Zachary M. C. Baum

Zhe Min, Zachary M. C. Baum, Shaheer U. Saeed et al.

Biomechanical modelling of soft tissue provides a non-data-driven method for constraining medical image registration, such that the estimated spatial transformation is considered biophysically plausible. This has not only been adopted in real-world clinical applications, such as the MR-to-ultrasound registration for prostate intervention of interest in this work, but also provides an explainable means of understanding the organ motion and spatial correspondence establishment. This work instantiates the recently-proposed physics-informed neural networks (PINNs) to a 3D linear elastic model for modelling prostate motion commonly encountered during transrectal ultrasound guided procedures. To overcome a widely-recognised challenge in generalising PINNs to different subjects, we propose to use PointNet as the nodal-permutation-invariant feature extractor, together with a registration algorithm that aligns point sets and simultaneously takes into account the PINN-imposed biomechanics. The proposed method has been both developed and validated in both patient-specific and multi-patient manner.

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.

Zhe Min, Zachary M. C. Baum, Shaheer U. Saeed et al.

This paper investigates both biomechanical-constrained non-rigid medical image registrations and accurate identifications of material properties for soft tissues, using physics-informed neural networks (PINNs). The complex nonlinear elasticity theory is leveraged to formally establish the partial differential equations (PDEs) representing physics laws of biomechanical constraints that need to be satisfied, with which registration and identification tasks are treated as forward (i.e., data-driven solutions of PDEs) and inverse (i.e., parameter estimation) problems under PINNs respectively. Two net configurations (i.e., Cfg1 and Cfg2) have also been compared for both linear and nonlinear physics model. Two sets of experiments have been conducted, using pairs of undeformed and deformed MR images from clinical cases of prostate cancer biopsy. Our contributions are summarised as follows. 1) We developed a learning-based biomechanical-constrained non-rigid registration algorithm using PINNs, where linear elasticity is generalised to the nonlinear version. 2) We demonstrated extensively that nonlinear elasticity shows no statistical significance against linear models in computing point-wise displacement vectors but their respective benefits may depend on specific patients, with finite-element (FE) computed ground-truth. 3) We formulated and solved the inverse parameter estimation problem, under the joint optimisation scheme of registration and parameter identification using PINNs, whose solutions can be accurately found by locating saddle points.

Zachary M. C. Baum, Yipeng Hu, Dean Barratt

We present a meta-learning framework for interactive medical image registration. Our proposed framework comprises three components: a learning-based medical image registration algorithm, a form of user interaction that refines registration at inference, and a meta-learning protocol that learns a rapidly adaptable network initialization. This paper describes a specific algorithm that implements the registration, interaction and meta-learning protocol for our exemplar clinical application: registration of magnetic resonance (MR) imaging to interactively acquired, sparsely-sampled transrectal ultrasound (TRUS) images. Our approach obtains comparable registration error (4.26 mm) to the best-performing non-interactive learning-based 3D-to-3D method (3.97 mm) while requiring only a fraction of the data, and occurring in real-time during acquisition. Applying sparsely sampled data to non-interactive methods yields higher registration errors (6.26 mm), demonstrating the effectiveness of interactive MR-TRUS registration, which may be applied intraoperatively given the real-time nature of the adaptation process.

Weixi Yi, Vasilis Stavrinides, Zachary M. C. Baum et al.

We propose Boundary-RL, a novel weakly supervised segmentation method that utilises only patch-level labels for training. We envision the segmentation as a boundary detection problem, rather than a pixel-level classification as in previous works. This outlook on segmentation may allow for boundary delineation under challenging scenarios such as where noise artefacts may be present within the region-of-interest (ROI) boundaries, where traditional pixel-level classification-based weakly supervised methods may not be able to effectively segment the ROI. Particularly of interest, ultrasound images, where intensity values represent acoustic impedance differences between boundaries, may also benefit from the boundary delineation approach. Our method uses reinforcement learning to train a controller function to localise boundaries of ROIs using a reward derived from a pre-trained boundary-presence classifier. The classifier indicates when an object boundary is encountered within a patch, as the controller modifies the patch location in a sequential Markov decision process. The classifier itself is trained using only binary patch-level labels of object presence, which are the only labels used during training of the entire boundary delineation framework, and serves as a weak signal to inform the boundary delineation. The use of a controller function ensures that a sliding window over the entire image is not necessary. It also prevents possible false-positive or -negative cases by minimising number of patches passed to the boundary-presence classifier. We evaluate our proposed approach for a clinically relevant task of prostate gland segmentation on trans-rectal ultrasound images. We show improved performance compared to other tested weakly supervised methods, using the same labels e.g., multiple instance learning.

