arXiv subjects

Neil P. Oxtoby

Publications and source records attributed to Neil P. Oxtoby.

At least 19 recordsLinked to original sources

arXiv2025

CoCoLIT: ControlNet-Conditioned Latent Image Translation for MRI to Amyloid PET Synthesis

Synthesizing amyloid PET scans from the more widely available and accessible structural MRI modality offers a promising, cost-effective approach for large-scale Alzheimer's Disease (AD) screening. This is motivated by evidence that, while MRI does not directly detect amyloid pathology, it may nonetheless encode information correlated with amyloid deposition that can be uncovered through advanced modeling. However, the high dimensionality and structural complexity of 3D neuroimaging data pose significant challenges for existing MRI-to-PET translation methods. Modeling the cross-modality relationship in a lower-dimensional latent space can simplify the learning task and enable more effective translation. As such, we present CoCoLIT (ControlNet-Conditioned Latent Image Translation), a diffusion-based latent generative framework that incorporates three main innovations: (1) a novel Weighted Image Space Loss (WISL) that improves latent representation learning and synthesis quality; (2) a theoretical and empirical analysis of Latent Average Stabilization (LAS), an existing technique used in similar generative models to enhance inference consistency; and (3) the introduction of ControlNet-based conditioning for MRI-to-PET translation. We evaluate CoCoLIT's performance on publicly available datasets and find that our model significantly outperforms state-of-the-art methods on both image-based and amyloid-related metrics. Notably, in amyloid-positivity classification, CoCoLIT outperforms the second-best method with improvements of +10.5% on the internal dataset and +23.7% on the external dataset. The code and models of our approach are available at https://github.com/brAIn-science/CoCoLIT.

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arXiv2023

A coupled-mechanisms modelling framework for neurodegeneration

Computational models of neurodegeneration aim to emulate the evolving pattern of pathology in the brain during neurodegenerative disease, such as Alzheimer's disease. Previous studies have made specific choices on the mechanisms of pathology production and diffusion, or assume that all the subjects lie on the same disease progression trajectory. However, the complexity and heterogeneity of neurodegenerative pathology suggests that multiple mechanisms may contribute synergistically with complex interactions, meanwhile the degree of contribution of each mechanism may vary among individuals. We thus put forward a coupled-mechanisms modelling framework which non-linearly combines the network-topology-informed pathology appearance with the process of pathology spreading within a dynamic modelling system. We account for the heterogeneity of disease by fitting the model at the individual level, allowing the epicenters and rate of progression to vary among subjects. We construct a Bayesian model selection framework to account for feature importance and parameter uncertainty. This provides a combination of mechanisms that best explains the observations for each individual from the ADNI dataset. With the obtained distribution of mechanism importance for each subject, we are able to identify subgroups of patients sharing similar combinations of apparent mechanisms.

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arXiv2023

Expectation Maximization Pseudo Labels

In this paper, we study pseudo-labelling. Pseudo-labelling employs raw inferences on unlabelled data as pseudo-labels for self-training. We elucidate the empirical successes of pseudo-labelling by establishing a link between this technique and the Expectation Maximisation algorithm. Through this, we realise that the original pseudo-labelling serves as an empirical estimation of its more comprehensive underlying formulation. Following this insight, we present a full generalisation of pseudo-labels under Bayes' theorem, termed Bayesian Pseudo Labels. Subsequently, we introduce a variational approach to generate these Bayesian Pseudo Labels, involving the learning of a threshold to automatically select high-quality pseudo labels. In the remainder of the paper, we showcase the applications of pseudo-labelling and its generalised form, Bayesian Pseudo-Labelling, in the semi-supervised segmentation of medical images. Specifically, we focus on: 1) 3D binary segmentation of lung vessels from CT volumes; 2) 2D multi-class segmentation of brain tumours from MRI volumes; 3) 3D binary segmentation of whole brain tumours from MRI volumes; and 4) 3D binary segmentation of prostate from MRI volumes. We further demonstrate that pseudo-labels can enhance the robustness of the learned representations. The code is released in the following GitHub repository: https://github.com/moucheng2017/EMSSL

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arXiv2022

Data-Driven Disease Progression Modelling

Intense debate in the Neurology community before 2010 culminated in hypothetical models of Alzheimer's disease progression: a pathophysiological cascade of biomarkers, each dynamic for only a segment of the full disease timeline. Inspired by this, data-driven disease progression modelling emerged from the computer science community with the aim to reconstruct neurodegenerative disease timelines using data from large cohorts of patients, healthy controls, and prodromal/at-risk individuals. This chapter describes selected highlights from the field, with a focus on utility for understanding and forecasting of disease progression.

