Multi-Subject Image Synthesis as a Generative Prior for Single-Subject PET Image Reconstruction

Large high-quality medical image datasets are difficult to acquire but necessary for many deep learning applications. For positron emission tomography (PET), reconstructed image quality is limited by inherent Poisson noise. We propose a novel method for synthesising diverse and realistic pseudo-PET images with improved signal-to-noise ratio. We also show how our pseudo-PET images may be exploited as a generative prior for single-subject PET image reconstruction. Firstly, we perform deep-learned deformable registration of multi-subject magnetic resonance (MR) images paired to multi-subject PET images. We then use the anatomically-learned deformation fields to transform multiple PET images to the same reference space, before averaging random subsets of the transformed multi-subject data to form a large number of varying pseudo-PET images. We observe that using MR information for registration imbues the resulting pseudo-PET images with improved anatomical detail compared to the originals. We consider applications to PET image reconstruction, by generating pseudo-PET images in the same space as the intended single-subject reconstruction and using them as training data for a diffusion model-based reconstruction method. We show visual improvement and reduced background noise in our 2D reconstructions as compared to OSEM, MAP-EM and an existing state-of-the-art diffusion model-based approach. Our method shows the potential for utilising highly subject-specific prior information within a generative reconstruction framework. Future work may compare the benefits of our approach to explicitly MR-guided reconstruction methodologies.

Likelihood-Scheduled Score-Based Generative Modeling for Fully 3D PET Image Reconstruction

Medical image reconstruction with pre-trained score-based generative models (SGMs) has advantages over other existing state-of-the-art deep-learned reconstruction methods, including improved resilience to different scanner setups and advanced image distribution modeling. SGM-based reconstruction has recently been applied to simulated positron emission tomography (PET) datasets, showing improved contrast recovery for out-of-distribution lesions relative to the state-of-the-art. However, existing methods for SGM-based reconstruction from PET data suffer from slow reconstruction, burdensome hyperparameter tuning and slice inconsistency effects (in 3D). In this work, we propose a practical methodology for fully 3D reconstruction that accelerates reconstruction and reduces the number of critical hyperparameters by matching the likelihood of an SGM's reverse diffusion process to a current iterate of the maximum-likelihood expectation maximization algorithm. Using the example of low-count reconstruction from simulated $[^{18}$F]DPA-714 datasets, we show our methodology can match or improve on the NRMSE and SSIM of existing state-of-the-art SGM-based PET reconstruction while reducing reconstruction time and the need for hyperparameter tuning. We evaluate our methodology against state-of-the-art supervised and conventional reconstruction algorithms. Finally, we demonstrate a first-ever implementation of SGM-based reconstruction for real 3D PET data, specifically $[^{18}$F]DPA-714 data, where we integrate perpendicular pre-trained SGMs to eliminate slice inconsistency issues.

Generative-Model-Based Fully 3D PET Image Reconstruction by Conditional Diffusion Sampling

Score-based generative models (SGMs) have recently shown promising results for image reconstruction on simulated positron emission tomography (PET) datasets. In this work we have developed and implemented practical methodology for 3D image reconstruction with SGMs, and perform (to our knowledge) the first SGM-based reconstruction of real fully 3D PET data. We train an SGM on full-count reference brain images, and extend methodology to allow SGM-based reconstructions at very low counts (1% of original, to simulate low-dose or short-duration scanning). We then perform reconstructions for multiple independent realisations of 1% count data, allowing us to analyse the bias and variance characteristics of the method. We sample from the learned posterior distribution of the generative algorithm to calculate uncertainty images for our reconstructions. We evaluate the method's performance on real full- and low-count PET data and compare with conventional OSEM and MAP-EM baselines, showing that our SGM-based low-count reconstructions match full-dose reconstructions more closely and in a bias-variance trade-off comparison, our SGM-reconstructed images have lower variance than existing baselines. Future work will compare to supervised deep-learned methods, with other avenues for investigation including how data conditioning affects the SGM's posterior distribution and the algorithm's performance with different tracers.