Zachary MC Baum, Yipeng Hu, Dean C Barratt

Neural networks have been proposed for medical image registration by learning, with a substantial amount of training data, the optimal transformations between image pairs. These trained networks can further be optimized on a single pair of test images - known as test-time optimization. This work formulates image registration as a meta-learning algorithm. Such networks can be trained by aligning the training image pairs while simultaneously improving test-time optimization efficacy; tasks which were previously considered two independent training and optimization processes. The proposed meta-registration is hypothesized to maximize the efficiency and effectiveness of the test-time optimization in the "outer" meta-optimization of the networks. For image guidance applications that often are time-critical yet limited in training data, the potentially gained speed and accuracy are compared with classical registration algorithms, registration networks without meta-learning, and single-pair optimization without test-time optimization data. Experiments are presented in this paper using clinical transrectal ultrasound image data from 108 prostate cancer patients. These experiments demonstrate the effectiveness of a meta-registration protocol, which yields significantly improved performance relative to existing learning-based methods. Furthermore, the meta-registration achieves comparable results to classical iterative methods in a fraction of the time, owing to its rapid test-time optimization process.

Zachary MC Baum, Tamas Ungi, Christopher Schlenger et al.

Free Point Transformer (FPT) has been proposed as a data-driven, non-rigid point set registration approach using deep neural networks. As FPT does not assume constraints based on point vicinity or correspondence, it may be trained simply and in a flexible manner by minimizing an unsupervised loss based on the Chamfer Distance. This makes FPT amenable to real-world medical imaging applications where ground-truth deformations may be infeasible to obtain, or in scenarios where only a varying degree of completeness in the point sets to be aligned is available. To test the limit of the correspondence finding ability of FPT and its dependency on training data sets, this work explores the generalizability of the FPT from well-curated non-medical data sets to medical imaging data sets. First, we train FPT on the ModelNet40 dataset to demonstrate its effectiveness and the superior registration performance of FPT over iterative and learning-based point set registration methods. Second, we demonstrate superior performance in rigid and non-rigid registration and robustness to missing data. Last, we highlight the interesting generalizability of the ModelNet-trained FPT by registering reconstructed freehand ultrasound scans of the spine and generic spine models without additional training, whereby the average difference to the ground truth curvatures is 1.3 degrees, across 13 patients.

Pierre Raillard, Lorenzo Cristoni, Andrew Walden et al.

Artificial intelligence-based analysis of lung ultrasound imaging has been demonstrated as an effective technique for rapid diagnostic decision support throughout the COVID-19 pandemic. However, such techniques can require days- or weeks-long training processes and hyper-parameter tuning to develop intelligent deep learning image analysis models. This work focuses on leveraging 'off-the-shelf' pre-trained models as deep feature extractors for scoring disease severity with minimal training time. We propose using pre-trained initializations of existing methods ahead of simple and compact neural networks to reduce reliance on computational capacity. This reduction of computational capacity is of critical importance in time-limited or resource-constrained circumstances, such as the early stages of a pandemic. On a dataset of 49 patients, comprising over 20,000 images, we demonstrate that the use of existing methods as feature extractors results in the effective classification of COVID-19-related pneumonia severity while requiring only minutes of training time. Our methods can achieve an accuracy of over 0.93 on a 4-level severity score scale and provides comparable per-patient region and global scores compared to expert annotated ground truths. These results demonstrate the capability for rapid deployment and use of such minimally-adapted methods for progress monitoring, patient stratification and management in clinical practice for COVID-19 patients, and potentially in other respiratory diseases.

Liam F Chalcroft, Jiongqi Qu, Sophie A Martin et al.

When developing deep neural networks for segmenting intraoperative ultrasound images, several practical issues are encountered frequently, such as the presence of ultrasound frames that do not contain regions of interest and the high variance in ground-truth labels. In this study, we evaluate the utility of a pre-screening classification network prior to the segmentation network. Experimental results demonstrate that such a classifier, minimising frame classification errors, was able to directly impact the number of false positive and false negative frames. Importantly, the segmentation accuracy on the classifier-selected frames, that would be segmented, remains comparable to or better than those from standalone segmentation networks. Interestingly, the efficacy of the pre-screening classifier was affected by the sampling methods for training labels from multiple observers, a seemingly independent problem. We show experimentally that a previously proposed approach, combining random sampling and consensus labels, may need to be adapted to perform well in our application. Furthermore, this work aims to share practical experience in developing a machine learning application that assists highly variable interventional imaging for prostate cancer patients, to present robust and reproducible open-source implementations, and to report a set of comprehensive results and analysis comparing these practical, yet important, options in a real-world clinical application.

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.

N. Montana Brown, Y. Fu, S. U. Saeed et al.

This document outlines a tutorial to get started with medical image registration using the open-source package DeepReg. The basic concepts of medical image registration are discussed, linking classical methods to newer methods using deep learning. Two iterative, classical algorithms using optimisation and one learning-based algorithm using deep learning are coded step-by-step using DeepReg utilities, all with real, open-accessible, medical data.

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.

