Matthew Sinclair

Yiyang Xu, Hao Xu, Matthew Sinclair et al.

Cardiac magnetic resonance (CMR) imaging and computed tomography (CT) are two common non-invasive imaging methods for assessing patients with cardiovascular disease. CMR typically acquires multiple sparse 2D slices, with unavoidable respiratory motion artefacts between slices, whereas CT acquires isotropic dense data but uses ionising radiation. In this study, we explore the combination of Slice Shifting Algorithm (SSA), Spatial Transformer Network (STN), and Label Transformer Network (LTN) to: 1) correct respiratory motion between segmented slices, and 2) transform sparse segmentation data into dense segmentation. All combinations were validated using synthetic motion-corrupted CMR slice segmentation generated from CT in 1699 cases, where the dense CT serves as the ground truth. In 199 testing cases, SSA-LTN achieved the best results for Dice score and Huasdorff distance (94.0% and 4.7 mm respectively, average over 5 labels) but gave topological errors in 8 cases. STN was effective as a plug-in tool for correcting all topological errors with minimal impact on overall performance (93.5% and 5.0 mm respectively). SSA also proves to be a valuable plug-in tool, enhancing performance over both STN-based and LTN-based models. The code for these different combinations is available at https://github.com/XESchong/STACOM2024.

Liu Li, Qiang Ma, Matthew Sinclair et al.

Fetal Magnetic Resonance Imaging (MRI) is used in prenatal diagnosis and to assess early brain development. Accurate segmentation of the different brain tissues is a vital step in several brain analysis tasks, such as cortical surface reconstruction and tissue thickness measurements. Fetal MRI scans, however, are prone to motion artifacts that can affect the correctness of both manual and automatic segmentation techniques. In this paper, we propose a novel network structure that can simultaneously generate conditional atlases and predict brain tissue segmentation, called CAS-Net. The conditional atlases provide anatomical priors that can constrain the segmentation connectivity, despite the heterogeneity of intensity values caused by motion or partial volume effects. The proposed method is trained and evaluated on 253 subjects from the developing Human Connectome Project (dHCP). The results demonstrate that the proposed method can generate conditional age-specific atlas with sharp boundary and shape variance. It also segment multi-category brain tissues for fetal MRI with a high overall Dice similarity coefficient (DSC) of $85.2\%$ for the selected 9 tissue labels.

Jingjie Guo, Weitong Zhang, Matthew Sinclair et al.

Convolutional neural networks (CNNs) often suffer from poor performance when tested on target data that differs from the training (source) data distribution, particularly in medical imaging applications where variations in imaging protocols across different clinical sites and scanners lead to different imaging appearances. However, re-accessing source training data for unsupervised domain adaptation or labeling additional test data for model fine-tuning can be difficult due to privacy issues and high labeling costs, respectively. To solve this problem, we propose a novel atlas-guided test-time adaptation (TTA) method for robust 3D medical image segmentation, called AdaAtlas. AdaAtlas only takes one single unlabeled test sample as input and adapts the segmentation network by minimizing an atlas-based loss. Specifically, the network is adapted so that its prediction after registration is aligned with the learned atlas in the atlas space, which helps to reduce anatomical segmentation errors at test time. In addition, different from most existing TTA methods which restrict the adaptation to batch normalization blocks in the segmentation network only, we further exploit the use of channel and spatial attention blocks for improved adaptability at test time. Extensive experiments on multiple datasets from different sites show that AdaAtlas with attention blocks adapted (AdaAtlas-Attention) achieves superior performance improvements, greatly outperforming other competitive TTA methods.

James Batten, Matthew Sinclair, Ben Glocker et al.

Extracting complex structures from grid-based data is a common key step in automated medical image analysis. The conventional solution to recovering tree-structured geometries typically involves computing the minimal cost path through intermediate representations derived from segmentation masks. However, this methodology has significant limitations in the context of projective imaging of tree-structured 3D anatomical data such as coronary arteries, since there are often overlapping branches in the 2D projection. In this work, we propose a novel approach to predicting tree connectivity structure which reformulates the task as an optimization problem over individual steps of a recursive process. We design and train a two-stage model which leverages the UNet and Transformer architectures and introduces an image-based prompting technique. Our proposed method achieves compelling results on a pair of synthetic datasets, and outperforms a shortest-path baseline.

Matthew Sinclair, Moeen Meigooni, Archit Vasan et al.

