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Daniel C. Alexander

Publications and source records attributed to Daniel C. Alexander.

At least 73 records · Page 4Linked to original sources

Domain-agnostic segmentation of thalamic nuclei from joint structural and diffusion MRI

The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI.

eess.IV↗

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.

cs.CV↗

Low-field magnetic resonance image enhancement via stochastic image quality transfer

Low-field (<1T) magnetic resonance imaging (MRI) scanners remain in widespread use in low- and middle-income countries (LMICs) and are commonly used for some applications in higher income countries e.g. for small child patients with obesity, claustrophobia, implants, or tattoos. However, low-field MR images commonly have lower resolution and poorer contrast than images from high field (1.5T, 3T, and above). Here, we present Image Quality Transfer (IQT) to enhance low-field structural MRI by estimating from a low-field image the image we would have obtained from the same subject at high field. Our approach uses (i) a stochastic low-field image simulator as the forward model to capture uncertainty and variation in the contrast of low-field images corresponding to a particular high-field image, and (ii) an anisotropic U-Net variant specifically designed for the IQT inverse problem. We evaluate the proposed algorithm both in simulation and using multi-contrast (T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR)) clinical low-field MRI data from an LMIC hospital. We show the efficacy of IQT in improving contrast and resolution of low-field MR images. We demonstrate that IQT-enhanced images have potential for enhancing visualisation of anatomical structures and pathological lesions of clinical relevance from the perspective of radiologists. IQT is proved to have capability of boosting the diagnostic value of low-field MRI, especially in low-resource settings.

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A hybrid CNN-RNN approach for survival analysis in a Lung Cancer Screening study

In this study, we present a hybrid CNN-RNN approach to investigate long-term survival of subjects in a lung cancer screening study. Subjects who died of cardiovascular and respiratory causes were identified whereby the CNN model was used to capture imaging features in the CT scans and the RNN model was used to investigate time series and thus global information. The models were trained on subjects who underwent cardiovascular and respiratory deaths and a control cohort matched to participant age, gender, and smoking history. The combined model can achieve an AUC of 0.76 which outperforms humans at cardiovascular mortality prediction. The corresponding F1 and Matthews Correlation Coefficient are 0.63 and 0.42 respectively. The generalisability of the model is further validated on an 'external' cohort. The same models were applied to survival analysis with the Cox Proportional Hazard model. It was demonstrated that incorporating the follow-up history can lead to improvement in survival prediction. The Cox neural network can achieve an IPCW C-index of 0.75 on the internal dataset and 0.69 on an external dataset. Delineating imaging features associated with long-term survival can help focus preventative interventions appropriately, particularly for under-recognised pathologies thereby potentially reducing patient morbidity.

cs.LG↗

Deformably-Scaled Transposed Convolution

Transposed convolution is crucial for generating high-resolution outputs, yet has received little attention compared to convolution layers. In this work we revisit transposed convolution and introduce a novel layer that allows us to place information in the image selectively and choose the `stroke breadth' at which the image is synthesized, whilst incurring a small additional parameter cost. For this we introduce three ideas: firstly, we regress offsets to the positions where the transpose convolution results are placed; secondly we broadcast the offset weight locations over a learnable neighborhood; and thirdly we use a compact parametrization to share weights and restrict offsets. We show that simply substituting upsampling operators with our novel layer produces substantial improvements across tasks as diverse as instance segmentation, object detection, semantic segmentation, generative image modeling, and 3D magnetic resonance image enhancement, while outperforming all existing variants of transposed convolutions. Our novel layer can be used as a drop-in replacement for 2D and 3D upsampling operators and the code will be publicly available.

cs.CV↗

Progressive Subsampling for Oversampled Data - Application to Quantitative MRI

We present PROSUB: PROgressive SUBsampling, a deep learning based, automated methodology that subsamples an oversampled data set (e.g. multi-channeled 3D images) with minimal loss of information. We build upon a recent dual-network approach that won the MICCAI MUlti-DIffusion (MUDI) quantitative MRI measurement sampling-reconstruction challenge, but suffers from deep learning training instability, by subsampling with a hard decision boundary. PROSUB uses the paradigm of recursive feature elimination (RFE) and progressively subsamples measurements during deep learning training, improving optimization stability. PROSUB also integrates a neural architecture search (NAS) paradigm, allowing the network architecture hyperparameters to respond to the subsampling process. We show PROSUB outperforms the winner of the MUDI MICCAI challenge, producing large improvements >18% MSE on the MUDI challenge sub-tasks and qualitative improvements on downstream processes useful for clinical applications. We also show the benefits of incorporating NAS and analyze the effect of PROSUB's components. As our method generalizes to other problems beyond MRI measurement selection-reconstruction, our code is https://github.com/sbb-gh/PROSUB

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Fitting a Directional Microstructure Model to Diffusion-Relaxation MRI Data with Self-Supervised Machine Learning

Machine learning is a powerful approach for fitting microstructural models to diffusion MRI data. Early machine learning microstructure imaging implementations trained regressors to estimate model parameters in a supervised way, using synthetic training data with known ground truth. However, a drawback of this approach is that the choice of training data impacts fitted parameter values. Self-supervised learning is emerging as an attractive alternative to supervised learning in this context. Thus far, both supervised and self-supervised learning have typically been applied to isotropic models, such as intravoxel incoherent motion (IVIM), as opposed to models where the directionality of anisotropic structures is also estimated. In this paper, we demonstrate self-supervised machine learning model fitting for a directional microstructural model. In particular, we fit a combined T1-ball-stick model to the multidimensional diffusion (MUDI) challenge diffusion-relaxation dataset. Our self-supervised approach shows clear improvements in parameter estimation and computational time, for both simulated and in-vivo brain data, compared to standard non-linear least squares fitting. Code for the artificial neural net constructed for this study is available for public use from the following GitHub repository: https://github.com/jplte/deep-T1-ball-stick