DeepSPV: An Interpretable Deep Learning Pipeline for 3D Spleen Volume Estimation from 2D Ultrasound Images

Splenomegaly, the enlargement of the spleen, is an important clinical indicator for various associated medical conditions, such as sickle cell disease (SCD). Spleen length measured from 2D ultrasound is the most widely used metric for characterising spleen size. However, it is still considered a surrogate measure, and spleen volume remains the gold standard for assessing spleen size. Accurate spleen volume measurement typically requires 3D imaging modalities, such as computed tomography or magnetic resonance imaging, but these are not widely available, especially in the Global South which has a high prevalence of SCD. In this work, we introduce a deep learning pipeline, DeepSPV, for precise spleen volume estimation from single or dual 2D ultrasound images. The pipeline involves a segmentation network and a variational autoencoder for learning low-dimensional representations from the estimated segmentations. We investigate three approaches for spleen volume estimation and our best model achieves 86.62%/92.5% mean relative volume accuracy (MRVA) under single-view/dual-view settings, surpassing the performance of human experts. In addition, the pipeline can provide confidence intervals for the volume estimates as well as offering benefits in terms of interpretability, which further support clinicians in decision-making when identifying splenomegaly. We evaluate the full pipeline using a highly realistic synthetic dataset generated by a diffusion model, achieving an overall MRVA of 83.0% from a single 2D ultrasound image. Our proposed DeepSPV is the first work to use deep learning to estimate 3D spleen volume from 2D ultrasound images and can be seamlessly integrated into the current clinical workflow for spleen assessment.

Improving the Scan-rescan Precision of AI-based CMR Biomarker Estimation

Quantification of cardiac biomarkers from cine cardiovascular magnetic resonance (CMR) data using deep learning (DL) methods offers many advantages, such as increased accuracy and faster analysis. However, only a few studies have focused on the scan-rescan precision of the biomarker estimates, which is important for reproducibility and longitudinal analysis. Here, we propose a cardiac biomarker estimation pipeline that not only focuses on achieving high segmentation accuracy but also on improving the scan-rescan precision of the computed biomarkers, namely left and right ventricular ejection fraction, and left ventricular myocardial mass. We evaluate two approaches to improve the apical-basal resolution of the segmentations used for estimating the biomarkers: one based on image interpolation and one based on segmentation interpolation. Using a database comprising scan-rescan cine CMR data acquired from 92 subjects, we compare the performance of these two methods against ground truth (GT) segmentations and DL segmentations obtained before interpolation (baseline). The results demonstrate that both the image-based and segmentation-based interpolation methods were able to narrow Bland-Altman scan-rescan confidence intervals for all biomarkers compared to the GT and baseline performances. Our findings highlight the importance of focusing not only on segmentation accuracy but also on the consistency of biomarkers across repeated scans, which is crucial for longitudinal analysis of cardiac function.

An investigation into the causes of race bias in AI-based cine CMR segmentation

Artificial intelligence (AI) methods are being used increasingly for the automated segmentation of cine cardiac magnetic resonance (CMR) imaging. However, these methods have been shown to be subject to race bias, i.e. they exhibit different levels of performance for different races depending on the (im)balance of the data used to train the AI model. In this paper we investigate the source of this bias, seeking to understand its root cause(s) so that it can be effectively mitigated. We perform a series of classification and segmentation experiments on short-axis cine CMR images acquired from Black and White subjects from the UK Biobank and apply AI interpretability methods to understand the results. In the classification experiments, we found that race can be predicted with high accuracy from the images alone, but less accurately from ground truth segmentations, suggesting that the distributional shift between races, which is often the cause of AI bias, is mostly image-based rather than segmentation-based. The interpretability methods showed that most attention in the classification models was focused on non-heart regions, such as subcutaneous fat. Cropping the images tightly around the heart reduced classification accuracy to around chance level. Similarly, race can be predicted from the latent representations of a biased segmentation model, suggesting that race information is encoded in the model. Cropping images tightly around the heart reduced but did not eliminate segmentation bias. We also investigate the influence of possible confounders on the bias observed.

