Andrew J. Reader

Iman Islam, Bram Ruijsink, Andrew J. Reader et al.

Deep learning-based medical image segmentation typically relies on ground truth (GT) labels obtained through manual annotation, but these can be prone to random errors or systematic biases. This study examines the robustness of deep learning models to such errors in echocardiography (echo) segmentation and evaluates a novel strategy for detecting and refurbishing erroneous labels during model training. Using the CAMUS dataset, we simulate three error types, then compare a loss-based GT label error detection method with one based on Variance of Gradients (VOG). We also propose a pseudo-labelling approach to refurbish suspected erroneous GT labels. We assess the performance of our proposed approach under varying error levels. Results show that VOG proved highly effective in flagging erroneous GT labels during training. However, a standard U-Net maintained strong performance under random label errors and moderate levels of systematic errors (up to 50%). The detection and refurbishment approach improved performance, particularly under high-error conditions.

George Webber, Alexander Denker, Riccardo Barbano et al.

Flow-based generative models provide strong unconditional priors for inverse problems, but guiding their dynamics for conditional generation remains challenging. Recent work casts training-free conditional generation in flow models as an optimal control problem; however, solving the resulting trajectory optimisation is computationally and memory intensive, requiring differentiation through the flow dynamics or adjoint solves. We propose MPC-Flow, a model predictive control framework that formulates inverse problem solving with flow-based generative models as a sequence of control sub-problems, enabling practical optimal control-based guidance at inference time. We provide theoretical guarantees linking MPC-Flow to the underlying optimal control objective and show how different algorithmic choices yield a spectrum of guidance algorithms, including regimes that avoid backpropagation through the generative model trajectory. We evaluate MPC-Flow on benchmark image restoration tasks, spanning linear and non-linear settings such as in-painting, deblurring, and super-resolution, and demonstrate strong performance and scalability to massive state-of-the-art architectures via training-free guidance of FLUX.2 (32B) in a quantised setting on consumer hardware.

Iman Islam, Esther Puyol-Antón, Bram Ruijsink et al.

Echocardiography is the first imaging modality used for assessing cardiac function, and accurate segmentation of cardiac structures is essential for deriving biomarkers. However, the development of effective automated segmentation models for multiple cardiac structures is challenged by the difficulty of training on datasets from different sources that are often partially-labelled. This study aims to address this challenge by evaluating the performance of three loss functions - adaptive categorical cross entropy (aCCE) loss, marginal loss, and the adaptive binary cross entropy (aBCE) loss - in handling partially-labelled data. We conduct a comprehensive comparison of these loss functions across multiple scenarios and network architectures: intra-domain and inter-domain tasks, with both single and multiple partial-labels, and varying proportions of fully-labelled to partially-labelled data. Our experiments reveal that all three loss functions exhibit strong performance in intra-domain segmentation tasks, effectively handling label variations within the same domain. For inter-domain tasks, where models are trained on datasets with a domain shift, the aBCE and marginal losses show superior performance when dealing with the case of one label being missing from some training examples. In scenarios involving more than one label being missing, marginal loss outperforms the other methods, demonstrating its robustness in such complex conditions. These results highlight the strengths of each loss function depending on the labelling scenario, emphasizing the importance of selecting the appropriate loss function to optimize model performance. This study represents the first investigation of techniques for handling partially-labelled data from multiple different domains in echocardiography segmentation and provides a comprehensive comparison of loss-based solutions.

George Webber, Yuya Mizuno, Oliver D. Howes et al.

