comprising 11,730 T1-weighted brain MRIs from 2,805 subjects, collected from three publicly available, longitudinal Alzheimer's Disease (AD) studies. In our experiments, we compare the MRI scans generated by BrLP with the actual follow-up MRIs available from the subjects, in both cross-sectional and longitudinal settings. BrLP demonstrates significant improvements over existing methods, with an increase of 22% in volumetric accuracy across AD-related brain regions and 43% in image similarity to the ground-truth scans. The ability of BrLP to generate conditioned 3D scans at the subject level, along with the novelty of integrating prior knowledge to enhance accuracy, represents a significant advancement in disease progression modeling, opening new avenues for precision medicine. The code of BrLP is available at the following link: https://github.com/LemuelPuglisi/BrLP.

Recent developments in diffusion models have advanced conditioned image generation, yet they struggle with reconstructing out-of-distribution (OOD) images, such as unseen tumors in medical images, causing "image hallucination" and risking misdiagnosis. We hypothesize such hallucinations result from local OOD regions in the conditional images. We verify that partitioning the OOD region and conducting separate image generations alleviates hallucinations in several applications. From this, we propose a training-free diffusion framework that reduces hallucination with multiple Local Diffusion processes. Our approach involves OOD estimation followed by two modules: a "branching" module generates locally both within and outside OOD regions, and a "fusion" module integrates these predictions into one. Our evaluation shows our method mitigates hallucination over baseline models quantitatively and qualitatively, reducing misdiagnosis by 40% and 25% in the real-world medical and natural image datasets, respectively. It also demonstrates compatibility with various pre-trained diffusion models.

Recent learning-based approaches have made astonishing advances in calibrated medical imaging like computerized tomography (CT), yet they struggle to generalize in uncalibrated modalities -- notably magnetic resonance (MR) imaging, where performance is highly sensitive to the differences in MR contrast, resolution, and orientation. This prevents broad applicability to diverse real-world clinical protocols. We introduce Brain-ID, an anatomical representation learning model for brain imaging. With the proposed "mild-to-severe" intra-subject generation, Brain-ID is robust to the subject-specific brain anatomy regardless of the appearance of acquired images (e.g., contrast, deformation, resolution, artifacts). Trained entirely on synthetic data, Brain-ID readily adapts to various downstream tasks through only one layer. We present new metrics to validate the intra- and inter-subject robustness of Brain-ID features, and evaluate their performance on four downstream applications, covering contrast-independent (anatomy reconstruction/contrast synthesis, brain segmentation), and contrast-dependent (super-resolution, bias field estimation) tasks. Extensive experiments on six public datasets demonstrate that Brain-ID achieves state-of-the-art performance in all tasks on different MRI modalities and CT, and more importantly, preserves its performance on low-resolution and small datasets. Code is available at https://github.com/peirong26/Brain-ID., Comment: 26 pages, 11 figures

Low-field (LF) MRI scanners (<1T) are still prevalent in settings with limited resources or unreliable power supply. However, they often yield images with lower spatial resolution and contrast than high-field (HF) scanners. This quality disparity can result in inaccurate clinician interpretations. Image Quality Transfer (IQT) has been developed to enhance the quality of images by learning a mapping function between low and high-quality images. Existing IQT models often fail to restore high-frequency features, leading to blurry output. In this paper, we propose a 3D conditional diffusion model to improve 3D volumetric data, specifically LF MR images. Additionally, we incorporate a cross-batch mechanism into the self-attention and padding of our network, ensuring broader contextual awareness even under small 3D patches. Experiments on the publicly available Human Connectome Project (HCP) dataset for IQT and brain parcellation demonstrate that our model outperforms existing methods both quantitatively and qualitatively. The code is publicly available at \url{https://github.com/edshkim98/DiffusionIQT}.

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.

Computational models of neurodegeneration aim to emulate the evolving pattern of pathology in the brain during neurodegenerative disease, such as Alzheimer's disease. Previous studies have made specific choices on the mechanisms of pathology production and diffusion, or assume that all the subjects lie on the same disease progression trajectory. However, the complexity and heterogeneity of neurodegenerative pathology suggests that multiple mechanisms may contribute synergistically with complex interactions, meanwhile the degree of contribution of each mechanism may vary among individuals. We thus put forward a coupled-mechanisms modelling framework which non-linearly combines the network-topology-informed pathology appearance with the process of pathology spreading within a dynamic modelling system. We account for the heterogeneity of disease by fitting the model at the individual level, allowing the epicenters and rate of progression to vary among subjects. We construct a Bayesian model selection framework to account for feature importance and parameter uncertainty. This provides a combination of mechanisms that best explains the observations for each individual from the ADNI dataset. With the obtained distribution of mechanism importance for each subject, we are able to identify subgroups of patients sharing similar combinations of apparent mechanisms., Comment: MICCAI 2023

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.

