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Vision transformers are effective deep learning models for vision tasks, including medical image segmentation. However, they lack efficiency and translational invariance, unlike convolutional neural networks (CNNs). To model long-range interactions in 3D brain lesion segmentation, we propose an all-convolutional transformer block variant of the U-Net architecture. We demonstrate that our model provides the greatest compromise in three factors: performance competitive with the state-of-the-art; parameter efficiency of a CNN; and the favourable inductive biases of a transformer. Our public implementation is available at https://github.com/liamchalcroft/MDUNet .

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Data used in image segmentation are not always defined on the same grid. This is particularly true for medical images, where the resolution, field-of-view and orientation can differ across channels and subjects. Images and labels are therefore commonly resampled onto the same grid, as a pre-processing step. However, the resampling operation introduces partial volume effects and blurring, thereby changing the effective resolution and reducing the contrast between structures. In this paper we propose a splat layer, which automatically handles resolution mismatches in the input data. This layer pushes each image onto a mean space where the forward pass is performed. As the splat operator is the adjoint to the resampling operator, the mean-space prediction can be pulled back to the native label space, where the loss function is computed. Thus, the need for explicit resolution adjustment using interpolation is removed. We show on two publicly available datasets, with simulated and real multi-modal magnetic resonance images, that this model improves segmentation results compared to resampling as a pre-processing step., Comment: Accepted for MIUA 2022

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

Segmentation of brain magnetic resonance images (MRI) into anatomical regions is a useful task in neuroimaging. Manual annotation is time consuming and expensive, so having a fully automated and general purpose brain segmentation algorithm is highly desirable. To this end, we propose a patched-based label propagation approach based on a generative model with latent variables. Once trained, our Factorisation-based Image Labelling (FIL) model is able to label target images with a variety of image contrasts. We compare the effectiveness of our proposed model against the state-of-the-art using data from the MICCAI 2012 Grand Challenge and Workshop on Multi-Atlas Labeling. As our approach is intended to be general purpose, we also assess how well it can handle domain shift by labelling images of the same subjects acquired with different MR contrasts.

Purpose: Inter-scan motion is a substantial source of error in $R_1$ estimation, and can be expected to increase at 7T where $B_1$ fields are more inhomogeneous. The established correction scheme does not translate to 7T since it requires a body coil reference. Here we introduce two alternatives that outperform the established method. Since they compute relative sensitivities they do not require body coil images. Theory: The proposed methods use coil-combined magnitude images to obtain the relative coil sensitivities. The first method efficiently computes the relative sensitivities via a simple ratio; the second by fitting a more sophisticated generative model. Methods: $R_1$ maps were computed using the variable flip angle (VFA) approach. Multiple datasets were acquired at 3T and 7T, with and without motion between the acquisition of the VFA volumes. $R_1$ maps were constructed without correction, with the proposed corrections, and (at 3T) with the previously established correction scheme. Results: At 3T, the proposed methods outperform the baseline method. Inter-scan motion artefacts were also reduced at 7T. However, reproducibility only converged on that of the no motion condition if position-specific transmit field effects were also incorporated. Conclusion: The proposed methods simplify inter-scan motion correction of $R_1$ maps and are applicable at both 3T and 7T, where a body coil is typically not available. The open-source code for all methods is made publicly available.

While convolutional neural networks (CNNs) trained by back-propagation have seen unprecedented success at semantic segmentation tasks, they are known to struggle on out-of-distribution data. Markov random fields (MRFs) on the other hand, encode simpler distributions over labels that, although less flexible than UNets, are less prone to over-fitting. In this paper, we propose to fuse both strategies by computing the product of distributions of a UNet and an MRF. As this product is intractable, we solve for an approximate distribution using an iterative mean-field approach. The resulting MRF-UNet is trained jointly by back-propagation. Compared to other works using conditional random fields (CRFs), the MRF has no dependency on the imaging data, which should allow for less over-fitting. We show on 3D neuroimaging data that this novel network improves generalisation to out-of-distribution samples. Furthermore, it allows the overall number of parameters to be reduced while preserving high accuracy. These results suggest that a classic MRF smoothness prior can allow for less over-fitting when principally integrated into a CNN model. Our implementation is available at https://github.com/balbasty/nitorch., Comment: Accepted at MIDL 2021