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arXiv2022

Bayesian Pseudo Labels: Expectation Maximization for Robust and Efficient Semi-Supervised Segmentation

This paper concerns pseudo labelling in segmentation. Our contribution is fourfold. Firstly, we present a new formulation of pseudo-labelling as an Expectation-Maximization (EM) algorithm for clear statistical interpretation. Secondly, we propose a semi-supervised medical image segmentation method purely based on the original pseudo labelling, namely SegPL. We demonstrate SegPL is a competitive approach against state-of-the-art consistency regularisation based methods on semi-supervised segmentation on a 2D multi-class MRI brain tumour segmentation task and a 3D binary CT lung vessel segmentation task. The simplicity of SegPL allows less computational cost comparing to prior methods. Thirdly, we demonstrate that the effectiveness of SegPL may originate from its robustness against out-of-distribution noises and adversarial attacks. Lastly, under the EM framework, we introduce a probabilistic generalisation of SegPL via variational inference, which learns a dynamic threshold for pseudo labelling during the training. We show that SegPL with variational inference can perform uncertainty estimation on par with the gold-standard method Deep Ensemble.

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arXiv2022

Learning Morphological Feature Perturbations for Calibrated Semi-Supervised Segmentation

We propose MisMatch, a novel consistency-driven semi-supervised segmentation framework which produces predictions that are invariant to learnt feature perturbations. MisMatch consists of an encoder and a two-head decoders. One decoder learns positive attention to the foreground regions of interest (RoI) on unlabelled images thereby generating dilated features. The other decoder learns negative attention to the foreground on the same unlabelled images thereby generating eroded features. We then apply a consistency regularisation on the paired predictions. MisMatch outperforms state-of-the-art semi-supervised methods on a CT-based pulmonary vessel segmentation task and a MRI-based brain tumour segmentation task. In addition, we show that the effectiveness of MisMatch comes from better model calibration than its supervised learning counterpart.

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arXiv2022

Ten years of image analysis and machine learning competitions in dementia

Machine learning methods exploiting multi-parametric biomarkers, especially based on neuroimaging, have huge potential to improve early diagnosis of dementia and to predict which individuals are at-risk of developing dementia. To benchmark algorithms in the field of machine learning and neuroimaging in dementia and assess their potential for use in clinical practice and clinical trials, seven grand challenges have been organized in the last decade. The seven grand challenges addressed questions related to screening, clinical status estimation, prediction and monitoring in (pre-clinical) dementia. There was little overlap in clinical questions, tasks and performance metrics. Whereas this aids providing insight on a broad range of questions, it also limits the validation of results across challenges. The validation process itself was mostly comparable between challenges, using similar methods for ensuring objective comparison, uncertainty estimation and statistical testing. In general, winning algorithms performed rigorous data preprocessing and combined a wide range of input features. Despite high state-of-the-art performances, most of the methods evaluated by the challenges are not clinically used. To increase impact, future challenges could pay more attention to statistical analysis of which factors relate to higher performance, to clinical questions beyond Alzheimer's disease, and to using testing data beyond the Alzheimer's Disease Neuroimaging Initiative. Grand challenges would be an ideal venue for assessing the generalizability of algorithm performance to unseen data of other cohorts. Key for increasing impact in this way are larger testing data sizes, which could be reached by sharing algorithms rather than data to exploit data that cannot be shared.

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arXiv2021

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

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arXiv2021

MisMatch: Calibrated Segmentation via Consistency on Differential Morphological Feature Perturbations with Limited Labels