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.

Purpose: Previous quantitative MR imaging studies using self-supervised deep learning have reported biased parameter estimates at low SNR. Such systematic errors arise from the choice of Mean Squared Error (MSE) loss function for network training, which is incompatible with Rician-distributed MR magnitude signals. To address this issue, we introduce the negative log Rician likelihood (NLR) loss. Methods: A numerically stable and accurate implementation of the NLR loss was developed to estimate quantitative parameters of the apparent diffusion coefficient (ADC) model and intra-voxel incoherent motion (IVIM) model. Parameter estimation accuracy, precision and overall error were evaluated in terms of bias, variance and root mean squared error and compared against the MSE loss over a range of SNRs (5 - 30). Results: Networks trained with NLR loss show higher estimation accuracy than MSE for the ADC and IVIM diffusion coefficients as SNR decreases, with minimal loss of precision or total error. At high effective SNR (high SNR and small diffusion coefficients), both losses show comparable accuracy and precision for all parameters of both models. Conclusion: The proposed NLR loss is numerically stable and accurate across the full range of tested SNRs and improves parameter estimation accuracy of diffusion coefficients using self-supervised deep learning. We expect the development to benefit quantitative MR imaging techniques broadly, enabling more accurate parameter estimation from noisy data., Comment: 16 pages, 6 figures

The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI., Comment: Under review

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, Comment: Accepted in Medical Image Analysis

Low-field (<1T) magnetic resonance imaging (MRI) scanners remain in widespread use in low- and middle-income countries (LMICs) and are commonly used for some applications in higher income countries e.g. for small child patients with obesity, claustrophobia, implants, or tattoos. However, low-field MR images commonly have lower resolution and poorer contrast than images from high field (1.5T, 3T, and above). Here, we present Image Quality Transfer (IQT) to enhance low-field structural MRI by estimating from a low-field image the image we would have obtained from the same subject at high field. Our approach uses (i) a stochastic low-field image simulator as the forward model to capture uncertainty and variation in the contrast of low-field images corresponding to a particular high-field image, and (ii) an anisotropic U-Net variant specifically designed for the IQT inverse problem. We evaluate the proposed algorithm both in simulation and using multi-contrast (T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR)) clinical low-field MRI data from an LMIC hospital. We show the efficacy of IQT in improving contrast and resolution of low-field MR images. We demonstrate that IQT-enhanced images have potential for enhancing visualisation of anatomical structures and pathological lesions of clinical relevance from the perspective of radiologists. IQT is proved to have capability of boosting the diagnostic value of low-field MRI, especially in low-resource settings., Comment: Accepted in Medical Image Analysis

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.

Recent advances in MRI have led to the creation of large datasets. With the increase in data volume, it has become difficult to locate previous scans of the same patient within these datasets (a process known as re-identification). To address this issue, we propose an AI-powered medical imaging retrieval framework called DeepBrainPrint, which is designed to retrieve brain MRI scans of the same patient. Our framework is a semi-self-supervised contrastive deep learning approach with three main innovations. First, we use a combination of self-supervised and supervised paradigms to create an effective brain fingerprint from MRI scans that can be used for real-time image retrieval. Second, we use a special weighting function to guide the training and improve model convergence. Third, we introduce new imaging transformations to improve retrieval robustness in the presence of intensity variations (i.e. different scan contrasts), and to account for age and disease progression in patients. We tested DeepBrainPrint on a large dataset of T1-weighted brain MRIs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and on a synthetic dataset designed to evaluate retrieval performance with different image modalities. Our results show that DeepBrainPrint outperforms previous methods, including simple similarity metrics and more advanced contrastive deep learning frameworks.