Intrinsically disordered proteins (IDPs) represent crucial therapeutic targets due to their significant role in disease -- approximately 80\% of cancer-related proteins contain long disordered regions -- but their lack of stable secondary/tertiary structures makes them "undruggable". While recent computational advances, such as diffusion models, can design high-affinity IDP binders, translating these to practical drug discovery requires autonomous systems capable of reasoning across complex conformational ensembles and orchestrating diverse computational tools at scale.To address this challenge, we designed and implemented StructBioReasoner, a scalable multi-agent system for designing biologics that can be used to target IDPs. StructBioReasoner employs a novel tournament-based reasoning framework where specialized agents compete to generate and refine therapeutic hypotheses, naturally distributing computational load for efficient exploration of the vast design space. Agents integrate domain knowledge with access to literature synthesis, AI-structure prediction, molecular simulations, and stability analysis, coordinating their execution on HPC infrastructure via an extensible federated agentic middleware, Academy. We benchmark StructBioReasoner across Der f 21 and NMNAT-2 and demonstrate that over 50\% of 787 designed and validated candidates for Der f 21 outperformed the human-designed reference binders from literature, in terms of improved binding free energy. For the more challenging NMNAT-2 protein, we identified three binding modes from 97,066 binders, including the well-studied NMNAT2:p53 interface. Thus, StructBioReasoner lays the groundwork for agentic reasoning systems for IDP therapeutic discovery on Exascale platforms.

Tian Xia, Matthew Sinclair, Andreas Schuh et al.

Counterfactual image generation enables controlled data augmentation, bias mitigation, and disease modeling. However, existing methods guided by external classifiers or regressors are limited to subject-level factors (e.g., age) and fail to produce localized structural changes, often resulting in global artifacts. Pixel-level guidance using segmentation masks has been explored, but requires user-defined counterfactual masks, which are tedious and impractical. Segmentor-guided Counterfactual Fine-Tuning (Seg-CFT) addressed this by using segmentation-derived measurements to supervise structure-specific variables, yet it remains restricted to global interventions. We propose Positional Seg-CFT, which subdivides each structure into regional segments and derives independent measurements per region, enabling spatially localized and anatomically coherent counterfactuals. Experiments on coronary CT angiography show that Pos-Seg-CFT generates realistic, region-specific modifications, providing finer spatial control for modeling disease progression.

Tian Xia, Matthew Sinclair, Andreas Schuh et al.

Counterfactual image generation is a powerful tool for augmenting training data, de-biasing datasets, and modeling disease. Current approaches rely on external classifiers or regressors to increase the effectiveness of subject-level interventions (e.g., changing the patient's age). For structure-specific interventions (e.g., changing the area of the left lung in a chest radiograph), we show that this is insufficient, and can result in undesirable global effects across the image domain. Previous work used pixel-level label maps as guidance, requiring a user to provide hypothetical segmentations which are tedious and difficult to obtain. We propose Segmentor-guided Counterfactual Fine-Tuning (Seg-CFT), which preserves the simplicity of intervening on scalar-valued, structure-specific variables while producing locally coherent and effective counterfactuals. We demonstrate the capability of generating realistic chest radiographs, and we show promising results for modeling coronary artery disease. Code: https://github.com/biomedia-mira/seg-cft.

Yuanwei Li, Bishesh Khanal, Benjamin Hou et al.

Standard scan plane detection in fetal brain ultrasound (US) forms a crucial step in the assessment of fetal development. In clinical settings, this is done by manually manoeuvring a 2D probe to the desired scan plane. With the advent of 3D US, the entire fetal brain volume containing these standard planes can be easily acquired. However, manual standard plane identification in 3D volume is labour-intensive and requires expert knowledge of fetal anatomy. We propose a new Iterative Transformation Network (ITN) for the automatic detection of standard planes in 3D volumes. ITN uses a convolutional neural network to learn the relationship between a 2D plane image and the transformation parameters required to move that plane towards the location/orientation of the standard plane in the 3D volume. During inference, the current plane image is passed iteratively to the network until it converges to the standard plane location. We explore the effect of using different transformation representations as regression outputs of ITN. Under a multi-task learning framework, we introduce additional classification probability outputs to the network to act as confidence measures for the regressed transformation parameters in order to further improve the localisation accuracy. When evaluated on 72 US volumes of fetal brain, our method achieves an error of 3.83mm/12.7 degrees and 3.80mm/12.6 degrees for the transventricular and transcerebellar planes respectively and takes 0.46s per plane. Source code is publicly available at https://github.com/yuanwei1989/plane-detection.

Yuanwei Li, Amir Alansary, Juan J. Cerrolaza et al.

