Domain Generalization for Prostate Segmentation in Transrectal Ultrasound Images: A Multi-center Study

Prostate biopsy and image-guided treatment procedures are often performed under the guidance of ultrasound fused with magnetic resonance images (MRI). Accurate image fusion relies on accurate segmentation of the prostate on ultrasound images. Yet, the reduced signal-to-noise ratio and artifacts (e.g., speckle and shadowing) in ultrasound images limit the performance of automated prostate segmentation techniques and generalizing these methods to new image domains is inherently difficult. In this study, we address these challenges by introducing a novel 2.5D deep neural network for prostate segmentation on ultrasound images. Our approach addresses the limitations of transfer learning and finetuning methods (i.e., drop in performance on the original training data when the model weights are updated) by combining a supervised domain adaptation technique and a knowledge distillation loss. The knowledge distillation loss allows the preservation of previously learned knowledge and reduces the performance drop after model finetuning on new datasets. Furthermore, our approach relies on an attention module that considers model feature positioning information to improve the segmentation accuracy. We trained our model on 764 subjects from one institution and finetuned our model using only ten subjects from subsequent institutions. We analyzed the performance of our method on three large datasets encompassing 2067 subjects from three different institutions. Our method achieved an average Dice Similarity Coefficient (Dice) of $94.0\pm0.03$ and Hausdorff Distance (HD95) of 2.28 $mm$ in an independent set of subjects from the first institution. Moreover, our model generalized well in the studies from the other two institutions (Dice: $91.0\pm0.03$; HD95: 3.7$mm$ and Dice: $82.0\pm0.03$; HD95: 7.1 $mm$).

Optimising Chest X-Rays for Image Analysis by Identifying and Removing Confounding Factors

During the COVID-19 pandemic, the sheer volume of imaging performed in an emergency setting for COVID-19 diagnosis has resulted in a wide variability of clinical CXR acquisitions. This variation is seen in the CXR projections used, image annotations added and in the inspiratory effort and degree of rotation of clinical images. The image analysis community has attempted to ease the burden on overstretched radiology departments during the pandemic by developing automated COVID-19 diagnostic algorithms, the input for which has been CXR imaging. Large publicly available CXR datasets have been leveraged to improve deep learning algorithms for COVID-19 diagnosis. Yet the variable quality of clinically-acquired CXRs within publicly available datasets could have a profound effect on algorithm performance. COVID-19 diagnosis may be inferred by an algorithm from non-anatomical features on an image such as image labels. These imaging shortcuts may be dataset-specific and limit the generalisability of AI systems. Understanding and correcting key potential biases in CXR images is therefore an essential first step prior to CXR image analysis. In this study, we propose a simple and effective step-wise approach to pre-processing a COVID-19 chest X-ray dataset to remove undesired biases. We perform ablation studies to show the impact of each individual step. The results suggest that using our proposed pipeline could increase accuracy of the baseline COVID-19 detection algorithm by up to 13%.

Bayesian Pseudo Labels: Expectation Maximization for Robust and Efficient Semi-Supervised Segmentation

This paper concerns pseudo labelling in segmentation. Our contribution is fourfold. Firstly, we present a new formulation of pseudo-labelling as an Expectation-Maximization (EM) algorithm for clear statistical interpretation. Secondly, we propose a semi-supervised medical image segmentation method purely based on the original pseudo labelling, namely SegPL. We demonstrate SegPL is a competitive approach against state-of-the-art consistency regularisation based methods on semi-supervised segmentation on a 2D multi-class MRI brain tumour segmentation task and a 3D binary CT lung vessel segmentation task. The simplicity of SegPL allows less computational cost comparing to prior methods. Thirdly, we demonstrate that the effectiveness of SegPL may originate from its robustness against out-of-distribution noises and adversarial attacks. Lastly, under the EM framework, we introduce a probabilistic generalisation of SegPL via variational inference, which learns a dynamic threshold for pseudo labelling during the training. We show that SegPL with variational inference can perform uncertainty estimation on par with the gold-standard method Deep Ensemble.

Cross-Modality Image Registration using a Training-Time Privileged Third Modality

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.

Rapid Lung Ultrasound COVID-19 Severity Scoring with Resource-Efficient Deep Feature Extraction

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.

Meta-Registration: Learning Test-Time Optimization for Single-Pair Image Registration

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.

