T2-Only Prostate Cancer Prediction by Meta-Learning from Bi-Parametric MR Imaging

Current imaging-based prostate cancer diagnosis requires both MR T2-weighted (T2w) and diffusion-weighted imaging (DWI) sequences, with additional sequences for potentially greater accuracy improvement. However, measuring diffusion patterns in DWI sequences can be time-consuming, prone to artifacts and sensitive to imaging parameters. While machine learning (ML) models have demonstrated radiologist-level accuracy in detecting prostate cancer from these two sequences, this study investigates the potential of ML-enabled methods using only the T2w sequence as input during inference time. We first discuss the technical feasibility of such a T2-only approach, and then propose a novel ML formulation, where DWI sequences - readily available for training purposes - are only used to train a meta-learning model, which subsequently only uses T2w sequences at inference. Using multiple datasets from more than 3,000 prostate cancer patients, we report superior or comparable performance in localising radiologist-identified prostate cancer using our proposed T2-only models, compared with alternative models using T2-only or both sequences as input. Real patient cases are presented and discussed to demonstrate, for the first time, the exclusively true-positive cases from models with different input sequences.

Nonrigid Reconstruction of Freehand Ultrasound without a Tracker

Reconstructing 2D freehand Ultrasound (US) frames into 3D space without using a tracker has recently seen advances with deep learning. Predicting good frame-to-frame rigid transformations is often accepted as the learning objective, especially when the ground-truth labels from spatial tracking devices are inherently rigid transformations. Motivated by a) the observed nonrigid deformation due to soft tissue motion during scanning, and b) the highly sensitive prediction of rigid transformation, this study investigates the methods and their benefits in predicting nonrigid transformations for reconstructing 3D US. We propose a novel co-optimisation algorithm for simultaneously estimating rigid transformations among US frames, supervised by ground-truth from a tracker, and a nonrigid deformation, optimised by a regularised registration network. We show that these two objectives can be either optimised using meta-learning or combined by weighting. A fast scattered data interpolation is also developed for enabling frequent reconstruction and registration of non-parallel US frames, during training. With a new data set containing over 357,000 frames in 720 scans, acquired from 60 subjects, the experiments demonstrate that, due to an expanded thus easier-to-optimise solution space, the generalisation is improved with the added deformation estimation, with respect to the rigid ground-truth. The global pixel reconstruction error (assessing accumulative prediction) is lowered from 18.48 to 16.51 mm, compared with baseline rigid-transformation-predicting methods. Using manually identified landmarks, the proposed co-optimisation also shows potentials in compensating nonrigid tissue motion at inference, which is not measurable by tracker-provided ground-truth. The code and data used in this paper are made publicly available at https://github.com/QiLi111/NR-Rec-FUS.

Biomechanics-informed Non-rigid Medical Image Registration and its Inverse Material Property Estimation with Linear and Nonlinear Elasticity

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.

Competing for pixels: a self-play algorithm for weakly-supervised segmentation

Weakly-supervised segmentation (WSS) methods, reliant on image-level labels indicating object presence, lack explicit correspondence between labels and regions of interest (ROIs), posing a significant challenge. Despite this, WSS methods have attracted attention due to their much lower annotation costs compared to fully-supervised segmentation. Leveraging reinforcement learning (RL) self-play, we propose a novel WSS method that gamifies image segmentation of a ROI. We formulate segmentation as a competition between two agents that compete to select ROI-containing patches until exhaustion of all such patches. The score at each time-step, used to compute the reward for agent training, represents likelihood of object presence within the selection, determined by an object presence detector pre-trained using only image-level binary classification labels of object presence. Additionally, we propose a game termination condition that can be called by either side upon exhaustion of all ROI-containing patches, followed by the selection of a final patch from each. Upon termination, the agent is incentivised if ROI-containing patches are exhausted or disincentivised if an ROI-containing patch is found by the competitor. This competitive setup ensures minimisation of over- or under-segmentation, a common problem with WSS methods. Extensive experimentation across four datasets demonstrates significant performance improvements over recent state-of-the-art methods. Code: https://github.com/s-sd/spurl/tree/main/wss

Weakly supervised localisation of prostate cancer using reinforcement learning for bi-parametric MR images

In this paper we propose a reinforcement learning based weakly supervised system for localisation. We train a controller function to localise regions of interest within an image by introducing a novel reward definition that utilises non-binarised classification probability, generated by a pre-trained binary classifier which classifies object presence in images or image crops. The object-presence classifier may then inform the controller of its localisation quality by quantifying the likelihood of the image containing an object. Such an approach allows us to minimize any potential labelling or human bias propagated via human labelling for fully supervised localisation. We evaluate our proposed approach for a task of cancerous lesion localisation on a large dataset of real clinical bi-parametric MR images of the prostate. Comparisons to the commonly used multiple-instance learning weakly supervised localisation and to a fully supervised baseline show that our proposed method outperforms the multi-instance learning and performs comparably to fully-supervised learning, using only image-level classification labels for training.

