Yunguan Fu

M. Jorge Cardoso, Wenqi Li, Richard Brown et al.

Artificial Intelligence (AI) is having a tremendous impact across most areas of science. Applications of AI in healthcare have the potential to improve our ability to detect, diagnose, prognose, and intervene on human disease. For AI models to be used clinically, they need to be made safe, reproducible and robust, and the underlying software framework must be aware of the particularities (e.g. geometry, physiology, physics) of medical data being processed. This work introduces MONAI, a freely available, community-supported, and consortium-led PyTorch-based framework for deep learning in healthcare. MONAI extends PyTorch to support medical data, with a particular focus on imaging, and provide purpose-specific AI model architectures, transformations and utilities that streamline the development and deployment of medical AI models. MONAI follows best practices for software-development, providing an easy-to-use, robust, well-documented, and well-tested software framework. MONAI preserves the simple, additive, and compositional approach of its underlying PyTorch libraries. MONAI is being used by and receiving contributions from research, clinical and industrial teams from around the world, who are pursuing applications spanning nearly every aspect of healthcare.

Yunguan Fu, Yiwen Li, Shaheer U Saeed et al.

Denoising diffusion models have found applications in image segmentation by generating segmented masks conditioned on images. Existing studies predominantly focus on adjusting model architecture or improving inference, such as test-time sampling strategies. In this work, we focus on improving the training strategy and propose a novel recycling method. During each training step, a segmentation mask is first predicted given an image and a random noise. This predicted mask, which replaces the conventional ground truth mask, is used for denoising task during training. This approach can be interpreted as aligning the training strategy with inference by eliminating the dependence on ground truth masks for generating noisy samples. Our proposed method significantly outperforms standard diffusion training, self-conditioning, and existing recycling strategies across multiple medical imaging data sets: muscle ultrasound, abdominal CT, prostate MR, and brain MR. This holds for two widely adopted sampling strategies: denoising diffusion probabilistic model and denoising diffusion implicit model. Importantly, existing diffusion models often display a declining or unstable performance during inference, whereas our novel recycling consistently enhances or maintains performance. We show that, under a fair comparison with the same network architectures and computing budget, the proposed recycling-based diffusion models achieved on-par performance with non-diffusion-based supervised training. By ensembling the proposed diffusion and the non-diffusion models, significant improvements to the non-diffusion models have been observed across all applications, demonstrating the value of this novel training method. This paper summarizes these quantitative results and discusses their values, with a fully reproducible JAX-based implementation, released at https://github.com/mathpluscode/ImgX-DiffSeg.

Yunguan Fu, Yiwen Li, Shaheer U. Saeed et al.

Recently, denoising diffusion probabilistic models (DDPM) have been applied to image segmentation by generating segmentation masks conditioned on images, while the applications were mainly limited to 2D networks without exploiting potential benefits from the 3D formulation. In this work, we studied the DDPM-based segmentation model for 3D multiclass segmentation on two large multiclass data sets (prostate MR and abdominal CT). We observed that the difference between training and test methods led to inferior performance for existing DDPM methods. To mitigate the inconsistency, we proposed a recycling method which generated corrupted masks based on the model's prediction at a previous time step instead of using ground truth. The proposed method achieved statistically significantly improved performance compared to existing DDPMs, independent of a number of other techniques for reducing train-test discrepancy, including performing mask prediction, using Dice loss, and reducing the number of diffusion time steps during training. The performance of diffusion models was also competitive and visually similar to non-diffusion-based U-net, within the same compute budget. The JAX-based diffusion framework has been released at https://github.com/mathpluscode/ImgX-DiffSeg.

Shaheer U. Saeed, Yunguan Fu, Vasilis Stavrinides et al.

In this paper, we consider image quality assessment (IQA) as a measure of how images are amenable with respect to a given downstream task, or task amenability. When the task is performed using machine learning algorithms, such as a neural-network-based task predictor for image classification or segmentation, the performance of the task predictor provides an objective estimate of task amenability. In this work, we use an IQA controller to predict the task amenability which, itself being parameterised by neural networks, can be trained simultaneously with the task predictor. We further develop a meta-reinforcement learning framework to improve the adaptability for both IQA controllers and task predictors, such that they can be fine-tuned efficiently on new datasets or meta-tasks. We demonstrate the efficacy of the proposed task-specific, adaptable IQA approach, using two clinical applications for ultrasound-guided prostate intervention and pneumonia detection on X-ray images.