Semi-supervised learning (SSL) is a promising machine learning paradigm to address the issue of label scarcity in medical imaging. SSL methods were originally developed in image classification. The state-of-the-art SSL methods in image classification utilise consistency regularisation to learn unlabelled predictions which are invariant to input level perturbations. However, image level perturbations violate the cluster assumption in the setting of segmentation. Moreover, existing image level perturbations are hand-crafted which could be sub-optimal. Therefore, it is a not trivial to straightforwardly adapt existing SSL image classification methods in segmentation. In this paper, we propose MisMatch, a semi-supervised segmentation framework based on the consistency between paired predictions which are derived from two differently learnt morphological feature perturbations. MisMatch consists of an encoder and two decoders. One decoder learns positive attention for foreground on unlabelled data thereby generating dilated features of foreground. The other decoder learns negative attention for foreground on the same unlabelled data thereby generating eroded features of foreground. We first develop a 2D U-net based MisMatch framework and perform extensive cross-validation on a CT-based pulmonary vessel segmentation task and show that MisMatch statistically outperforms state-of-the-art semi-supervised methods when only 6.25\% of the total labels are used. In a second experiment, we show that U-net based MisMatch outperforms state-of-the-art methods on an MRI-based brain tumour segmentation task. In a third experiment, we show that a 3D MisMatch outperforms a previous method using input level augmentations, on a left atrium segmentation task. Lastly, we find that the performance improvement of MisMatch over the baseline might originate from its better calibration.

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arXiv2021

Degenerative Adversarial NeuroImage Nets for Brain Scan Simulations: Application in Ageing and Dementia

Accurate and realistic simulation of high-dimensional medical images has become an important research area relevant to many AI-enabled healthcare applications. However, current state-of-the-art approaches lack the ability to produce satisfactory high-resolution and accurate subject-specific images. In this work, we present a deep learning framework, namely 4D-Degenerative Adversarial NeuroImage Net (4D-DANI-Net), to generate high-resolution, longitudinal MRI scans that mimic subject-specific neurodegeneration in ageing and dementia. 4D-DANI-Net is a modular framework based on adversarial training and a set of novel spatiotemporal, biologically-informed constraints. To ensure efficient training and overcome memory limitations affecting such high-dimensional problems, we rely on three key technological advances: i) a new 3D training consistency mechanism called Profile Weight Functions (PWFs), ii) a 3D super-resolution module and iii) a transfer learning strategy to fine-tune the system for a given individual. To evaluate our approach, we trained the framework on 9852 T1-weighted MRI scans from 876 participants in the Alzheimer's Disease Neuroimaging Initiative dataset and held out a separate test set of 1283 MRI scans from 170 participants for quantitative and qualitative assessment of the personalised time series of synthetic images. We performed three evaluations: i) image quality assessment; ii) quantifying the accuracy of regional brain volumes over and above benchmark models; and iii) quantifying visual perception of the synthetic images by medical experts. Overall, both quantitative and qualitative results show that 4D-DANI-Net produces realistic, low-artefact, personalised time series of synthetic T1 MRI that outperforms benchmark models.

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arXiv2020

Learning To Pay Attention To Mistakes

In convolutional neural network based medical image segmentation, the periphery of foreground regions representing malignant tissues may be disproportionately assigned as belonging to the background class of healthy tissues \cite{attenUnet}\cite{AttenUnet2018}\cite{InterSeg}\cite{UnetFrontNeuro}\cite{LearnActiveContour}. This leads to high false negative detection rates. In this paper, we propose a novel attention mechanism to directly address such high false negative rates, called Paying Attention to Mistakes. Our attention mechanism steers the models towards false positive identification, which counters the existing bias towards false negatives. The proposed mechanism has two complementary implementations: (a) "explicit" steering of the model to attend to a larger Effective Receptive Field on the foreground areas; (b) "implicit" steering towards false positives, by attending to a smaller Effective Receptive Field on the background areas. We validated our methods on three tasks: 1) binary dense prediction between vehicles and the background using CityScapes; 2) Enhanced Tumour Core segmentation with multi-modal MRI scans in BRATS2018; 3) segmenting stroke lesions using ultrasound images in ISLES2018. We compared our methods with state-of-the-art attention mechanisms in medical imaging, including self-attention, spatial-attention and spatial-channel mixed attention. Across all of the three different tasks, our models consistently outperform the baseline models in Intersection over Union (IoU) and/or Hausdorff Distance (HD). For instance, in the second task, the "explicit" implementation of our mechanism reduces the HD of the best baseline by more than $26\%$, whilst improving the IoU by more than $3\%$. We believe our proposed attention mechanism can benefit a wide range of medical and computer vision tasks, which suffer from over-detection of background.