Learning Generalized Non-Rigid Multimodal Biomedical Image Registration from Generic Point Set Data

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.

Strategising template-guided needle placement for MR-targeted prostate biopsy

Clinically significant prostate cancer has a better chance to be sampled during ultrasound-guided biopsy procedures, if suspected lesions found in pre-operative magnetic resonance (MR) images are used as targets. However, the diagnostic accuracy of the biopsy procedure is limited by the operator-dependent skills and experience in sampling the targets, a sequential decision making process that involves navigating an ultrasound probe and placing a series of sampling needles for potentially multiple targets. This work aims to learn a reinforcement learning (RL) policy that optimises the actions of continuous positioning of 2D ultrasound views and biopsy needles with respect to a guiding template, such that the MR targets can be sampled efficiently and sufficiently. We first formulate the task as a Markov decision process (MDP) and construct an environment that allows the targeting actions to be performed virtually for individual patients, based on their anatomy and lesions derived from MR images. A patient-specific policy can thus be optimised, before each biopsy procedure, by rewarding positive sampling in the MDP environment. Experiment results from fifty four prostate cancer patients show that the proposed RL-learned policies obtained a mean hit rate of 93% and an average cancer core length of 11 mm, which compared favourably to two alternative baseline strategies designed by humans, without hand-engineered rewards that directly maximise these clinically relevant metrics. Perhaps more interestingly, it is found that the RL agents learned strategies that were adaptive to the lesion size, where spread of the needles was prioritised for smaller lesions. Such a strategy has not been previously reported or commonly adopted in clinical practice, but led to an overall superior targeting performance when compared with intuitively designed strategies.

Collaborative Quantization Embeddings for Intra-Subject Prostate MR Image Registration

Image registration is useful for quantifying morphological changes in longitudinal MR images from prostate cancer patients. This paper describes a development in improving the learning-based registration algorithms, for this challenging clinical application often with highly variable yet limited training data. First, we report that the latent space can be clustered into a much lower dimensional space than that commonly found as bottleneck features at the deep layer of a trained registration network. Based on this observation, we propose a hierarchical quantization method, discretizing the learned feature vectors using a jointly-trained dictionary with a constrained size, in order to improve the generalisation of the registration networks. Furthermore, a novel collaborative dictionary is independently optimised to incorporate additional prior information, such as the segmentation of the gland or other regions of interest, in the latent quantized space. Based on 216 real clinical images from 86 prostate cancer patients, we show the efficacy of both the designed components. Improved registration accuracy was obtained with statistical significance, in terms of both Dice on gland and target registration error on corresponding landmarks, the latter of which achieved 5.46 mm, an improvement of 28.7\% from the baseline without quantization. Experimental results also show that the difference in performance was indeed minimised between training and testing data.

The impact of using voxel-level segmentation metrics on evaluating multifocal prostate cancer localisation

Dice similarity coefficient (DSC) and Hausdorff distance (HD) are widely used for evaluating medical image segmentation. They have also been criticised, when reported alone, for their unclear or even misleading clinical interpretation. DSCs may also differ substantially from HDs, due to boundary smoothness or multiple regions of interest (ROIs) within a subject. More importantly, either metric can also have a nonlinear, non-monotonic relationship with outcomes based on Type 1 and 2 errors, designed for specific clinical decisions that use the resulting segmentation. Whilst cases causing disagreement between these metrics are not difficult to postulate. This work first proposes a new asymmetric detection metric, adapting those used in object detection, for planning prostate cancer procedures. The lesion-level metrics is then compared with the voxel-level DSC and HD, whereas a 3D UNet is used for segmenting lesions from multiparametric MR (mpMR) images. Based on experimental results we report pairwise agreement and correlation 1) between DSC and HD, and 2) between voxel-level DSC and recall-controlled precision at lesion-level, with Cohen's [0.49, 0.61] and Pearson's [0.66, 0.76] (p-values}<0.001) at varying cut-offs. However, the differences in false-positives and false-negatives, between the actual errors and the perceived counterparts if DSC is used, can be as high as 152 and 154, respectively, out of the 357 test set lesions. We therefore carefully conclude that, despite of the significant correlations, voxel-level metrics such as DSC can misrepresent lesion-level detection accuracy for evaluating localisation of multifocal prostate cancer and should be interpreted with caution.