Qianye Yang, David Atkinson, Yunguan Fu et al.

In this work, we consider the task of pairwise cross-modality image registration, which may benefit from exploiting additional images available only at training time from an additional modality that is different to those being registered. As an example, we focus on aligning intra-subject multiparametric Magnetic Resonance (mpMR) images, between T2-weighted (T2w) scans and diffusion-weighted scans with high b-value (DWI$_{high-b}$). For the application of localising tumours in mpMR images, diffusion scans with zero b-value (DWI$_{b=0}$) are considered easier to register to T2w due to the availability of corresponding features. We propose a learning from privileged modality algorithm, using a training-only imaging modality DWI$_{b=0}$, to support the challenging multi-modality registration problems. We present experimental results based on 369 sets of 3D multiparametric MRI images from 356 prostate cancer patients and report, with statistical significance, a lowered median target registration error of 4.34 mm, when registering the holdout DWI$_{high-b}$ and T2w image pairs, compared with that of 7.96 mm before registration. Results also show that the proposed learning-based registration networks enabled efficient registration with comparable or better accuracy, compared with a classical iterative algorithm and other tested learning-based methods with/without the additional modality. These compared algorithms also failed to produce any significantly improved alignment between DWI$_{high-b}$ and T2w in this challenging application.

Yiwen Li, Yunguan Fu, Iani Gayo et al.

The prowess that makes few-shot learning desirable in medical image analysis is the efficient use of the support image data, which are labelled to classify or segment new classes, a task that otherwise requires substantially more training images and expert annotations. This work describes a fully 3D prototypical few-shot segmentation algorithm, such that the trained networks can be effectively adapted to clinically interesting structures that are absent in training, using only a few labelled images from a different institute. First, to compensate for the widely recognised spatial variability between institutions in episodic adaptation of novel classes, a novel spatial registration mechanism is integrated into prototypical learning, consisting of a segmentation head and an spatial alignment module. Second, to assist the training with observed imperfect alignment, support mask conditioning module is proposed to further utilise the annotation available from the support images. Extensive experiments are presented in an application of segmenting eight anatomical structures important for interventional planning, using a data set of 589 pelvic T2-weighted MR images, acquired at seven institutes. The results demonstrate the efficacy in each of the 3D formulation, the spatial registration, and the support mask conditioning, all of which made positive contributions independently or collectively. Compared with the previously proposed 2D alternatives, the few-shot segmentation performance was improved with statistical significance, regardless whether the support data come from the same or different institutes.

Shaheer U. Saeed, João Ramalhinho, Mark Pinnock et al.

Supervised machine learning-based medical image computing applications necessitate expert label curation, while unlabelled image data might be relatively abundant. Active learning methods aim to prioritise a subset of available image data for expert annotation, for label-efficient model training. We develop a controller neural network that measures priority of images in a sequence of batches, as in batch-mode active learning, for multi-class segmentation tasks. The controller is optimised by rewarding positive task-specific performance gain, within a Markov decision process (MDP) environment that also optimises the task predictor. In this work, the task predictor is a segmentation network. A meta-reinforcement learning algorithm is proposed with multiple MDPs, such that the pre-trained controller can be adapted to a new MDP that contains data from different institutes and/or requires segmentation of different organs or structures within the abdomen. We present experimental results using multiple CT datasets from more than one thousand patients, with segmentation tasks of nine different abdominal organs, to demonstrate the efficacy of the learnt prioritisation controller function and its cross-institute and cross-organ adaptability. We show that the proposed adaptable prioritisation metric yields converging segmentation accuracy for the novel class of kidney, unseen in training, using between approximately 40\% to 60\% of labels otherwise required with other heuristic or random prioritisation metrics. For clinical datasets of limited size, the proposed adaptable prioritisation offers a performance improvement of 22.6\% and 10.2\% in Dice score, for tasks of kidney and liver vessel segmentation, respectively, compared to random prioritisation and alternative active sampling strategies.

Yunguan Fu, Wenjia Bai, Wen Yan et al.