We propose a new Patch-based Iterative Network (PIN) for fast and accurate landmark localisation in 3D medical volumes. PIN utilises a Convolutional Neural Network (CNN) to learn the spatial relationship between an image patch and anatomical landmark positions. During inference, patches are repeatedly passed to the CNN until the estimated landmark position converges to the true landmark location. PIN is computationally efficient since the inference stage only selectively samples a small number of patches in an iterative fashion rather than a dense sampling at every location in the volume. Our approach adopts a multi-task learning framework that combines regression and classification to improve localisation accuracy. We extend PIN to localise multiple landmarks by using principal component analysis, which models the global anatomical relationships between landmarks. We have evaluated PIN using 72 3D ultrasound images from fetal screening examinations. PIN achieves quantitatively an average landmark localisation error of 5.59mm and a runtime of 0.44s to predict 10 landmarks per volume. Qualitatively, anatomical 2D standard scan planes derived from the predicted landmark locations are visually similar to the clinical ground truth. Source code is publicly available at https://github.com/yuanwei1989/landmark-detection.

James Batten, Michiel Schaap, Matthew Sinclair et al.

We introduce a novel framework for learning vector representations of tree-structured geometric data focusing on 3D vascular networks. Our approach employs two sequentially trained Transformer-based autoencoders. In the first stage, the Vessel Autoencoder captures continuous geometric details of individual vessel segments by learning embeddings from sampled points along each curve. In the second stage, the Vessel Tree Autoencoder encodes the topology of the vascular network as a single vector representation, leveraging the segment-level embeddings from the first model. A recursive decoding process ensures that the reconstructed topology is a valid tree structure. Compared to 3D convolutional models, this proposed approach substantially lowers GPU memory requirements, facilitating large-scale training. Experimental results on a 2D synthetic tree dataset and a 3D coronary artery dataset demonstrate superior reconstruction fidelity, accurate topology preservation, and realistic interpolations in latent space. Our scalable framework, named VeTTA, offers precise, flexible, and topologically consistent modeling of anatomical tree structures in medical imaging.

Samuel Budd, Matthew Sinclair, Thomas Day et al.

Fetal ultrasound screening during pregnancy plays a vital role in the early detection of fetal malformations which have potential long-term health impacts. The level of skill required to diagnose such malformations from live ultrasound during examination is high and resources for screening are often limited. We present an interpretable, atlas-learning segmentation method for automatic diagnosis of Hypo-plastic Left Heart Syndrome (HLHS) from a single `4 Chamber Heart' view image. We propose to extend the recently introduced Image-and-Spatial Transformer Networks (Atlas-ISTN) into a framework that enables sensitising atlas generation to disease. In this framework we can jointly learn image segmentation, registration, atlas construction and disease prediction while providing a maximum level of clinical interpretability compared to direct image classification methods. As a result our segmentation allows diagnoses competitive with expert-derived manual diagnosis and yields an AUC-ROC of 0.978 (1043 cases for training, 260 for validation and 325 for testing).

Matthew Sinclair, Andreas Schuh, Karl Hahn et al.

Deep learning models for semantic segmentation are able to learn powerful representations for pixel-wise predictions, but are sensitive to noise at test time and do not guarantee a plausible topology. Image registration models on the other hand are able to warp known topologies to target images as a means of segmentation, but typically require large amounts of training data, and have not widely been benchmarked against pixel-wise segmentation models. We propose Atlas-ISTN, a framework that jointly learns segmentation and registration on 2D and 3D image data, and constructs a population-derived atlas in the process. Atlas-ISTN learns to segment multiple structures of interest and to register the constructed, topologically consistent atlas labelmap to an intermediate pixel-wise segmentation. Additionally, Atlas-ISTN allows for test time refinement of the model's parameters to optimize the alignment of the atlas labelmap to an intermediate pixel-wise segmentation. This process both mitigates for noise in the target image that can result in spurious pixel-wise predictions, as well as improves upon the one-pass prediction of the model. Benefits of the Atlas-ISTN framework are demonstrated qualitatively and quantitatively on 2D synthetic data and 3D cardiac computed tomography and brain magnetic resonance image data, out-performing both segmentation and registration baseline models. Atlas-ISTN also provides inter-subject correspondence of the structures of interest, enabling population-level shape and motion analysis.

Esther Puyol Anton, Bram Ruijsink, Christian F. Baumgartner et al.