Medical image reconstruction with pre-trained score-based generative models (SGMs) has advantages over other existing state-of-the-art deep-learned reconstruction methods, including improved resilience to different scanner setups and advanced image distribution modeling. SGM-based reconstruction has recently been applied to simulated positron emission tomography (PET) datasets, showing improved contrast recovery for out-of-distribution lesions relative to the state-of-the-art. However, existing methods for SGM-based reconstruction from PET data suffer from slow reconstruction, burdensome hyperparameter tuning and slice inconsistency effects (in 3D). In this work, we propose a practical methodology for fully 3D reconstruction that accelerates reconstruction and reduces the number of critical hyperparameters by matching the likelihood of an SGM's reverse diffusion process to a current iterate of the maximum-likelihood expectation maximization algorithm. Using the example of low-count reconstruction from simulated [$^{18}$F]DPA-714 datasets, we show our methodology can match or improve on the NRMSE and SSIM of existing state-of-the-art SGM-based PET reconstruction while reducing reconstruction time and the need for hyperparameter tuning. We evaluate our methodology against state-of-the-art supervised and conventional reconstruction algorithms. Finally, we demonstrate a first-ever implementation of SGM-based reconstruction for real 3D PET data, specifically [$^{18}$F]DPA-714 data, where we integrate perpendicular pre-trained SGMs to eliminate slice inconsistency issues.

George Webber, Yuya Mizuno, Oliver D. Howes et al.

Score-based generative models (SGMs) have recently shown promising results for image reconstruction on simulated positron emission tomography (PET) datasets. In this work we have developed and implemented practical methodology for 3D image reconstruction with SGMs, and perform (to our knowledge) the first SGM-based reconstruction of real fully 3D PET data. We train an SGM on full-count reference brain images, and extend methodology to allow SGM-based reconstructions at very low counts (1% of original, to simulate low-dose or short-duration scanning). We then perform reconstructions for multiple independent realisations of 1% count data, allowing us to analyse the bias and variance characteristics of the method. We sample from the learned posterior distribution of the generative algorithm to calculate uncertainty images for our reconstructions. We evaluate the method's performance on real full- and low-count PET data and compare with conventional OSEM and MAP-EM baselines, showing that our SGM-based low-count reconstructions match full-dose reconstructions more closely and in a bias-variance trade-off comparison, our SGM-reconstructed images have lower variance than existing baselines. Future work will compare to supervised deep-learned methods, with other avenues for investigation including how data conditioning affects the SGM's posterior distribution and the algorithm's performance with different tracers.

George Webber, Alexander Hammers, Andrew P. King et al.

Recent work has shown improved lesion detectability and flexibility to reconstruction hyperparameters (e.g. scanner geometry or dose level) when PET images are reconstructed by leveraging pre-trained diffusion models. Such methods train a diffusion model (without sinogram data) on high-quality, but still noisy, PET images. In this work, we propose a simple method for generating subject-specific PET images from a dataset of multi-subject PET-MR scans, synthesizing "pseudo-PET" images by transforming between different patients' anatomy using image registration. The images we synthesize retain information from the subject's MR scan, leading to higher resolution and the retention of anatomical features compared to the original set of PET images. With simulated and real [$^{18}$F]FDG datasets, we show that pre-training a personalized diffusion model with subject-specific "pseudo-PET" images improves reconstruction accuracy with low-count data. In particular, the method shows promise in combining information from a guidance MR scan without overly imposing anatomical features, demonstrating an improved trade-off between reconstructing PET-unique image features versus features present in both PET and MR. We believe this approach for generating and utilizing synthetic data has further applications to medical imaging tasks, particularly because patient-specific PET images can be generated without resorting to generative deep learning or large training datasets.

George Webber, Yuya Mizuno, Oliver D. Howes et al.

Large high-quality medical image datasets are difficult to acquire but necessary for many deep learning applications. For positron emission tomography (PET), reconstructed image quality is limited by inherent Poisson noise. We propose a novel method for synthesising diverse and realistic pseudo-PET images with improved signal-to-noise ratio. We also show how our pseudo-PET images may be exploited as a generative prior for single-subject PET image reconstruction. Firstly, we perform deep-learned deformable registration of multi-subject magnetic resonance (MR) images paired to multi-subject PET images. We then use the anatomically-learned deformation fields to transform multiple PET images to the same reference space, before averaging random subsets of the transformed multi-subject data to form a large number of varying pseudo-PET images. We observe that using MR information for registration imbues the resulting pseudo-PET images with improved anatomical detail compared to the originals. We consider applications to PET image reconstruction, by generating pseudo-PET images in the same space as the intended single-subject reconstruction and using them as training data for a diffusion model-based reconstruction method. We show visual improvement and reduced background noise in our 2D reconstructions as compared to OSEM, MAP-EM and an existing state-of-the-art diffusion model-based approach. Our method shows the potential for utilising highly subject-specific prior information within a generative reconstruction framework. Future work may compare the benefits of our approach to explicitly MR-guided reconstruction methodologies.