Diffusion-based unsupervised image registration has been explored for cardiac cine MR, but expensive multi-step inference limits practical use. We propose FlowReg, a flow-matching framework in displacement field space that achieves strong registration in as few as two steps and supports further refinement with more steps. FlowReg uses warmup-reflow training: a single-step network first acts as a teacher, then a student learns to refine from arbitrary intermediate states, removing the need for a pre-trained model as in existing methods. An Initial Guess strategy feeds back the model prediction as the next starting point, improving refinement from step two onward. On ACDC and MM2 across six tasks (including cross-dataset generalization), FlowReg outperforms the state of the art on five tasks (+0.6% mean Dice score on average), with the largest gain in the left ventricle (+1.09%), and reduces LVEF estimation error on all six tasks (-2.58 percentage points), using only 0.7% extra parameters and no segmentation labels. Code is available at https://github.com/mathpluscode/FlowReg.

Qian Li, Yunguan Fu, Qianye Yang et al.

Graph neural networks (GNNs) have been proposed for medical image segmentation, by predicting anatomical structures represented by graphs of vertices and edges. One such type of graph is predefined with fixed size and connectivity to represent a reference of anatomical regions of interest, thus known as templates. This work explores the potentials in these GNNs with common topology for establishing spatial correspondence, implicitly maintained during segmenting two or more images. With an example application of registering local vertebral sub-regions found in CT images, our experimental results showed that the GNN-based segmentation is capable of accurate and reliable localization of the same interventionally interesting structures between images, not limited to the segmentation classes. The reported average target registration errors of 2.2$\pm$1.3 mm and 2.7$\pm$1.4 mm, for aligning holdout test images with a reference and for aligning two test images, respectively, were by a considerable margin lower than those from the tested non-learning and learning-based registration algorithms. Further ablation studies assess the contributions towards the registration performance, from individual components in the originally segmentation-purposed network and its training algorithm. The results highlight that the proposed segmentation-in-lieu-of-registration approach shares methodological similarities with existing registration methods, such as the use of displacement smoothness constraint and point distance minimization albeit on non-grid graphs, which interestingly yielded benefits for both segmentation and registration. We, therefore, conclude that the template-based GNN segmentation can effectively establish spatial correspondence in our application, without any other dedicated registration algorithms.

Yunguan Fu, Wenjia Bai, Weixi Yi et al.

Here we present a versatile foundation model that can perform a range of clinically-relevant image analysis tasks, including segmentation, landmark localisation, diagnosis, and prognostication. A multi-view convolution-transformer masked autoencoder, named as CineMA, was trained on 15 million cine images from 74,916 subjects. The model was validated on multiple image analysis tasks and compared to existing models on >4,500 images from eight independent datasets with diverse population characteristics, representing the largest benchmark study for cine CMR so far. CineMA consistently outperformed conventional convolutional neural networks (CNNs) in delineating ventricular boundaries and estimating ejection fraction, a key measure of cardiac function. The improved performance was preserved, even when the model only used half of fine-tuning data. CineMA also surpassed CNNs in disease detection and matched their performance in long-axis function measurement. Interestingly, we found that CineMA can also detect cardiac changes in systemic diseases, such as diabetes, hypertension and cancer, and can also predict mortality. Finally, we assessed model fairness and demonstrated consistent model performance across demographic subgroups. These findings highlight CineMA's accuracy, learning efficiency, adaptability, and fairness, underscoring its potential as a foundation model for automated cardiac image analysis to support clinical workflow and cardiovascular research. All training and inference code and models are made publicly available at https://github.com/mathpluscode/CineMA.

Yucheng Tang, Yunguan Fu, Weixi Yi et al.