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arXiv2020

TADPOLE Challenge: Accurate Alzheimer's disease prediction through crowdsourced forecasting of future data

The TADPOLE Challenge compares the performance of algorithms at predicting the future evolution of individuals at risk of Alzheimer's disease. TADPOLE Challenge participants train their models and algorithms on historical data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Participants are then required to make forecasts of three key outcomes for ADNI-3 rollover participants: clinical diagnosis, ADAS-Cog 13, and total volume of the ventricles -- which are then compared with future measurements. Strong points of the challenge are that the test data did not exist at the time of forecasting (it was acquired afterwards), and that it focuses on the challenging problem of cohort selection for clinical trials by identifying fast progressors. The submission phase of TADPOLE was open until 15 November 2017; since then data has been acquired until April 2019 from 219 subjects with 223 clinical visits and 150 Magnetic Resonance Imaging (MRI) scans, which was used for the evaluation of the participants' predictions. Thirty-three teams participated with a total of 92 submissions. No single submission was best at predicting all three outcomes. For diagnosis prediction, the best forecast (team Frog), which was based on gradient boosting, obtained a multiclass area under the receiver-operating curve (MAUC) of 0.931, while for ventricle prediction the best forecast (team EMC1), which was based on disease progression modelling and spline regression, obtained mean absolute error of 0.41% of total intracranial volume (ICV). For ADAS-Cog 13, no forecast was considerably better than the benchmark mixed effects model (BenchmarkME), provided to participants before the submission deadline. Further analysis can help understand which input features and algorithms are most suitable for Alzheimer's disease prediction and for aiding patient stratification in clinical trials.

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arXiv2019

Degenerative Adversarial NeuroImage Nets: Generating Images that Mimic Disease Progression

Simulating images representative of neurodegenerative diseases is important for predicting patient outcomes and for validation of computational models of disease progression. This capability is valuable for secondary prevention clinical trials where outcomes and screening criteria involve neuroimaging. Traditional computational methods are limited by imposing a parametric model for atrophy and are extremely resource-demanding. Recent advances in deep learning have yielded data-driven models for longitudinal studies (e.g., face ageing) that are capable of generating synthetic images in real-time. Similar solutions can be used to model trajectories of atrophy in the brain, although new challenges need to be addressed to ensure accurate disease progression modelling. Here we propose Degenerative Adversarial NeuroImage Net (DaniNet) --- a new deep learning approach that learns to emulate the effect of neurodegeneration on MRI by simulating atrophy as a function of ages, and disease progression. DaniNet uses an underlying set of Support Vector Regressors (SVRs) trained to capture the patterns of regional intensity changes that accompany disease progression. DaniNet produces whole output images, consisting of 2D-MRI slices that are constrained to match regional predictions from the SVRs. DaniNet is also able to maintain the unique brain morphology of individuals. Adversarial training ensures realistic brain images and smooth temporal progression. We train our model using 9652 T1-weighted (longitudinal) MRI extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We perform quantitative and qualitative evaluations on a separate test set of 1283 images (also from ADNI) demonstrating the ability of DaniNet to produce accurate and convincing synthetic images that emulate disease progression.

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arXiv2019

Disease Knowledge Transfer across Neurodegenerative Diseases

We introduce Disease Knowledge Transfer (DKT), a novel technique for transferring biomarker information between related neurodegenerative diseases. DKT infers robust multimodal biomarker trajectories in rare neurodegenerative diseases even when only limited, unimodal data is available, by transferring information from larger multimodal datasets from common neurodegenerative diseases. DKT is a joint-disease generative model of biomarker progressions, which exploits biomarker relationships that are shared across diseases. Our proposed method allows, for the first time, the estimation of plausible, multimodal biomarker trajectories in Posterior Cortical Atrophy (PCA), a rare neurodegenerative disease where only unimodal MRI data is available. For this we train DKT on a combined dataset containing subjects with two distinct diseases and sizes of data available: 1) a larger, multimodal typical AD (tAD) dataset from the TADPOLE Challenge, and 2) a smaller unimodal Posterior Cortical Atrophy (PCA) dataset from the Dementia Research Centre (DRC), for which only a limited number of Magnetic Resonance Imaging (MRI) scans are available. Although validation is challenging due to lack of data in PCA, we validate DKT on synthetic data and two patient datasets (TADPOLE and PCA cohorts), showing it can estimate the ground truth parameters in the simulation and predict unseen biomarkers on the two patient datasets. While we demonstrated DKT on Alzheimer's variants, we note DKT is generalisable to other forms of related neurodegenerative diseases. Source code for DKT is available online: https://github.com/mrazvan22/dkt.