Purpose: We address the challenge of inaccurate parameter estimation in diffusion MRI when the signal-to-noise ratio (SNR) is very low, as in the spinal cord. The accuracy of conventional maximum-likelihood estimation (MLE) depends highly on initialisation. Unfavourable choices could result in suboptimal parameter estimates. Current methods to address this issue, such as grid search (GS) can increase computation time substantially. Methods: We propose a machine learning (ML) informed MLE approach that combines conventional MLE with ML approaches synergistically. ML-based methods have been developed recently to improve the speed and precision of parameter estimation. However, they can generate high systematic bias in estimated parameters when SNR is low. In the proposed ML-MLE approach, an artificial neural network model is trained to provide sensible initialisation for MLE efficiently, with the final solution determined by MLE, avoiding biases typically affecting pure ML estimations. Results: Using parameter estimation of neurite orientation dispersion and density imaging as an example, simulation and in vivo experiments suggest that the ML-MLE method can reduce outlier estimates from conventional MLE in white matter voxels affected by CSF contamination. It also accelerates computation compared to GS-MLE. Conclusion: The ML-MLE method can improve the reliability of parameter estimation with reduced computation time compared to GS-MLE, making it a practical tool for diffusion dataset with low SNR.

Transposed convolution is crucial for generating high-resolution outputs, yet has received little attention compared to convolution layers. In this work we revisit transposed convolution and introduce a novel layer that allows us to place information in the image selectively and choose the `stroke breadth' at which the image is synthesized, whilst incurring a small additional parameter cost. For this we introduce three ideas: firstly, we regress offsets to the positions where the transpose convolution results are placed; secondly we broadcast the offset weight locations over a learnable neighborhood; and thirdly we use a compact parametrization to share weights and restrict offsets. We show that simply substituting upsampling operators with our novel layer produces substantial improvements across tasks as diverse as instance segmentation, object detection, semantic segmentation, generative image modeling, and 3D magnetic resonance image enhancement, while outperforming all existing variants of transposed convolutions. Our novel layer can be used as a drop-in replacement for 2D and 3D upsampling operators and the code will be publicly available.

This paper presents a data-driven, task-specific paradigm for experimental design, to shorten acquisition time, reduce costs, and accelerate the deployment of imaging devices. Current approaches in experimental design focus on model-parameter estimation and require specification of a particular model, whereas in imaging, other tasks may drive the design. Furthermore, such approaches often lead to intractable optimization problems in real-world imaging applications. Here we present a new paradigm for experimental design that simultaneously optimizes the design (set of image channels) and trains a machine-learning model to execute a user-specified image-analysis task. The approach obtains data densely-sampled over the measurement space (many image channels) for a small number of acquisitions, then identifies a subset of channels of prespecified size that best supports the task. We propose a method: TADRED for TAsk-DRiven Experimental Design in imaging, to identify the most informative channel-subset whilst simultaneously training a network to execute the task given the subset. Experiments demonstrate the potential of TADRED in diverse imaging applications: several clinically-relevant tasks in magnetic resonance imaging; and remote sensing and physiological applications of hyperspectral imaging. Results show substantial improvement over classical experimental design, two recent application-specific methods within the new paradigm, and state-of-the-art approaches in supervised feature selection. We anticipate further applications of our approach. Code is available: https://github.com/sbb-gh/experimental-design-multichannel, Comment: Accepted In: International Conference on Learning Representations (ICLR) 2024

Machine learning is a powerful approach for fitting microstructural models to diffusion MRI data. Early machine learning microstructure imaging implementations trained regressors to estimate model parameters in a supervised way, using synthetic training data with known ground truth. However, a drawback of this approach is that the choice of training data impacts fitted parameter values. Self-supervised learning is emerging as an attractive alternative to supervised learning in this context. Thus far, both supervised and self-supervised learning have typically been applied to isotropic models, such as intravoxel incoherent motion (IVIM), as opposed to models where the directionality of anisotropic structures is also estimated. In this paper, we demonstrate self-supervised machine learning model fitting for a directional microstructural model. In particular, we fit a combined T1-ball-stick model to the multidimensional diffusion (MUDI) challenge diffusion-relaxation dataset. Our self-supervised approach shows clear improvements in parameter estimation and computational time, for both simulated and in-vivo brain data, compared to standard non-linear least squares fitting. Code for the artificial neural net constructed for this study is available for public use from the following GitHub repository: https://github.com/jplte/deep-T1-ball-stick, Comment: Oral Presentation in: Computational Diffusion MRI Workshop (CDMRI) at Medical Image Computing and Computer Assisted Intervention (MICCAI) 2022

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%.