Multimodal large language models (MLLMs) can process and integrate information from multimodality sources, such as text and images. However, interrelationship among input modalities, uncertainties due to individual uni-modal data and potential clinical applications following such an uncertainty decomposition are yet fully understood in the context of large-scale MLLMs. In this work, we propose a multimodal uncertainty propagation model (MUPM) based on uncertainty propagation, to characterise the relationship among the uncertainties arising from image-only, text-only, and joint image-text variations in MLLM inputs. Using real clinical data consisting of cardiac MR scans and digital health records, we describe that MUPMs can be optimised robustly with a few samples. We then show that the fitted MUPMs are generalisable across different input data distributions and, perhaps surprisingly, across different downstream tasks. Such a transferability may be explained by the shared pretraining, comparatively light MLLM fine-tuning, along with the low-dimensional nature of the MUPMs. More importantly, this learned transferability, quantifying the relationship between these uncertainties, led to direct clinical applications in which uncertainties may be estimated and thus analysed robustly for varying data or even a novel set of cardiac disease prediction tasks. In addition, we show experimentally the efficiency in multimodal data required for estimating the overall uncertainty and its ability to identify redundant factors, both of which are considered practical yet clinically useful applications with the proposed MUPMs. Codes are available at https://github.com/yucheng722/MUPM.

Yunguan Fu, Nina Montaña Brown, Shaheer U. Saeed et al.

DeepReg (https://github.com/DeepRegNet/DeepReg) is a community-supported open-source toolkit for research and education in medical image registration using deep learning.

Yiwen Li, Yunguan Fu, Iani J. M. B. Gayo et al.

For training registration networks, weak supervision from segmented corresponding regions-of-interest (ROIs) have been proven effective for (a) supplementing unsupervised methods, and (b) being used independently in registration tasks in which unsupervised losses are unavailable or ineffective. This correspondence-informing supervision entails cost in annotation that requires significant specialised effort. This paper describes a semi-weakly-supervised registration pipeline that improves the model performance, when only a small corresponding-ROI-labelled dataset is available, by exploiting unlabelled image pairs. We examine two types of augmentation methods by perturbation on network weights and image resampling, such that consistency-based unsupervised losses can be applied on unlabelled data. The novel WarpDDF and RegCut approaches are proposed to allow commutative perturbation between an image pair and the predicted spatial transformation (i.e. respective input and output of registration networks), distinct from existing perturbation methods for classification or segmentation. Experiments using 589 male pelvic MR images, labelled with eight anatomical ROIs, show the improvement in registration performance and the ablated contributions from the individual strategies. Furthermore, this study attempts to construct one of the first computational atlases for pelvic structures, enabled by registering inter-subject MRs, and quantifies the significant differences due to the proposed semi-weak supervision with a discussion on the potential clinical use of example atlas-derived statistics.

Shaheer U. Saeed, Wen Yan, Yunguan Fu et al.

Image quality assessment (IQA) in medical imaging can be used to ensure that downstream clinical tasks can be reliably performed. Quantifying the impact of an image on the specific target tasks, also named as task amenability, is needed. A task-specific IQA has recently been proposed to learn an image-amenability-predicting controller simultaneously with a target task predictor. This allows for the trained IQA controller to measure the impact an image has on the target task performance, when this task is performed using the predictor, e.g. segmentation and classification neural networks in modern clinical applications. In this work, we propose an extension to this task-specific IQA approach, by adding a task-agnostic IQA based on auto-encoding as the target task. Analysing the intersection between low-quality images, deemed by both the task-specific and task-agnostic IQA, may help to differentiate the underpinning factors that caused the poor target task performance. For example, common imaging artefacts may not adversely affect the target task, which would lead to a low task-agnostic quality and a high task-specific quality, whilst individual cases considered clinically challenging, which can not be improved by better imaging equipment or protocols, is likely to result in a high task-agnostic quality but a low task-specific quality. We first describe a flexible reward shaping strategy which allows for the adjustment of weighting between task-agnostic and task-specific quality scoring. Furthermore, we evaluate the proposed algorithm using a clinically challenging target task of prostate tumour segmentation on multiparametric magnetic resonance (mpMR) images, from 850 patients. The proposed reward shaping strategy, with appropriately weighted task-specific and task-agnostic qualities, successfully identified samples that need re-acquisition due to defected imaging process.

Yiwen Li, Yunguan Fu, Qianye Yang et al.