Iman Islam, Esther Puyol-Antón, Bram Ruijsink et al.

Echocardiography (echo) is the first imaging modality used when assessing cardiac function. The measurement of functional biomarkers from echo relies upon the segmentation of cardiac structures and deep learning models have been proposed to automate the segmentation process. However, in order to translate these tools to widespread clinical use it is important that the segmentation models are robust to a wide variety of images (e.g. acquired from different scanners, by operators with different levels of expertise etc.). To achieve this level of robustness it is necessary that the models are trained with multiple diverse datasets. A significant challenge faced when training with multiple diverse datasets is the variation in label presence, i.e. the combined data are often partially-labelled. Adaptations of the cross entropy loss function have been proposed to deal with partially labelled data. In this paper we show that training naively with such a loss function and multiple diverse datasets can lead to a form of shortcut learning, where the model associates label presence with domain characteristics, leading to a drop in performance. To address this problem, we propose a novel label dropout scheme to break the link between domain characteristics and the presence or absence of labels. We demonstrate that label dropout improves echo segmentation Dice score by 62% and 25% on two cardiac structures when training using multiple diverse partially labelled datasets.

George Webber, Alexander Hammers, Andrew P. King et al.

Diffusion models have recently enabled state-of-the-art reconstruction of positron emission tomography (PET) images while requiring only image training data. However, domain shift remains a key concern for clinical adoption: priors trained on images from one anatomy, acquisition protocol or pathology may produce artefacts on out-of-distribution data. We propose integrating steerable conditional diffusion (SCD) with our previously-introduced likelihood-scheduled diffusion (PET-LiSch) framework to improve the alignment of the diffusion model's prior to the target subject. At reconstruction time, for each diffusion step, we use low-rank adaptation (LoRA) to align the diffusion model prior with the target domain on the fly. Experiments on realistic synthetic 2D brain phantoms demonstrate that our approach suppresses hallucinated artefacts under domain shift, i.e. when our diffusion model is trained on perturbed images and tested on normal anatomy, our approach suppresses the hallucinated structure, outperforming both OSEM and diffusion model baselines qualitatively and quantitatively. These results provide a proof-of-concept that steerable priors can mitigate domain shift in diffusion-based PET reconstruction and motivate future evaluation on real data.

George Webber, Alexander Hammers, Andrew P King et al.

Diffusion models (DMs) have recently been introduced as a regularizing prior for PET image reconstruction, integrating DMs trained on high-quality PET images with unsupervised schemes that condition on measured data. While these approaches have potential generalization advantages due to their independence from the scanner geometry and the injected activity level, they forgo the opportunity to explicitly model the interaction between the DM prior and noisy measurement data, potentially limiting reconstruction accuracy. To address this, we propose a supervised DM-based algorithm for PET reconstruction. Our method enforces the non-negativity of PET's Poisson likelihood model and accommodates the wide intensity range of PET images. Through experiments on realistic brain PET phantoms, we demonstrate that our approach outperforms or matches state-of-the-art deep learning-based methods quantitatively across a range of dose levels. We further conduct ablation studies to demonstrate the benefits of the proposed components in our model, as well as its dependence on training data, parameter count, and number of diffusion steps. Additionally, we show that our approach enables more accurate posterior sampling than unsupervised DM-based methods, suggesting improved uncertainty estimation. Finally, we extend our methodology to a practical approach for fully 3D PET and present example results from real [$^{18}$F]FDG brain PET data.