Zachary M C Baum, Yipeng Hu, Dean C Barratt

We present Free Point Transformer (FPT) - a deep neural network architecture for non-rigid point-set registration. Consisting of two modules, a global feature extraction module and a point transformation module, FPT does not assume explicit constraints based on point vicinity, thereby overcoming a common requirement of previous learning-based point-set registration methods. FPT is designed to accept unordered and unstructured point-sets with a variable number of points and uses a "model-free" approach without heuristic constraints. Training FPT is flexible and involves minimizing an intuitive unsupervised loss function, but supervised, semi-supervised, and partially- or weakly-supervised training are also supported. This flexibility makes FPT amenable to multimodal image registration problems where the ground-truth deformations are difficult or impossible to measure. In this paper, we demonstrate the application of FPT to non-rigid registration of prostate magnetic resonance (MR) imaging and sparsely-sampled transrectal ultrasound (TRUS) images. The registration errors were 4.71 mm and 4.81 mm for complete TRUS imaging and sparsely-sampled TRUS imaging, respectively. The results indicate superior accuracy to the alternative rigid and non-rigid registration algorithms tested and substantially lower computation time. The rapid inference possible with FPT makes it particularly suitable for applications where real-time registration is beneficial.

Harry Mason, Lorenzo Cristoni, Andrew Walden et al.

Lung ultrasound imaging has been shown effective in detecting typical patterns for interstitial pneumonia, as a point-of-care tool for both patients with COVID-19 and other community-acquired pneumonia (CAP). In this work, we focus on the hyperechoic B-line segmentation task. Using deep neural networks, we automatically outline the regions that are indicative of pathology-sensitive artifacts and their associated sonographic patterns. With a real-world data-scarce scenario, we investigate approaches to utilize both COVID-19 and CAP lung ultrasound data to train the networks; comparing fine-tuning and unsupervised domain adaptation. Segmenting either type of lung condition at inference may support a range of clinical applications during evolving epidemic stages, but also demonstrates value in resource-constrained clinical scenarios. Adapting real clinical data acquired from COVID-19 patients to those from CAP patients significantly improved Dice scores from 0.60 to 0.87 (p < 0.001) and from 0.43 to 0.71 (p < 0.001), on independent COVID-19 and CAP test cases, respectively. It is of practical value that the improvement was demonstrated with only a small amount of data in both training and adaptation data sets, a common constraint for deploying machine learning models in clinical practice. Interestingly, we also report that the inverse adaptation, from labelled CAP data to unlabeled COVID-19 data, did not demonstrate an improvement when tested on either condition. Furthermore, we offer a possible explanation that correlates the segmentation performance to label consistency and data domain diversity in this point-of-care lung ultrasound application.

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.

Zachary M C Baum, Ester Bonmati, Lorenzo Cristoni et al.

We describe a novel, two-stage computer assistance system for lung anomaly detection using ultrasound imaging in the intensive care setting to improve operator performance and patient stratification during coronavirus pandemics. The proposed system consists of two deep-learning-based models: a quality assessment module that automates predictions of image quality, and a diagnosis assistance module that determines the likelihood-oh-anomaly in ultrasound images of sufficient quality. Our two-stage strategy uses a novelty detection algorithm to address the lack of control cases available for training the quality assessment classifier. The diagnosis assistance module can then be trained with data that are deemed of sufficient quality, guaranteed by the closed-loop feedback mechanism from the quality assessment module. Using more than 25000 ultrasound images from 37 COVID-19-positive patients scanned at two hospitals, plus 12 control cases, this study demonstrates the feasibility of using the proposed machine learning approach. We report an accuracy of 86% when classifying between sufficient and insufficient quality images by the quality assessment module. For data of sufficient quality - as determined by the quality assessment module - the mean classification accuracy, sensitivity, and specificity in detecting COVID-19-positive cases were 0.95, 0.91, and 0.97, respectively, across five holdout test data sets unseen during the training of any networks within the proposed system. Overall, the integration of the two modules yields accurate, fast, and practical acquisition guidance and diagnostic assistance for patients with suspected respiratory conditions at point-of-care.

Zachary M. C. Baum, Yipeng Hu, Dean C. Barratt

We describe a point-set registration algorithm based on a novel free point transformer (FPT) network, designed for points extracted from multimodal biomedical images for registration tasks, such as those frequently encountered in ultrasound-guided interventional procedures. FPT is constructed with a global feature extractor which accepts unordered source and target point-sets of variable size. The extracted features are conditioned by a shared multilayer perceptron point transformer module to predict a displacement vector for each source point, transforming it into the target space. The point transformer module assumes no vicinity or smoothness in predicting spatial transformation and, together with the global feature extractor, is trained in a data-driven fashion with an unsupervised loss function. In a multimodal registration task using prostate MR and sparsely acquired ultrasound images, FPT yields comparable or improved results over other rigid and non-rigid registration methods. This demonstrates the versatility of FPT to learn registration directly from real, clinical training data and to generalize to a challenging task, such as the interventional application presented.