The ability to adapt medical image segmentation networks for a novel class such as an unseen anatomical or pathological structure, when only a few labelled examples of this class are available from local healthcare providers, is sought-after. This potentially addresses two widely recognised limitations in deploying modern deep learning models to clinical practice, expertise-and-labour-intensive labelling and cross-institution generalisation. This work presents the first 3D few-shot interclass segmentation network for medical images, using a labelled multi-institution dataset from prostate cancer patients with eight regions of interest. We propose an image alignment module registering the predicted segmentation of both query and support data, in a standard prototypical learning algorithm, to a reference atlas space. The built-in registration mechanism can effectively utilise the prior knowledge of consistent anatomy between subjects, regardless whether they are from the same institution or not. Experimental results demonstrated that the proposed registration-assisted prototypical learning significantly improved segmentation accuracy (p-values<0.01) on query data from a holdout institution, with varying availability of support data from multiple institutions. We also report the additional benefits of the proposed 3D networks with 75% fewer parameters and an arguably simpler implementation, compared with existing 2D few-shot approaches that segment 2D slices of volumetric medical images.

Yiwen Li, Gratianus Wesley Putra Data, Yunguan Fu et al.

Despite the success of deep learning methods for semantic segmentation, few-shot semantic segmentation remains a challenging task due to the limited training data and the generalisation requirement for unseen classes. While recent progress has been particularly encouraging, we discover that existing methods tend to have poor performance in terms of meanIoU when query images contain other semantic classes besides the target class. To address this issue, we propose a novel self-supervised task that generates random pseudo-classes in the background of the query images, providing extra training data that would otherwise be unavailable when predicting individual target classes. To that end, we adopted superpixel segmentation for generating the pseudo-classes. With this extra supervision, we improved the meanIoU performance of the state-of-the-art method by 2.5% and 5.1% on the one-shot tasks, as well as 6.7% and 4.4% on the five-shot tasks, on the PASCAL-5i and COCO benchmarks, respectively.

Shaheer U. Saeed, Yunguan Fu, Vasilis Stavrinides et al.

The performance of many medical image analysis tasks are strongly associated with image data quality. When developing modern deep learning algorithms, rather than relying on subjective (human-based) image quality assessment (IQA), task amenability potentially provides an objective measure of task-specific image quality. To predict task amenability, an IQA agent is trained using reinforcement learning (RL) with a simultaneously optimised task predictor, such as a classification or segmentation neural network. In this work, we develop transfer learning or adaptation strategies to increase the adaptability of both the IQA agent and the task predictor so that they are less dependent on high-quality, expert-labelled training data. The proposed transfer learning strategy re-formulates the original RL problem for task amenability in a meta-reinforcement learning (meta-RL) framework. The resulting algorithm facilitates efficient adaptation of the agent to different definitions of image quality, each with its own Markov decision process environment including different images, labels and an adaptable task predictor. Our work demonstrates that the IQA agents pre-trained on non-expert task labels can be adapted to predict task amenability as defined by expert task labels, using only a small set of expert labels. Using 6644 clinical ultrasound images from 249 prostate cancer patients, our results for image classification and segmentation tasks show that the proposed IQA method can be adapted using data with as few as respective 19.7% and 29.6% expert-reviewed consensus labels and still achieve comparable IQA and task performance, which would otherwise require a training dataset with 100% expert labels.

Shaheer U. Saeed, Yunguan Fu, Zachary M. C. Baum et al.

In this paper, we consider a type of image quality assessment as a task-specific measurement, which can be used to select images that are more amenable to a given target task, such as image classification or segmentation. We propose to train simultaneously two neural networks for image selection and a target task using reinforcement learning. A controller network learns an image selection policy by maximising an accumulated reward based on the target task performance on the controller-selected validation set, whilst the target task predictor is optimised using the training set. The trained controller is therefore able to reject those images that lead to poor accuracy in the target task. In this work, we show that the controller-predicted image quality can be significantly different from the task-specific image quality labels that are manually defined by humans. Furthermore, we demonstrate that it is possible to learn effective image quality assessment without using a ``clean'' validation set, thereby avoiding the requirement for human labelling of images with respect to their amenability for the task. Using $6712$, labelled and segmented, clinical ultrasound images from $259$ patients, experimental results on holdout data show that the proposed image quality assessment achieved a mean classification accuracy of $0.94\pm0.01$ and a mean segmentation Dice of $0.89\pm0.02$, by discarding $5\%$ and $15\%$ of the acquired images, respectively. The significantly improved performance was observed for both tested tasks, compared with the respective $0.90\pm0.01$ and $0.82\pm0.02$ from networks without considering task amenability. This enables image quality feedback during real-time ultrasound acquisition among many other medical imaging applications.

