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.

AI-assisted prostate cancer detection and localisation on biparametric MR by classifying radiologist-positives

Prostate cancer diagnosis through MR imaging have currently relied on radiologists' interpretation, whilst modern AI-based methods have been developed to detect clinically significant cancers independent of radiologists. In this study, we propose to develop deep learning models that improve the overall cancer diagnostic accuracy, by classifying radiologist-identified patients or lesions (i.e. radiologist-positives), as opposed to the existing models that are trained to discriminate over all patients. We develop a single voxel-level classification model, with a simple percentage threshold to determine positive cases, at levels of lesions, Barzell-zones and patients. Based on the presented experiments from two clinical data sets, consisting of histopathology-labelled MR images from more than 800 and 500 patients in the respective UCLA and UCL PROMIS studies, we show that the proposed strategy can improve the diagnostic accuracy, by augmenting the radiologist reading of the MR imaging. Among varying definition of clinical significance, the proposed strategy, for example, achieved a specificity of 44.1% (with AI assistance) from 36.3% (by radiologists alone), at a controlled sensitivity of 80.0% on the publicly available UCLA data set. This provides measurable clinical values in a range of applications such as reducing unnecessary biopsies, lowering cost in cancer screening and quantifying risk in therapies.

Poisson Ordinal Network for Gleason Group Estimation Using Bi-Parametric MRI

The Gleason groups serve as the primary histological grading system for prostate cancer, providing crucial insights into the cancer's potential for growth and metastasis. In clinical practice, pathologists determine the Gleason groups based on specimens obtained from ultrasound-guided biopsies. In this study, we investigate the feasibility of directly estimating the Gleason groups from MRI scans to reduce otherwise required biopsies. We identify two characteristics of this task, ordinality and the resulting dependent yet unknown variances between Gleason groups. In addition to the inter- / intra- observer variability in a multi-step Gleason scoring process based on the interpretation of Gleason patterns, our MR-based prediction is also subject to specimen sampling variance and, to a lesser degree, varying MR imaging protocols. To address this challenge, we propose a novel Poisson ordinal network (PON). PONs model the prediction using a Poisson distribution and leverages Poisson encoding and Poisson focal loss to capture a learnable dependency between ordinal classes (here, Gleason groups), rather than relying solely on the numerical ground-truth (e.g. Gleason Groups 1-5 or Gleason Scores 6-10). To improve this modelling efficacy, PONs also employ contrastive learning with a memory bank to regularise intra-class variance, decoupling the memory requirement of contrast learning from the batch size. Experimental results based on the images labelled by saturation biopsies from 265 prior-biopsy-blind patients, across two tasks demonstrate the superiority and effectiveness of our proposed method.

ssVERDICT: Self-Supervised VERDICT-MRI for Enhanced Prostate Tumour Characterisation

Purpose: Demonstrating and assessing self-supervised machine learning fitting of the VERDICT (Vascular, Extracellular and Restricted DIffusion for Cytometry in Tumours) model for prostate. Methods: We derive a self-supervised neural network for fitting VERDICT (ssVERDICT) that estimates parameter maps without training data. We compare the performance of ssVERDICT to two established baseline methods for fitting diffusion MRI models: conventional nonlinear least squares (NLLS) and supervised deep learning. We do this quantitatively on simulated data, by comparing the Pearson's correlation coefficient, mean-squared error (MSE), bias, and variance with respect to the simulated ground truth. We also calculate in vivo parameter maps on a cohort of 20 prostate cancer patients and compare the methods' performance in discriminating benign from cancerous tissue via Wilcoxon's signed-rank test. Results: In simulations, ssVERDICT outperforms the baseline methods (NLLS and supervised DL) in estimating all the parameters from the VERDICT prostate model in terms of Pearson's correlation coefficient, bias, and MSE. In vivo, ssVERDICT shows stronger lesion conspicuity across all parameter maps, and improves discrimination between benign and cancerous tissue over the baseline methods. Conclusion: ssVERDICT significantly outperforms state-of-the-art methods for VERDICT model fitting, and shows for the first time, fitting of a complex three-compartment biophysical model with machine learning without the requirement of explicit training labels.

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.

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.

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.

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.

Unsupervised Domain Adaptation with Semantic Consistency across Heterogeneous Modalities for MRI Prostate Lesion Segmentation

Any novel medical imaging modality that differs from previous protocols e.g. in the number of imaging channels, introduces a new domain that is heterogeneous from previous ones. This common medical imaging scenario is rarely considered in the domain adaptation literature, which handles shifts across domains of the same dimensionality. In our work we rely on stochastic generative modeling to translate across two heterogeneous domains at pixel space and introduce two new loss functions that promote semantic consistency. Firstly, we introduce a semantic cycle-consistency loss in the source domain to ensure that the translation preserves the semantics. Secondly, we introduce a pseudo-labelling loss, where we translate target data to source, label them by a source-domain network, and use the generated pseudo-labels to supervise the target-domain network. Our results show that this allows us to extract systematically better representations for the target domain. In particular, we address the challenge of enhancing performance on VERDICT-MRI, an advanced diffusion-weighted imaging technique, by exploiting labeled mp-MRI data. When compared to several unsupervised domain adaptation approaches, our approach yields substantial improvements, that consistently carry over to the semi-supervised and supervised learning settings.

Harnessing Uncertainty in Domain Adaptation for MRI Prostate Lesion Segmentation

The need for training data can impede the adoption of novel imaging modalities for learning-based medical image analysis. Domain adaptation methods partially mitigate this problem by translating training data from a related source domain to a novel target domain, but typically assume that a one-to-one translation is possible. Our work addresses the challenge of adapting to a more informative target domain where multiple target samples can emerge from a single source sample. In particular we consider translating from mp-MRI to VERDICT, a richer MRI modality involving an optimized acquisition protocol for cancer characterization. We explicitly account for the inherent uncertainty of this mapping and exploit it to generate multiple outputs conditioned on a single input. Our results show that this allows us to extract systematically better image representations for the target domain, when used in tandem with both simple, CycleGAN-based baselines, as well as more powerful approaches that integrate discriminative segmentation losses and/or residual adapters. When compared to its deterministic counterparts, our approach yields substantial improvements across a broad range of dataset sizes, increasingly strong baselines, and evaluation measures.