Tissue characterisation with CMR parametric mapping has the potential to detect and quantify both focal and diffuse alterations in myocardial structure not assessable by late gadolinium enhancement. Native T1 mapping in particular has shown promise as a useful biomarker to support diagnostic, therapeutic and prognostic decision-making in ischaemic and non-ischaemic cardiomyopathies. Convolutional neural networks with Bayesian inference are a category of artificial neural networks which model the uncertainty of the network output. This study presents an automated framework for tissue characterisation from native ShMOLLI T1 mapping at 1.5T using a Probabilistic Hierarchical Segmentation (PHiSeg) network. In addition, we use the uncertainty information provided by the PHiSeg network in a novel automated quality control (QC) step to identify uncertain T1 values. The PHiSeg network and QC were validated against manual analysis on a cohort of the UK Biobank containing healthy subjects and chronic cardiomyopathy patients. We used the proposed method to obtain reference T1 ranges for the left ventricular myocardium in healthy subjects as well as common clinical cardiac conditions. T1 values computed from automatic and manual segmentations were highly correlated (r=0.97). Bland-Altman analysis showed good agreement between the automated and manual measurements. The average Dice metric was 0.84 for the left ventricular myocardium. The sensitivity of detection of erroneous outputs was 91%. Finally, T1 values were automatically derived from 14,683 CMR exams from the UK Biobank. The proposed pipeline allows for automatic analysis of myocardial native T1 mapping and includes a QC process to detect potentially erroneous results. T1 reference values were presented for healthy subjects and common clinical cardiac conditions from the largest cohort to date using T1-mapping images.

Samuel Budd, Matthew Sinclair, Bishesh Khanal et al.

Manual estimation of fetal Head Circumference (HC) from Ultrasound (US) is a key biometric for monitoring the healthy development of fetuses. Unfortunately, such measurements are subject to large inter-observer variability, resulting in low early-detection rates of fetal abnormalities. To address this issue, we propose a novel probabilistic Deep Learning approach for real-time automated estimation of fetal HC. This system feeds back statistics on measurement robustness to inform users how confident a deep neural network is in evaluating suitable views acquired during free-hand ultrasound examination. In real-time scenarios, this approach may be exploited to guide operators to scan planes that are as close as possible to the underlying distribution of training images, for the purpose of improving inter-operator consistency. We train on free-hand ultrasound data from over 2000 subjects (2848 training/540 test) and show that our method is able to predict HC measurements within 1.81$\pm$1.65mm deviation from the ground truth, with 50% of the test images fully contained within the predicted confidence margins, and an average of 1.82$\pm$1.78mm deviation from the margin for the remaining cases that are not fully contained.

Qingjie Meng, Matthew Sinclair, Veronika Zimmer et al.

Detecting acoustic shadows in ultrasound images is important in many clinical and engineering applications. Real-time feedback of acoustic shadows can guide sonographers to a standardized diagnostic viewing plane with minimal artifacts and can provide additional information for other automatic image analysis algorithms. However, automatically detecting shadow regions using learning-based algorithms is challenging because pixel-wise ground truth annotation of acoustic shadows is subjective and time consuming. In this paper we propose a weakly supervised method for automatic confidence estimation of acoustic shadow regions. Our method is able to generate a dense shadow-focused confidence map. In our method, a shadow-seg module is built to learn general shadow features for shadow segmentation, based on global image-level annotations as well as a small number of coarse pixel-wise shadow annotations. A transfer function is introduced to extend the obtained binary shadow segmentation to a reference confidence map. Additionally, a confidence estimation network is proposed to learn the mapping between input images and the reference confidence maps. This network is able to predict shadow confidence maps directly from input images during inference. We use evaluation metrics such as DICE, inter-class correlation and etc. to verify the effectiveness of our method. Our method is more consistent than human annotation, and outperforms the state-of-the-art quantitatively in shadow segmentation and qualitatively in confidence estimation of shadow regions. We further demonstrate the applicability of our method by integrating shadow confidence maps into tasks such as ultrasound image classification, multi-view image fusion and automated biometric measurements.

Giacomo Tarroni, Ozan Oktay, Matthew Sinclair et al.

In the clinical routine, short axis (SA) cine cardiac MR (CMR) image stacks are acquired during multiple subsequent breath-holds. If the patient cannot consistently hold the breath at the same position, the acquired image stack will be affected by inter-slice respiratory motion and will not correctly represent the cardiac volume, introducing potential errors in the following analyses and visualisations. We propose an approach to automatically correct inter-slice respiratory motion in SA CMR image stacks. Our approach makes use of probabilistic segmentation maps (PSMs) of the left ventricular (LV) cavity generated with decision forests. PSMs are generated for each slice of the SA stack and rigidly registered in-plane to a target PSM. If long axis (LA) images are available, PSMs are generated for them and combined to create the target PSM; if not, the target PSM is produced from the same stack using a 3D model trained from motion-free stacks. The proposed approach was tested on a dataset of SA stacks acquired from 24 healthy subjects (for which anatomical 3D cardiac images were also available as reference) and compared to two techniques which use LA intensity images and LA segmentations as targets, respectively. The results show the accuracy and robustness of the proposed approach in motion compensation.