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., Comment: MICCAI 2022 (Early accept, Student Travel Award)

Large medical imaging data sets are becoming increasingly available, but ensuring sample quality without significant artefacts is challenging. Existing methods for identifying imperfections in medical imaging rely on data-intensive approaches, compounded by a scarcity of artefact-rich scans for training machine learning models in clinical research. To tackle this problem, we propose a framework with four main components: 1) artefact generators inspired by magnetic resonance physics to corrupt brain MRI scans and augment a training dataset, 2) abstract and engineered features to represent images compactly, 3) a feature selection process depending on the artefact class to improve classification, and 4) SVM classifiers to identify artefacts. Our contributions are threefold: first, physics-based artefact generators produce synthetic brain MRI scans with controlled artefacts for data augmentation. This will avoid the labour-intensive collection and labelling process of scans with rare artefacts. Second, we propose a pool of abstract and engineered image features to identify 9 different artefacts for structural MRI. Finally, we use an artefact-based feature selection block that, for each class of artefacts, finds the set of features providing the best classification performance. We performed validation experiments on a large data set of scans with artificially-generated artefacts, and in a multiple sclerosis clinical trial where real artefacts were identified by experts, showing that the proposed pipeline outperforms traditional methods. In particular, our data augmentation increases performance by up to 12.5 percentage points on accuracy, precision, and recall. The computational efficiency of our pipeline enables potential real-time deployment, promising high-throughput clinical applications through automated image-processing pipelines driven by quality control systems.

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.

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., Comment: Accepted as a full paper at the Medical Imaging with Deep Learning conference (MIDL 2022)

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., Comment: To appear at Conference on Medical Imaging with Deep Learning (MIDL) 2022. arXiv admin note: text overlap with arXiv:2110.12179

We present PROSUB: PROgressive SUBsampling, a deep learning based, automated methodology that subsamples an oversampled data set (e.g. multi-channeled 3D images) with minimal loss of information. We build upon a recent dual-network approach that won the MICCAI MUlti-DIffusion (MUDI) quantitative MRI measurement sampling-reconstruction challenge, but suffers from deep learning training instability, by subsampling with a hard decision boundary. PROSUB uses the paradigm of recursive feature elimination (RFE) and progressively subsamples measurements during deep learning training, improving optimization stability. PROSUB also integrates a neural architecture search (NAS) paradigm, allowing the network architecture hyperparameters to respond to the subsampling process. We show PROSUB outperforms the winner of the MUDI MICCAI challenge, producing large improvements >18% MSE on the MUDI challenge sub-tasks and qualitative improvements on downstream processes useful for clinical applications. We also show the benefits of incorporating NAS and analyze the effect of PROSUB's components. As our method generalizes to other problems beyond MRI measurement selection-reconstruction, our code is https://github.com/sbb-gh/PROSUB, Comment: Accepted In: Medical Image Computing and Computer Assisted Intervention (MICCAI) 2022

Estimating clinically-relevant vascular features following vessel segmentation is a standard pipeline for retinal vessel analysis, which provides potential ocular biomarkers for both ophthalmic disease and systemic disease. In this work, we integrate these clinical features into a novel vascular feature optimised loss function (VAFO-Loss), in order to regularise networks to produce segmentation maps, with which more accurate vascular features can be derived. Two common vascular features, vessel density and fractal dimension, are identified to be sensitive to intra-segment misclassification, which is a well-recognised problem in multi-class artery/vein segmentation particularly hindering the estimation of these vascular features. Thus we encode these two features into VAFO-Loss. We first show that incorporating our end-to-end VAFO-Loss in standard segmentation networks indeed improves vascular feature estimation, yielding quantitative improvement in stroke incidence prediction, a clinical downstream task. We also report a technically interesting finding that the trained segmentation network, albeit biased by the feature optimised loss VAFO-Loss, shows statistically significant improvement in segmentation metrics, compared to those trained with other state-of-the-art segmentation losses., Comment: 13 pages, 6 figures, 3 tables

