Segmentation by registration-enabled SAM prompt engineering using five reference images

The recently proposed Segment Anything Model (SAM) is a general tool for image segmentation, but it requires additional adaptation and careful fine-tuning for medical image segmentation, especially for small, irregularly-shaped, and boundary-ambiguous anatomical structures such as the knee cartilage that is of interest in this work. Repaired cartilage, after certain surgical procedures, exhibits imaging patterns unseen to pre-training, posing further challenges for using models like SAM with or without general-purpose fine-tuning. To address this, we propose a novel registration-based prompt engineering framework for medical image segmentation using SAM. This approach utilises established image registration algorithms to align the new image (to-be-segmented) and a small number of reference images, without requiring segmentation labels. The spatial transformations generated by registration align either the new image or pre-defined point-based prompts, before using them as input to SAM. This strategy, requiring as few as five reference images with defined point prompts, effectively prompts SAM for inference on new images, without needing any segmentation labels. Evaluation of MR images from patients who received cartilage stem cell therapy yielded Dice scores of 0.89, 0.87, 0.53, and 0.52 for segmenting femur, tibia, femoral- and tibial cartilages, respectively. This outperforms atlas-based label fusion and is comparable to supervised nnUNet, an upper-bound fair baseline in this application, both of which require full segmentation labels for reference samples. The codes are available at: https://github.com/chrissyinreallife/KneeSegmentWithSAM.git

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.

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.

Importance of Aligning Training Strategy with Evaluation for Diffusion Models in 3D Multiclass Segmentation

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, for the first time, DDPMs are used for 3D multiclass image segmentation. We make three key contributions that all focus on aligning the training strategy with the evaluation methodology, and improving efficiency. Firstly, the model predicts segmentation masks instead of sampled noise and is optimised directly via Dice loss. Secondly, the predicted mask in the previous time step is recycled to generate noise-corrupted masks to reduce information leakage. Finally, the diffusion process during training was reduced to five steps, the same as the evaluation. Through studies on two large multiclass data sets (prostate MR and abdominal CT), we demonstrated significantly improved performance compared to existing DDPMs, and reached competitive performance with non-diffusion segmentation models, based on U-net, within the same compute budget. The JAX-based diffusion framework has been released on https://github.com/mathpluscode/ImgX-DiffSeg.

Bi-parametric prostate MR image synthesis using pathology and sequence-conditioned stable diffusion

We propose an image synthesis mechanism for multi-sequence prostate MR images conditioned on text, to control lesion presence and sequence, as well as to generate paired bi-parametric images conditioned on images e.g. for generating diffusion-weighted MR from T2-weighted MR for paired data, which are two challenging tasks in pathological image synthesis. Our proposed mechanism utilises and builds upon the recent stable diffusion model by proposing image-based conditioning for paired data generation. We validate our method using 2D image slices from real suspected prostate cancer patients. The realism of the synthesised images is validated by means of a blind expert evaluation for identifying real versus fake images, where a radiologist with 4 years experience reading urological MR only achieves 59.4% accuracy across all tested sequences (where chance is 50%). For the first time, we evaluate the realism of the generated pathology by blind expert identification of the presence of suspected lesions, where we find that the clinician performs similarly for both real and synthesised images, with a 2.9 percentage point difference in lesion identification accuracy between real and synthesised images, demonstrating the potentials in radiological training purposes. Furthermore, we also show that a machine learning model, trained for lesion identification, shows better performance (76.2% vs 70.4%, statistically significant improvement) when trained with real data augmented by synthesised data as opposed to training with only real images, demonstrating usefulness for model training.

Non-rigid Medical Image Registration using Physics-informed Neural Networks

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.

Active learning using adaptable task-based prioritisation

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.