Joanna M. Wardlaw

Alessandro Fontanella, Grant Mair, Joanna Wardlaw et al.

Segmentation masks of pathological areas are useful in many medical applications, such as brain tumour and stroke management. Moreover, healthy counterfactuals of diseased images can be used to enhance radiologists' training files and to improve the interpretability of segmentation models. In this work, we present a weakly supervised method to generate a healthy version of a diseased image and then use it to obtain a pixel-wise anomaly map. To do so, we start by considering a saliency map that approximately covers the pathological areas, obtained with ACAT. Then, we propose a technique that allows to perform targeted modifications to these regions, while preserving the rest of the image. In particular, we employ a diffusion model trained on healthy samples and combine Denoising Diffusion Probabilistic Model (DDPM) and Denoising Diffusion Implicit Model (DDIM) at each step of the sampling process. DDPM is used to modify the areas affected by a lesion within the saliency map, while DDIM guarantees reconstruction of the normal anatomy outside of it. The two parts are also fused at each timestep, to guarantee the generation of a sample with a coherent appearance and a seamless transition between edited and unedited parts. We verify that when our method is applied to healthy samples, the input images are reconstructed without significant modifications. We compare our approach with alternative weakly supervised methods on the task of brain lesion segmentation, achieving the highest mean Dice and IoU scores among the models considered.

Alessandro Fontanella, Antreas Antoniou, Wenwen Li et al.

In some medical imaging tasks and other settings where only small parts of the image are informative for the classification task, traditional CNNs can sometimes struggle to generalise. Manually annotated Regions of Interest (ROI) are sometimes used to isolate the most informative parts of the image. However, these are expensive to collect and may vary significantly across annotators. To overcome these issues, we propose a framework that employs saliency maps to obtain soft spatial attention masks that modulate the image features at different scales. We refer to our method as Adversarial Counterfactual Attention (ACAT). ACAT increases the baseline classification accuracy of lesions in brain CT scans from 71.39% to 72.55% and of COVID-19 related findings in lung CT scans from 67.71% to 70.84% and exceeds the performance of competing methods. We investigate the best way to generate the saliency maps employed in our architecture and propose a way to obtain them from adversarially generated counterfactual images. They are able to isolate the area of interest in brain and lung CT scans without using any manual annotations. In the task of localising the lesion location out of 6 possible regions, they obtain a score of 65.05% on brain CT scans, improving the score of 61.29% obtained with the best competing method.

Alessandro Fontanella, Wenwen Li, Grant Mair et al.

Computed Tomography (CT) is commonly used to image acute ischemic stroke (AIS) patients, but its interpretation by radiologists is time-consuming and subject to inter-observer variability. Deep learning (DL) techniques can provide automated CT brain scan assessment, but usually require annotated images. Aiming to develop a DL method for AIS using labelled but not annotated CT brain scans from patients with AIS, we designed a convolutional neural network-based DL algorithm using routinely-collected CT brain scans from the Third International Stroke Trial (IST-3), which were not acquired using strict research protocols. The DL model aimed to detect AIS lesions and classify the side of the brain affected. We explored the impact of AIS lesion features, background brain appearances, and timing on DL performance. From 5772 unique CT scans of 2347 AIS patients (median age 82), 54% had visible AIS lesions according to expert labelling. Our best-performing DL method achieved 72% accuracy for lesion presence and side. Lesions that were larger (80% accuracy) or multiple (87% accuracy for two lesions, 100% for three or more), were better detected. Follow-up scans had 76% accuracy, while baseline scans 67% accuracy. Chronic brain conditions reduced accuracy, particularly non-stroke lesions and old stroke lesions (32% and 31% error rates respectively). DL methods can be designed for AIS lesion detection on CT using the vast quantities of routinely-collected CT brain scan data. Ultimately, this should lead to more robust and widely-applicable methods.

Benjamin Jin, Grant Mair, Joanna M. Wardlaw et al.