cs.LG↗

arXiv2019

ABCD Neurocognitive Prediction Challenge 2019: Predicting individual fluid intelligence scores from structural MRI using probabilistic segmentation and kernel ridge regression

We applied several regression and deep learning methods to predict fluid intelligence scores from T1-weighted MRI scans as part of the ABCD Neurocognitive Prediction Challenge (ABCD-NP-Challenge) 2019. We used voxel intensities and probabilistic tissue-type labels derived from these as features to train the models. The best predictive performance (lowest mean-squared error) came from Kernel Ridge Regression (KRR; $λ=10$), which produced a mean-squared error of 69.7204 on the validation set and 92.1298 on the test set. This placed our group in the fifth position on the validation leader board and first place on the final (test) leader board.

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arXiv2019

ABCD Neurocognitive Prediction Challenge 2019: Predicting individual residual fluid intelligence scores from cortical grey matter morphology

We predicted residual fluid intelligence scores from T1-weighted MRI data available as part of the ABCD NP Challenge 2019, using morphological similarity of grey-matter regions across the cortex. Individual structural covariance networks (SCN) were abstracted into graph-theory metrics averaged over nodes across the brain and in data-driven communities/modules. Metrics included degree, path length, clustering coefficient, centrality, rich club coefficient, and small-worldness. These features derived from the training set were used to build various regression models for predicting residual fluid intelligence scores, with performance evaluated both using cross-validation within the training set and using the held-out validation set. Our predictions on the test set were generated with a support vector regression model trained on the training set. We found minimal improvement over predicting a zero residual fluid intelligence score across the sample population, implying that structural covariance networks calculated from T1-weighted MR imaging data provide little information about residual fluid intelligence.

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arXiv2019

DIVE: A spatiotemporal progression model of brain pathology in neurodegenerative disorders

Here we present DIVE: Data-driven Inference of Vertexwise Evolution. DIVE is an image-based disease progression model with single-vertex resolution, designed to reconstruct long-term patterns of brain pathology from short-term longitudinal data sets. DIVE clusters vertex-wise biomarker measurements on the cortical surface that have similar temporal dynamics across a patient population, and concurrently estimates an average trajectory of vertex measurements in each cluster. DIVE uniquely outputs a parcellation of the cortex into areas with common progression patterns, leading to a new signature for individual diseases. DIVE further estimates the disease stage and progression speed for every visit of every subject, potentially enhancing stratification for clinical trials or management. On simulated data, DIVE can recover ground truth clusters and their underlying trajectory, provided the average trajectories are sufficiently different between clusters. We demonstrate DIVE on data from two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Dementia Research Centre (DRC), UK, containing patients with Posterior Cortical Atrophy (PCA) as well as typical Alzheimer's disease (tAD). DIVE finds similar spatial patterns of atrophy for tAD subjects in the two independent datasets (ADNI and DRC), and further reveals distinct patterns of pathology in different diseases (tAD vs PCA) and for distinct types of biomarker data: cortical thickness from Magnetic Resonance Imaging (MRI) vs amyloid load from Positron Emission Tomography (PET). Finally, DIVE can be used to estimate a fine-grained spatial distribution of pathology in the brain using any kind of voxelwise or vertexwise measures including Jacobian compression maps, fractional anisotropy (FA) maps from diffusion imaging or other PET measures. DIVE source code is available online: https://github.com/mrazvan22/dive

cs.CV↗

arXiv2018

TADPOLE Challenge: Prediction of Longitudinal Evolution in Alzheimer's Disease

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge compares the performance of algorithms at predicting future evolution of individuals at risk of Alzheimer's disease. TADPOLE Challenge participants train their models and algorithms on historical data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study or any other datasets to which they have access. Participants are then required to make monthly forecasts over a period of 5 years from January 2018, of three key outcomes for ADNI-3 rollover participants: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. These individual forecasts are later compared with the corresponding future measurements in ADNI-3 (obtained after the TADPOLE submission deadline). The first submission phase of TADPOLE was open for prize-eligible submissions between 15 June and 15 November 2017. The submission system remains open via the website: https://tadpole.grand-challenge.org, although since 15 November 2017 submissions are not eligible for the first round of prizes. This paper describes the design of the TADPOLE Challenge.

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