Improving Deep Learning Model Calibration for Cardiac Applications using Deterministic Uncertainty Networks and Uncertainty-aware Training

Improving calibration performance in deep learning (DL) classification models is important when planning the use of DL in a decision-support setting. In such a scenario, a confident wrong prediction could lead to a lack of trust and/or harm in a high-risk application. We evaluate the impact on accuracy and calibration of two types of approach that aim to improve DL classification model calibration: deterministic uncertainty methods (DUM) and uncertainty-aware training. Specifically, we test the performance of three DUMs and two uncertainty-aware training approaches as well as their combinations. To evaluate their utility, we use two realistic clinical applications from the field of cardiac imaging: artefact detection from phase contrast cardiac magnetic resonance (CMR) and disease diagnosis from the public ACDC CMR dataset. Our results indicate that both DUMs and uncertainty-aware training can improve both accuracy and calibration in both of our applications, with DUMs generally offering the best improvements. We also investigate the combination of the two approaches, resulting in a novel deterministic uncertainty-aware training approach. This provides further improvements for some combinations of DUMs and uncertainty-aware training approaches.

Label Dropout: Improved Deep Learning Echocardiography Segmentation Using Multiple Datasets With Domain Shift and Partial Labelling

Echocardiography (echo) is the first imaging modality used when assessing cardiac function. The measurement of functional biomarkers from echo relies upon the segmentation of cardiac structures and deep learning models have been proposed to automate the segmentation process. However, in order to translate these tools to widespread clinical use it is important that the segmentation models are robust to a wide variety of images (e.g. acquired from different scanners, by operators with different levels of expertise etc.). To achieve this level of robustness it is necessary that the models are trained with multiple diverse datasets. A significant challenge faced when training with multiple diverse datasets is the variation in label presence, i.e. the combined data are often partially-labelled. Adaptations of the cross entropy loss function have been proposed to deal with partially labelled data. In this paper we show that training naively with such a loss function and multiple diverse datasets can lead to a form of shortcut learning, where the model associates label presence with domain characteristics, leading to a drop in performance. To address this problem, we propose a novel label dropout scheme to break the link between domain characteristics and the presence or absence of labels. We demonstrate that label dropout improves echo segmentation Dice score by 62% and 25% on two cardiac structures when training using multiple diverse partially labelled datasets.

Multi-task learning for joint weakly-supervised segmentation and aortic arch anomaly classification in fetal cardiac MRI

Congenital Heart Disease (CHD) is a group of cardiac malformations present already during fetal life, representing the prevailing category of birth defects globally. Our aim in this study is to aid 3D fetal vessel topology visualisation in aortic arch anomalies, a group which encompasses a range of conditions with significant anatomical heterogeneity. We present a multi-task framework for automated multi-class fetal vessel segmentation from 3D black blood T2w MRI and anomaly classification. Our training data consists of binary manual segmentation masks of the cardiac vessels' region in individual subjects and fully-labelled anomaly-specific population atlases. Our framework combines deep learning label propagation using VoxelMorph with 3D Attention U-Net segmentation and DenseNet121 anomaly classification. We target 11 cardiac vessels and three distinct aortic arch anomalies, including double aortic arch, right aortic arch, and suspected coarctation of the aorta. We incorporate an anomaly classifier into our segmentation pipeline, delivering a multi-task framework with the primary motivation of correcting topological inaccuracies of the segmentation. The hypothesis is that the multi-task approach will encourage the segmenter network to learn anomaly-specific features. As a secondary motivation, an automated diagnosis tool may have the potential to enhance diagnostic confidence in a decision support setting. Our results showcase that our proposed training strategy significantly outperforms label propagation and a network trained exclusively on propagated labels. Our classifier outperforms a classifier trained exclusively on T2w volume images, with an average balanced accuracy of 0.99 (0.01) after joint training. Adding a classifier improves the anatomical and topological accuracy of all correctly classified double aortic arch subjects.

An Investigation Into Race Bias in Random Forest Models Based on Breast DCE-MRI Derived Radiomics Features

Recent research has shown that artificial intelligence (AI) models can exhibit bias in performance when trained using data that are imbalanced by protected attribute(s). Most work to date has focused on deep learning models, but classical AI techniques that make use of hand-crafted features may also be susceptible to such bias. In this paper we investigate the potential for race bias in random forest (RF) models trained using radiomics features. Our application is prediction of tumour molecular subtype from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of breast cancer patients. Our results show that radiomics features derived from DCE-MRI data do contain race-identifiable information, and that RF models can be trained to predict White and Black race from these data with 60-70% accuracy, depending on the subset of features used. Furthermore, RF models trained to predict tumour molecular subtype using race-imbalanced data seem to produce biased behaviour, exhibiting better performance on test data from the race on which they were trained.