Vision Transformers (ViTs) have gained significant popularity in the natural image domain but have been less successful in 3D medical image segmentation. Nevertheless, 3D ViTs are particularly interesting for large medical imaging volumes due to their efficient self-supervised training within the masked autoencoder (MAE) framework, which enables the use of imaging data without the need for expensive manual annotations. Intracranial arterial calcification (IAC) is an imaging biomarker visible on routinely acquired CT scans linked to neurovascular diseases such as stroke and dementia, and automated IAC quantification could enable their large-scale risk assessment. We pre-train ViTs with MAE and fine-tune them for IAC segmentation for the first time. To develop our models, we use highly heterogeneous data from a large clinical trial, the third International Stroke Trial (IST-3). We evaluate key aspects of MAE pre-trained ViTs in IAC segmentation, and analyse the clinical implications. We show: 1) our calibrated self-supervised ViT beats a strong supervised nnU-Net baseline by 3.2 Dice points, 2) low patch sizes are crucial for ViTs for IAC segmentation and interpolation upsampling with regular convolutions is preferable to transposed convolutions for ViT-based models, and 3) our ViTs increase robustness to higher slice thicknesses and improve risk group classification in a clinical scenario by 46%. Our code is available online.

Jesse Phitidis, Alison Q. O'Neil, William N. Whiteley et al.

Cerebrovascular diseases (CVD) can lead to stroke and dementia. Stroke is the second leading cause of death world wide and dementia incidence is increasing by the year. There are several markers of CVD that are visible on brain imaging, including: white matter hyperintensities (WMH), acute and chronic ischaemic stroke lesions (ISL), lacunes, enlarged perivascular spaces (PVS), acute and chronic haemorrhagic lesions, and cerebral microbleeds (CMB). Brain atrophy also occurs in CVD. These markers are important for patient management and intervention, since they indicate elevated risk of future stroke and dementia. We systematically reviewed automated systems designed to support radiologists reporting on these CVD imaging findings. We considered commercially available software and research publications which identify at least two CVD markers. In total, we included 29 commercial products and 13 research publications. Two distinct types of commercial support system were available: those which identify acute stroke lesions (haemorrhagic and ischaemic) from computed tomography (CT) scans, mainly for the purpose of patient triage; and those which measure WMH and atrophy regionally and longitudinally. In research, WMH and ISL were the markers most frequently analysed together, from magnetic resonance imaging (MRI) scans; lacunes and PVS were each targeted only twice and CMB only once. For stroke, commercially available systems largely support the emergency setting, whilst research systems consider also follow-up and routine scans. The systems to quantify WMH and atrophy are focused on neurodegenerative disease support, where these CVD markers are also of significance. There are currently no openly validated systems, commercially, or in research, performing a comprehensive joint analysis of all CVD markers (WMH, ISL, lacunes, PVS, haemorrhagic lesions, CMB, and atrophy).

Ben Philps, Maria del C. Valdes Hernandez, Chen Qin et al.

White Matter Hyperintensities (WMH) are key neuroradiological markers of small vessel disease present in brain MRI. Assessment of WMH is important in research and clinics. However, WMH are challenging to segment due to their high variability in shape, location, size, poorly defined borders, and similar intensity profile to other pathologies (e.g stroke lesions) and artefacts (e.g head motion). In this work, we assess the utility and semantic properties of the most effective techniques for uncertainty quantification (UQ) in segmentation for the WMH segmentation task across multiple test-time data distributions. We find UQ techniques reduce 'silent failure' by identifying in UQ maps small WMH clusters in the deep white matter that are unsegmented by the model. A combination of Stochastic Segmentation Networks with Deep Ensembles also yields the highest Dice and lowest Absolute Volume Difference % (AVD) score and can highlight areas where there is ambiguity between WMH and stroke lesions. We further demonstrate the downstream utility of UQ, proposing a novel method for classification of the clinical Fazekas score using spatial features extracted from voxelwise WMH probability and UQ maps. We show that incorporating WMH uncertainty information improves Fazekas classification performance and calibration. Our model with (UQ and spatial WMH features)/(spatial WMH features)/(WMH volume only) achieves a balanced accuracy score of 0.74/0.67/0.62, and root brier score of 0.65/0.72/0.74 in the Deep WMH and balanced accuracy of 0.74/0.73/0.71 and root brier score of 0.64/0.66/0.68 in the Periventricular region. We further demonstrate that stochastic UQ techniques with high sample diversity can improve the detection of poor quality segmentations.