Machine learning methods exploiting multi-parametric biomarkers, especially based on neuroimaging, have huge potential to improve early diagnosis of dementia and to predict which individuals are at-risk of developing dementia. To benchmark algorithms in the field of machine learning and neuroimaging in dementia and assess their potential for use in clinical practice and clinical trials, seven grand challenges have been organized in the last decade. The seven grand challenges addressed questions related to screening, clinical status estimation, prediction and monitoring in (pre-clinical) dementia. There was little overlap in clinical questions, tasks and performance metrics. Whereas this aids providing insight on a broad range of questions, it also limits the validation of results across challenges. The validation process itself was mostly comparable between challenges, using similar methods for ensuring objective comparison, uncertainty estimation and statistical testing. In general, winning algorithms performed rigorous data preprocessing and combined a wide range of input features. Despite high state-of-the-art performances, most of the methods evaluated by the challenges are not clinically used. To increase impact, future challenges could pay more attention to statistical analysis of which factors relate to higher performance, to clinical questions beyond Alzheimer's disease, and to using testing data beyond the Alzheimer's Disease Neuroimaging Initiative. Grand challenges would be an ideal venue for assessing the generalizability of algorithm performance to unseen data of other cohorts. Key for increasing impact in this way are larger testing data sizes, which could be reached by sharing algorithms rather than data to exploit data that cannot be shared., Comment: 12 pages, 4 tables

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., Comment: 14 pages, 8 Figures, for associated source code, see https://github.com/ashkanpakzad/AirQuant

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., Comment: To appear in IEEE Transactions on Medical Imaging 2023

Many computer vision systems require low-cost segmentation algorithms based on deep learning, either because of the enormous size of input images or limited computational budget. Common solutions uniformly downsample the input images to meet memory constraints, assuming all pixels are equally informative. In this work, we demonstrate that this assumption can harm the segmentation performance because the segmentation difficulty varies spatially. We combat this problem by introducing a learnable downsampling module, which can be optimised together with the given segmentation model in an end-to-end fashion. We formulate the problem of training such downsampling module as optimisation of sampling density distributions over the input images given their low-resolution views. To defend against degenerate solutions (e.g. over-sampling trivial regions like the backgrounds), we propose a regularisation term that encourages the sampling locations to concentrate around the object boundaries. We find the downsampling module learns to sample more densely at difficult locations, thereby improving the segmentation performance. Our experiments on benchmarks of high-resolution street view, aerial and medical images demonstrate substantial improvements in terms of efficiency-and-accuracy trade-off compared to both uniform downsampling and two recent advanced downsampling techniques., Comment: 19 pages, 17 figures

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, Comment: 13 pages, 9 figures, and 2 tables

Landmark correspondences are a widely used type of gold standard in image registration. However, the manual placement of corresponding points is subject to high inter-user variability in the chosen annotated locations and in the interpretation of visual ambiguities. In this paper, we introduce a principled strategy for the construction of a gold standard in deformable registration. Our framework: (i) iteratively suggests the most informative location to annotate next, taking into account its redundancy with previous annotations; (ii) extends traditional pointwise annotations by accounting for the spatial uncertainty of each annotation, which can either be directly specified by the user, or aggregated from pointwise annotations from multiple experts; and (iii) naturally provides a new strategy for the evaluation of deformable registration algorithms. Our approach is validated on four different registration tasks. The experimental results show the efficacy of suggesting annotations according to their informativeness, and an improved capacity to assess the quality of the outputs of registration algorithms. In addition, our approach yields, from sparse annotations only, a dense visualization of the errors made by a registration method. The source code of our approach supporting both 2D and 3D data is publicly available at https://github.com/LoicPeter/evaluation-deformable-registration., Comment: Accepted at IEEE Transactions on Medical Imaging

Axons in white matter have been shown to have varying geometries within a bundle using ex vivo imaging techniques, but what does this mean for diffusion MRI (dMRI) based spherical deconvolution (SD)? SD attempts to estimate the fibre orientation distribution function (fODF) by assuming a single dMRI fibre response function (FRF) for all white matter populations and deconvolving this FRF from the dMRI signal at each voxel to estimate the fODF. Variable fibre geometry within a bundle however suggests the FRF might not be constant even within a single voxel. We test what impact realistic fibre geometry has on SD by simulating the dMRI signal in a range of realistic white matter numerical phantoms, including synthetic phantoms and real axons segmented from electron microscopy. We demonstrate that variable fibre geometry leads to a variable FRF across axons and that in general no single FRF is effective to recover the underlying fibre orientation distribution function (fODF). This finding suggests that assuming a single FRF can lead to misestimation of the fODF, causing further downstream errors in techniques such as tractography.