Semi-weakly-supervised neural network training for medical image registration

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.

Long-term Dependency for 3D Reconstruction of Freehand Ultrasound Without External Tracker

Objective: Reconstructing freehand ultrasound in 3D without any external tracker has been a long-standing challenge in ultrasound-assisted procedures. We aim to define new ways of parameterising long-term dependencies, and evaluate the performance. Methods: First, long-term dependency is encoded by transformation positions within a frame sequence. This is achieved by combining a sequence model with a multi-transformation prediction. Second, two dependency factors are proposed, anatomical image content and scanning protocol, for contributing towards accurate reconstruction. Each factor is quantified experimentally by reducing respective training variances. Results: 1) The added long-term dependency up to 400 frames at 20 frames per second (fps) indeed improved reconstruction, with an up to 82.4% lowered accumulated error, compared with the baseline performance. The improvement was found to be dependent on sequence length, transformation interval and scanning protocol and, unexpectedly, not on the use of recurrent networks with long-short term modules; 2) Decreasing either anatomical or protocol variance in training led to poorer reconstruction accuracy. Interestingly, greater performance was gained from representative protocol patterns, than from representative anatomical features. Conclusion: The proposed algorithm uses hyperparameter tuning to effectively utilise long-term dependency. The proposed dependency factors are of practical significance in collecting diverse training data, regulating scanning protocols and developing efficient networks. Significance: The proposed new methodology with publicly available volunteer data and code for parametersing the long-term dependency, experimentally shown to be valid sources of performance improvement, which could potentially lead to better model development and practical optimisation of the reconstruction application.

Boundary-RL: Reinforcement Learning for Weakly-Supervised Prostate Segmentation in TRUS Images

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.

Privileged Anatomical and Protocol Discrimination in Trackerless 3D Ultrasound Reconstruction

Three-dimensional (3D) freehand ultrasound (US) reconstruction without using any additional external tracking device has seen recent advances with deep neural networks (DNNs). In this paper, we first investigated two identified contributing factors of the learned inter-frame correlation that enable the DNN-based reconstruction: anatomy and protocol. We propose to incorporate the ability to represent these two factors - readily available during training - as the privileged information to improve existing DNN-based methods. This is implemented in a new multi-task method, where the anatomical and protocol discrimination are used as auxiliary tasks. We further develop a differentiable network architecture to optimise the branching location of these auxiliary tasks, which controls the ratio between shared and task-specific network parameters, for maximising the benefits from the two auxiliary tasks. Experimental results, on a dataset with 38 forearms of 19 volunteers acquired with 6 different scanning protocols, show that 1) both anatomical and protocol variances are enabling factors for DNN-based US reconstruction; 2) learning how to discriminate different subjects (anatomical variance) and predefined types of scanning paths (protocol variance) both significantly improve frame prediction accuracy, volume reconstruction overlap, accumulated tracking error and final drift, using the proposed algorithm.

Combiner and HyperCombiner Networks: Rules to Combine Multimodality MR Images for Prostate Cancer Localisation

One of the distinct characteristics in radiologists' reading of multiparametric prostate MR scans, using reporting systems such as PI-RADS v2.1, is to score individual types of MR modalities, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced, and then combine these image-modality-specific scores using standardised decision rules to predict the likelihood of clinically significant cancer. This work aims to demonstrate that it is feasible for low-dimensional parametric models to model such decision rules in the proposed Combiner networks, without compromising the accuracy of predicting radiologic labels: First, it is shown that either a linear mixture model or a nonlinear stacking model is sufficient to model PI-RADS decision rules for localising prostate cancer. Second, parameters of these (generalised) linear models are proposed as hyperparameters, to weigh multiple networks that independently represent individual image modalities in the Combiner network training, as opposed to end-to-end modality ensemble. A HyperCombiner network is developed to train a single image segmentation network that can be conditioned on these hyperparameters during inference, for much improved efficiency. Experimental results based on data from 850 patients, for the application of automating radiologist labelling multi-parametric MR, compare the proposed combiner networks with other commonly-adopted end-to-end networks. Using the added advantages of obtaining and interpreting the modality combining rules, in terms of the linear weights or odds-ratios on individual image modalities, three clinical applications are presented for prostate cancer segmentation, including modality availability assessment, importance quantification and rule discovery.