Christopher Bowles, Liang Chen, Ricardo Guerrero et al.

One of the biggest issues facing the use of machine learning in medical imaging is the lack of availability of large, labelled datasets. The annotation of medical images is not only expensive and time consuming but also highly dependent on the availability of expert observers. The limited amount of training data can inhibit the performance of supervised machine learning algorithms which often need very large quantities of data on which to train to avoid overfitting. So far, much effort has been directed at extracting as much information as possible from what data is available. Generative Adversarial Networks (GANs) offer a novel way to unlock additional information from a dataset by generating synthetic samples with the appearance of real images. This paper demonstrates the feasibility of introducing GAN derived synthetic data to the training datasets in two brain segmentation tasks, leading to improvements in Dice Similarity Coefficient (DSC) of between 1 and 5 percentage points under different conditions, with the strongest effects seen fewer than ten training image stacks are available.

Cagdas Ulas, Giles Tetteh, Michael J. Thrippleton et al.

Dynamic contrast-enhanced (DCE) MRI is an evolving imaging technique that provides a quantitative measure of pharmacokinetic (PK) parameters in body tissues, in which series of T1-weighted images are collected following the administration of a paramagnetic contrast agent. Unfortunately, in many applications, conventional clinical DCE-MRI suffers from low spatiotemporal resolution and insufficient volume coverage. In this paper, we propose a novel deep learning based approach to directly estimate the PK parameters from undersampled DCE-MRI data. Specifically, we design a custom loss function where we incorporate a forward physical model that relates the PK parameters to corrupted image-time series obtained due to subsampling in k-space. This allows the network to directly exploit the knowledge of true contrast agent kinetics in the training phase, and hence provide more accurate restoration of PK parameters. Experiments on clinical brain DCE datasets demonstrate the efficacy of our approach in terms of fidelity of PK parameter reconstruction and significantly faster parameter inference compared to a model-based iterative reconstruction method.

Enrico Pellegrini, Lucia Ballerini, Maria del C. Valdes Hernandez et al.

INTRODUCTION: Advanced machine learning methods might help to identify dementia risk from neuroimaging, but their accuracy to date is unclear. METHODS: We systematically reviewed the literature, 2006 to late 2016, for machine learning studies differentiating healthy ageing through to dementia of various types, assessing study quality, and comparing accuracy at different disease boundaries. RESULTS: Of 111 relevant studies, most assessed Alzheimer's disease (AD) vs healthy controls, used ADNI data, support vector machines and only T1-weighted sequences. Accuracy was highest for differentiating AD from healthy controls, and poor for differentiating healthy controls vs MCI vs AD, or MCI converters vs non-converters. Accuracy increased using combined data types, but not by data source, sample size or machine learning method. DISCUSSION: Machine learning does not differentiate clinically-relevant disease categories yet. More diverse datasets, combinations of different types of data, and close clinical integration of machine learning would help to advance the field.

Lucia Ballerini, Ruggiero Lovreglio, Maria del C. Valdes-Hernandez et al.

Perivascular Spaces (PVS) are a recently recognised feature of Small Vessel Disease (SVD), also indicating neuroinflammation, and are an important part of the brain's circulation and glymphatic drainage system. Quantitative analysis of PVS on Magnetic Resonance Images (MRI) is important for understanding their relationship with neurological diseases. In this work, we propose a segmentation technique based on the 3D Frangi filtering for extraction of PVS from MRI. Based on prior knowledge from neuroradiological ratings of PVS, we used ordered logit models to optimise Frangi filter parameters in response to the variability in the scanner's parameters and study protocols. We optimized and validated our proposed models on two independent cohorts, a dementia sample (N=20) and patients who previously had mild to moderate stroke (N=48). Results demonstrate the robustness and generalisability of our segmentation method. Segmentation-based PVS burden estimates correlated with neuroradiological assessments (Spearman's $ρ$ = 0.74, p $<$ 0.001), suggesting the great potential of our proposed method