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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.

cs.CV↗

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.

cs.CV↗

Survival Analysis for Idiopathic Pulmonary Fibrosis using CT Images and Incomplete Clinical Data

Idiopathic Pulmonary Fibrosis (IPF) is an inexorably progressive fibrotic lung disease with a variable and unpredictable rate of progression. CT scans of the lungs inform clinical assessment of IPF patients and contain pertinent information related to disease progression. In this work, we propose a multi-modal method that uses neural networks and memory banks to predict the survival of IPF patients using clinical and imaging data. The majority of clinical IPF patient records have missing data (e.g. missing lung function tests). To this end, we propose a probabilistic model that captures the dependencies between the observed clinical variables and imputes missing ones. This principled approach to missing data imputation can be naturally combined with a deep survival analysis model. We show that the proposed framework yields significantly better survival analysis results than baselines in terms of concordance index and integrated Brier score. Our work also provides insights into novel image-based biomarkers that are linked to mortality.

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Learning to Downsample for Segmentation of Ultra-High Resolution Images

Many computer vision systems require low-cost segmentation algorithms based on deep learning, either because of the enormous size of input images or limited computational budget. Common solutions uniformly downsample the input images to meet memory constraints, assuming all pixels are equally informative. In this work, we demonstrate that this assumption can harm the segmentation performance because the segmentation difficulty varies spatially. We combat this problem by introducing a learnable downsampling module, which can be optimised together with the given segmentation model in an end-to-end fashion. We formulate the problem of training such downsampling module as optimisation of sampling density distributions over the input images given their low-resolution views. To defend against degenerate solutions (e.g. over-sampling trivial regions like the backgrounds), we propose a regularisation term that encourages the sampling locations to concentrate around the object boundaries. We find the downsampling module learns to sample more densely at difficult locations, thereby improving the segmentation performance. Our experiments on benchmarks of high-resolution street view, aerial and medical images demonstrate substantial improvements in terms of efficiency-and-accuracy trade-off compared to both uniform downsampling and two recent advanced downsampling techniques.

cs.CV↗

VAFO-Loss: VAscular Feature Optimised Loss Function for Retinal Artery/Vein Segmentation

Estimating clinically-relevant vascular features following vessel segmentation is a standard pipeline for retinal vessel analysis, which provides potential ocular biomarkers for both ophthalmic disease and systemic disease. In this work, we integrate these clinical features into a novel vascular feature optimised loss function (VAFO-Loss), in order to regularise networks to produce segmentation maps, with which more accurate vascular features can be derived. Two common vascular features, vessel density and fractal dimension, are identified to be sensitive to intra-segment misclassification, which is a well-recognised problem in multi-class artery/vein segmentation particularly hindering the estimation of these vascular features. Thus we encode these two features into VAFO-Loss. We first show that incorporating our end-to-end VAFO-Loss in standard segmentation networks indeed improves vascular feature estimation, yielding quantitative improvement in stroke incidence prediction, a clinical downstream task. We also report a technically interesting finding that the trained segmentation network, albeit biased by the feature optimised loss VAFO-Loss, shows statistically significant improvement in segmentation metrics, compared to those trained with other state-of-the-art segmentation losses.

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Impact of within-voxel heterogeneity in fibre geometry on spherical deconvolution

Axons in white matter have been shown to have varying geometries within a bundle using ex vivo imaging techniques, but what does this mean for diffusion MRI (dMRI) based spherical deconvolution (SD)? SD attempts to estimate the fibre orientation distribution function (fODF) by assuming a single dMRI fibre response function (FRF) for all white matter populations and deconvolving this FRF from the dMRI signal at each voxel to estimate the fODF. Variable fibre geometry within a bundle however suggests the FRF might not be constant even within a single voxel. We test what impact realistic fibre geometry has on SD by simulating the dMRI signal in a range of realistic white matter numerical phantoms, including synthetic phantoms and real axons segmented from electron microscopy. We demonstrate that variable fibre geometry leads to a variable FRF across axons and that in general no single FRF is effective to recover the underlying fibre orientation distribution function (fODF). This finding suggests that assuming a single FRF can lead to misestimation of the fODF, causing further downstream errors in techniques such as tractography.

physics.med-ph↗

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.

cs.LG↗

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.

q-bio.PE↗

Learning to Address Intra-segment Misclassification in Retinal Imaging

Accurate multi-class segmentation is a long-standing challenge in medical imaging, especially in scenarios where classes share strong similarity. Segmenting retinal blood vessels in retinal photographs is one such scenario, in which arteries and veins need to be identified and differentiated from each other and from the background. Intra-segment misclassification, i.e. veins classified as arteries or vice versa, frequently occurs when arteries and veins intersect, whereas in binary retinal vessel segmentation, error rates are much lower. We thus propose a new approach that decomposes multi-class segmentation into multiple binary, followed by a binary-to-multi-class fusion network. The network merges representations of artery, vein, and multi-class feature maps, each of which are supervised by expert vessel annotation in adversarial training. A skip-connection based merging process explicitly maintains class-specific gradients to avoid gradient vanishing in deep layers, to favor the discriminative features. The results show that, our model respectively improves F1-score by 4.4\%, 5.1\%, and 4.2\% compared with three state-of-the-art deep learning based methods on DRIVE-AV, LES-AV, and HRF-AV data sets. Code: https://github.com/rmaphoh/Learning-AVSegmentation

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Evaluation of automated airway morphological quantification for assessing fibrosing lung disease

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that systematically parcellates the airway tree into its lobes and generational branches from a deep learning based airway segmentation, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent.

physics.med-ph↗

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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