Nicolas Toussaint, Bishesh Khanal, Matthew Sinclair et al.

This paper addresses the task of detecting and localising fetal anatomical regions in 2D ultrasound images, where only image-level labels are present at training, i.e. without any localisation or segmentation information. We examine the use of convolutional neural network architectures coupled with soft proposal layers. The resulting network simultaneously performs anatomical region detection (classification) and localisation tasks. We generate a proposal map describing the attention of the network for a particular class. The network is trained on 85,500 2D fetal Ultrasound images and their associated labels. Labels correspond to six anatomical regions: head, spine, thorax, abdomen, limbs, and placenta. Detection achieves an average accuracy of 90\% on individual regions, and show that the proposal maps correlate well with relevant anatomical structures. This work presents itself as a powerful and essential step towards subsequent tasks such as fetal position and pose estimation, organ-specific segmentation, or image-guided navigation. Code and additional material is available at https://ntoussaint.github.io/fetalnav

Matthew Sinclair, Christian F. Baumgartner, Jacqueline Matthew et al.

Measurement of head biometrics from fetal ultrasonography images is of key importance in monitoring the healthy development of fetuses. However, the accurate measurement of relevant anatomical structures is subject to large inter-observer variability in the clinic. To address this issue, an automated method utilizing Fully Convolutional Networks (FCN) is proposed to determine measurements of fetal head circumference (HC) and biparietal diameter (BPD). An FCN was trained on approximately 2000 2D ultrasound images of the head with annotations provided by 45 different sonographers during routine screening examinations to perform semantic segmentation of the head. An ellipse is fitted to the resulting segmentation contours to mimic the annotation typically produced by a sonographer. The model's performance was compared with inter-observer variability, where two experts manually annotated 100 test images. Mean absolute model-expert error was slightly better than inter-observer error for HC (1.99mm vs 2.16mm), and comparable for BPD (0.61mm vs 0.59mm), as well as Dice coefficient (0.980 vs 0.980). Our results demonstrate that the model performs at a level similar to a human expert, and learns to produce accurate predictions from a large dataset annotated by many sonographers. Additionally, measurements are generated in near real-time at 15fps on a GPU, which could speed up clinical workflow for both skilled and trainee sonographers.

Konstantinos Kamnitsas, Wenjia Bai, Enzo Ferrante et al.

Deep learning approaches such as convolutional neural nets have consistently outperformed previous methods on challenging tasks such as dense, semantic segmentation. However, the various proposed networks perform differently, with behaviour largely influenced by architectural choices and training settings. This paper explores Ensembles of Multiple Models and Architectures (EMMA) for robust performance through aggregation of predictions from a wide range of methods. The approach reduces the influence of the meta-parameters of individual models and the risk of overfitting the configuration to a particular database. EMMA can be seen as an unbiased, generic deep learning model which is shown to yield excellent performance, winning the first position in the BRATS 2017 competition among 50+ participating teams.

Wenjia Bai, Matthew Sinclair, Giacomo Tarroni et al.

Cardiovascular magnetic resonance (CMR) imaging is a standard imaging modality for assessing cardiovascular diseases (CVDs), the leading cause of death globally. CMR enables accurate quantification of the cardiac chamber volume, ejection fraction and myocardial mass, providing information for diagnosis and monitoring of CVDs. However, for years, clinicians have been relying on manual approaches for CMR image analysis, which is time consuming and prone to subjective errors. It is a major clinical challenge to automatically derive quantitative and clinically relevant information from CMR images. Deep neural networks have shown a great potential in image pattern recognition and segmentation for a variety of tasks. Here we demonstrate an automated analysis method for CMR images, which is based on a fully convolutional network (FCN). The network is trained and evaluated on a large-scale dataset from the UK Biobank, consisting of 4,875 subjects with 93,500 pixelwise annotated images. The performance of the method has been evaluated using a number of technical metrics, including the Dice metric, mean contour distance and Hausdorff distance, as well as clinically relevant measures, including left ventricle (LV) end-diastolic volume (LVEDV) and end-systolic volume (LVESV), LV mass (LVM); right ventricle (RV) end-diastolic volume (RVEDV) and end-systolic volume (RVESV). By combining FCN with a large-scale annotated dataset, the proposed automated method achieves a high performance on par with human experts in segmenting the LV and RV on short-axis CMR images and the left atrium (LA) and right atrium (RA) on long-axis CMR images.