Quantitative MR imaging is increasingly favoured for its richer information content and standardised measures. However, computing quantitative parameter maps, such as those encoding longitudinal relaxation rate (R1), apparent transverse relaxation rate (R2*) or magnetisation-transfer saturation (MTsat), involves inverting a highly non-linear function. Many methods for deriving parameter maps assume perfect measurements and do not consider how noise is propagated through the estimation procedure, resulting in needlessly noisy maps. Instead, we propose a probabilistic generative (forward) model of the entire dataset, which is formulated and inverted to jointly recover (log) parameter maps with a well-defined probabilistic interpretation (e.g., maximum likelihood or maximum a posteriori). The second order optimisation we propose for model fitting achieves rapid and stable convergence thanks to a novel approximate Hessian. We demonstrate the utility of our flexible framework in the context of recovering more accurate maps from data acquired using the popular multi-parameter mapping protocol. We also show how to incorporate a joint total variation prior to further decrease the noise in the maps, noting that the probabilistic formulation allows the uncertainty on the recovered parameter maps to be estimated. Our implementation uses a PyTorch backend and benefits from GPU acceleration. It is available at https://github.com/balbasty/nitorch., Comment: 20 pages, 6 figures, accepted at Medical Image Analysis

We describe a diffeomorphic registration algorithm that allows groups of images to be accurately aligned to a common space, which we intend to incorporate into the SPM software. The idea is to perform inference in a probabilistic graphical model that accounts for variability in both shape and appearance. The resulting framework is general and entirely unsupervised. The model is evaluated at inter-subject registration of 3D human brain scans. Here, the main modeling assumption is that individual anatomies can be generated by deforming a latent 'average' brain. The method is agnostic to imaging modality and can be applied with no prior processing. We evaluate the algorithm using freely available, manually labelled datasets. In this validation we achieve state-of-the-art results, within reasonable runtimes, against previous state-of-the-art widely used, inter-subject registration algorithms. On the unprocessed dataset, the increase in overlap score is over 17%. These results demonstrate the benefits of using informative computational anatomy frameworks for nonlinear registration., Comment: Accepted for MICCAI 2020

Quantitative magnetic resonance imaging (qMRI) derives tissue-specific parameters -- such as the apparent transverse relaxation rate R2*, the longitudinal relaxation rate R1 and the magnetisation transfer saturation -- that can be compared across sites and scanners and carry important information about the underlying microstructure. The multi-parameter mapping (MPM) protocol takes advantage of multi-echo acquisitions with variable flip angles to extract these parameters in a clinically acceptable scan time. In this context, ESTATICS performs a joint loglinear fit of multiple echo series to extract R2* and multiple extrapolated intercepts, thereby improving robustness to motion and decreasing the variance of the estimators. In this paper, we extend this model in two ways: (1) by introducing a joint total variation (JTV) prior on the intercepts and decay, and (2) by deriving a nonlinear maximum \emph{a posteriori} estimate. We evaluated the proposed algorithm by predicting left-out echoes in a rich single-subject dataset. In this validation, we outperformed other state-of-the-art methods and additionally showed that the proposed approach greatly reduces the variance of the estimated maps, without introducing bias., Comment: 11 pages, 2 figures, 1 table, conference paper, accepted at MICCAI 2020

In medical imaging it is common practice to acquire a wide range of modalities (MRI, CT, PET, etc.), to highlight different structures or pathologies. As patient movement between scans or scanning session is unavoidable, registration is often an essential step before any subsequent image analysis. In this paper, we introduce a cost function based on joint total variation for such multimodal image registration. This cost function has the advantage of enabling principled, groupwise alignment of multiple images, whilst being insensitive to strong intensity non-uniformities. We evaluate our algorithm on rigidly aligning both simulated and real 3D brain scans. This validation shows robustness to strong intensity non-uniformities and low registration errors for CT/PET to MRI alignment. Our implementation is publicly available at https://github.com/brudfors/coregistration-njtv.

We present a tool for resolution recovery in multimodal clinical magnetic resonance imaging (MRI). Such images exhibit great variability, both biological and instrumental. This variability makes automated processing with neuroimaging analysis software very challenging. This leaves intelligence extractable only from large-scale analyses of clinical data untapped, and impedes the introduction of automated predictive systems in clinical care. The tool presented in this paper enables such processing, via inference in a generative model of thick-sliced, multi-contrast MR scans. All model parameters are estimated from the observed data, without the need for manual tuning. The model-driven nature of the approach means that no type of training is needed for applicability to the diversity of MR contrasts present in a clinical context. We show on simulated data that the proposed approach outperforms conventional model-based techniques, and on a large hospital dataset of multimodal MRIs that the tool can successfully super-resolve very thick-sliced images. The implementation is available from https://github.com/brudfors/spm_superres.