Qianye Yang, Tom Vercauteren, Yunguan Fu et al.

Organ morphology is a key indicator for prostate disease diagnosis and prognosis. For instance, In longitudinal study of prostate cancer patients under active surveillance, the volume, boundary smoothness and their changes are closely monitored on time-series MR image data. In this paper, we describe a new framework for forecasting prostate morphological changes, as the ability to detect such changes earlier than what is currently possible may enable timely treatment or avoiding unnecessary confirmatory biopsies. In this work, an efficient feature-based MR image registration is first developed to align delineated prostate gland capsules to quantify the morphological changes using the inferred dense displacement fields (DDFs). We then propose to use kernel density estimation (KDE) of the probability density of the DDF-represented \textit{future morphology changes}, between current and future time points, before the future data become available. The KDE utilises a novel distance function that takes into account morphology, stage-of-progression and duration-of-change, which are considered factors in such subject-specific forecasting. We validate the proposed approach on image masks unseen to registration network training, without using any data acquired at the future target time points. The experiment results are presented on a longitudinal data set with 331 images from 73 patients, yielding an average Dice score of 0.865 on a holdout set, between the ground-truth and the image masks warped by the KDE-predicted-DDFs.

Qianye Yang, Yunguan Fu, Francesco Giganti et al.

Morphological analysis of longitudinal MR images plays a key role in monitoring disease progression for prostate cancer patients, who are placed under an active surveillance program. In this paper, we describe a learning-based image registration algorithm to quantify changes on regions of interest between a pair of images from the same patient, acquired at two different time points. Combining intensity-based similarity and gland segmentation as weak supervision, the population-data-trained registration networks significantly lowered the target registration errors (TREs) on holdout patient data, compared with those before registration and those from an iterative registration algorithm. Furthermore, this work provides a quantitative analysis on several longitudinal-data-sampling strategies and, in turn, we propose a novel regularisation method based on maximum mean discrepancy, between differently-sampled training image pairs. Based on 216 3D MR images from 86 patients, we report a mean TRE of 5.6 mm and show statistically significant differences between the different training data sampling strategies.

Yunguan Fu, Maria R. Robu, Bongjin Koo et al.

Improving a semi-supervised image segmentation task has the option of adding more unlabelled images, labelling the unlabelled images or combining both, as neither image acquisition nor expert labelling can be considered trivial in most clinical applications. With a laparoscopic liver image segmentation application, we investigate the performance impact by altering the quantities of labelled and unlabelled training data, using a semi-supervised segmentation algorithm based on the mean teacher learning paradigm. We first report a significantly higher segmentation accuracy, compared with supervised learning. Interestingly, this comparison reveals that the training strategy adopted in the semi-supervised algorithm is also responsible for this observed improvement, in addition to the added unlabelled data. We then compare different combinations of labelled and unlabelled data set sizes for training semi-supervised segmentation networks, to provide a quantitative example of the practically useful trade-off between the two data planning strategies in this surgical guidance application.

Alexandre Laterre, Yunguan Fu, Mohamed Khalil Jabri et al.

Adversarial self-play in two-player games has delivered impressive results when used with reinforcement learning algorithms that combine deep neural networks and tree search. Algorithms like AlphaZero and Expert Iteration learn tabula-rasa, producing highly informative training data on the fly. However, the self-play training strategy is not directly applicable to single-player games. Recently, several practically important combinatorial optimisation problems, such as the travelling salesman problem and the bin packing problem, have been reformulated as reinforcement learning problems, increasing the importance of enabling the benefits of self-play beyond two-player games. We present the Ranked Reward (R2) algorithm which accomplishes this by ranking the rewards obtained by a single agent over multiple games to create a relative performance metric. Results from applying the R2 algorithm to instances of a two-dimensional and three-dimensional bin packing problems show that it outperforms generic Monte Carlo tree search, heuristic algorithms and integer programming solvers. We also present an analysis of the ranked reward mechanism, in particular, the effects of problem instances with varying difficulty and different ranking thresholds.