Automatically generating one medical imaging modality from another is known as medical image translation, and has numerous interesting applications. This paper presents an interpretable generative modelling approach to medical image translation. By allowing a common model for group-wise normalisation and segmentation of brain scans to handle missing data, the model allows for predicting entirely missing modalities from one, or a few, MR contrasts. Furthermore, the model can be trained on a fairly small number of subjects. The proposed model is validated on three clinically relevant scenarios. Results appear promising and show that a principled, probabilistic model of the relationship between multi-channel signal intensities can be used to infer missing modalities -- both MR contrasts and CT images., Comment: Accepted to the Simulation and Synthesis in Medical Imaging (SASHIMI) workshop at MICCAI 2019

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; $\lambda=10$), 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., Comment: Winning entry in the ABCD Neurocognitive Prediction Challenge at MICCAI 2019. 7 pages plus references, 3 figures, 1 table

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., Comment: 8 pages plus references, 3 figures, 2 tables. Submission to the ABCD Neurocognitive Prediction Challenge at MICCAI 2019

Although convolutional neural networks (CNNs) currently dominate competitions on image segmentation, for neuroimaging analysis tasks, more classical generative approaches based on mixture models are still used in practice to parcellate brains. To bridge the gap between the two, in this paper we propose a marriage between a probabilistic generative model, which has been shown to be robust to variability among magnetic resonance (MR) images acquired via different imaging protocols, and a CNN. The link is in the prior distribution over the unknown tissue classes, which are classically modelled using a Markov random field. In this work we model the interactions among neighbouring pixels by a type of recurrent CNN, which can encode more complex spatial interactions. We validate our proposed model on publicly available MR data, from different centres, and show that it generalises across imaging protocols. This result demonstrates a successful and principled inclusion of a CNN in a generative model, which in turn could be adapted by any probabilistic generative approach for image segmentation., Comment: Accepted for the international conference on Information Processing in Medical Imaging (IPMI) 2019, camera ready version

This paper presents a generative model for super-resolution in routine clinical magnetic resonance images (MRI), of arbitrary orientation and contrast. The model recasts the recovery of high resolution images as an inverse problem, in which a forward model simulates the slice-select profile of the MR scanner. The paper introduces a prior based on multi-channel total variation for MRI super-resolution. Bias-variance trade-off is handled by estimating hyper-parameters from the low resolution input scans. The model was validated on a large database of brain images. The validation showed that the model can improve brain segmentation, that it can recover anatomical information between images of different MR contrasts, and that it generalises well to the large variability present in MR images of different subjects. The implementation is freely available at https://github.com/brudfors/spm_superres

This paper presents a framework for automatically learning shape and appearance models for medical (and certain other) images. It is based on the idea that having a more accurate shape and appearance model leads to more accurate image registration, which in turn leads to a more accurate shape and appearance model. This leads naturally to an iterative scheme, which is based on a probabilistic generative model that is fit using Gauss-Newton updates within an EM-like framework. It was developed with the aim of enabling distributed privacy-preserving analysis of brain image data, such that shared information (shape and appearance basis functions) may be passed across sites, whereas latent variables that encode individual images remain secure within each site. These latent variables are proposed as features for privacy-preserving data mining applications. The approach is demonstrated qualitatively on the KDEF dataset of 2D face images, showing that it can align images that traditionally require shape and appearance models trained using manually annotated data (manually defined landmarks etc.). It is applied to MNIST dataset of handwritten digits to show its potential for machine learning applications, particularly when training data is limited. The model is able to handle ``missing data'', which allows it to be cross-validated according to how well it can predict left-out voxels. The suitability of the derived features for classifying individuals into patient groups was assessed by applying it to a dataset of over 1,900 segmented T1-weighted MR images, which included images from the COBRE and ABIDE datasets., Comment: 61 pages, 16 figures (some downsampled by a factor of 4), submitted to MedIA

Shape modelling describes methods aimed at capturing the natural variability of shapes and commonly relies on probabilistic interpretations of dimensionality reduction techniques such as principal component analysis. Due to their computational complexity when dealing with dense deformation models such as diffeomorphisms, previous attempts have focused on explicitly reducing their dimension, diminishing de facto their flexibility and ability to model complex shapes such as brains. In this paper, we present a generative model of shape that allows the covariance structure of deformations to be captured without squashing their domain, resulting in better normalisation. An efficient inference scheme based on Gauss-Newton optimisation is used, which enables processing of 3D neuroimaging data. We trained this algorithm on segmented brains from the OASIS database, generating physiologically meaningful deformation trajectories. To prove the model's robustness, we applied it to unseen data, which resulted in equivalent fitting scores., Comment: 8 pages, 4 figures, conference paper, accepted at MICCAI 2018