On the Initialization of Long Short-Term Memory Networks

Weight initialization is important for faster convergence and stability of deep neural networks training. In this paper, a robust initialization method is developed to address the training instability in long short-term memory (LSTM) networks. It is based on a normalized random initialization of the network weights that aims at preserving the variance of the network input and output in the same range. The method is applied to standard LSTMs for univariate time series regression and to LSTMs robust to missing values for multivariate disease progression modeling. The results show that in all cases, the proposed initialization method outperforms the state-of-the-art initialization techniques in terms of training convergence and generalization performance of the obtained solution.

Privacy-preserving Federated Brain Tumour Segmentation

Due to medical data privacy regulations, it is often infeasible to collect and share patient data in a centralised data lake. This poses challenges for training machine learning algorithms, such as deep convolutional networks, which often require large numbers of diverse training examples. Federated learning sidesteps this difficulty by bringing code to the patient data owners and only sharing intermediate model training updates among them. Although a high-accuracy model could be achieved by appropriately aggregating these model updates, the model shared could indirectly leak the local training examples. In this paper, we investigate the feasibility of applying differential-privacy techniques to protect the patient data in a federated learning setup. We implement and evaluate practical federated learning systems for brain tumour segmentation on the BraTS dataset. The experimental results show that there is a trade-off between model performance and privacy protection costs.

Multi-Domain Adaptation in Brain MRI through Paired Consistency and Adversarial Learning

Supervised learning algorithms trained on medical images will often fail to generalize across changes in acquisition parameters. Recent work in domain adaptation addresses this challenge and successfully leverages labeled data in a source domain to perform well on an unlabeled target domain. Inspired by recent work in semi-supervised learning we introduce a novel method to adapt from one source domain to $n$ target domains (as long as there is paired data covering all domains). Our multi-domain adaptation method utilises a consistency loss combined with adversarial learning. We provide results on white matter lesion hyperintensity segmentation from brain MRIs using the MICCAI 2017 challenge data as the source domain and two target domains. The proposed method significantly outperforms other domain adaptation baselines.

Let's agree to disagree: learning highly debatable multirater labelling

Classification and differentiation of small pathological objects may greatly vary among human raters due to differences in training, expertise and their consistency over time. In a radiological setting, objects commonly have high within-class appearance variability whilst sharing certain characteristics across different classes, making their distinction even more difficult. As an example, markers of cerebral small vessel disease, such as enlarged perivascular spaces (EPVS) and lacunes, can be very varied in their appearance while exhibiting high inter-class similarity, making this task highly challenging for human raters. In this work, we investigate joint models of individual rater behaviour and multirater consensus in a deep learning setting, and apply it to a brain lesion object-detection task. Results show that jointly modelling both individual and consensus estimates leads to significant improvements in performance when compared to directly predicting consensus labels, while also allowing the characterization of human-rater consistency.

Stochastic Filter Groups for Multi-Task CNNs: Learning Specialist and Generalist Convolution Kernels

The performance of multi-task learning in Convolutional Neural Networks (CNNs) hinges on the design of feature sharing between tasks within the architecture. The number of possible sharing patterns are combinatorial in the depth of the network and the number of tasks, and thus hand-crafting an architecture, purely based on the human intuitions of task relationships can be time-consuming and suboptimal. In this paper, we present a probabilistic approach to learning task-specific and shared representations in CNNs for multi-task learning. Specifically, we propose "stochastic filter groups'' (SFG), a mechanism to assign convolution kernels in each layer to "specialist'' or "generalist'' groups, which are specific to or shared across different tasks, respectively. The SFG modules determine the connectivity between layers and the structures of task-specific and shared representations in the network. We employ variational inference to learn the posterior distribution over the possible grouping of kernels and network parameters. Experiments demonstrate that the proposed method generalises across multiple tasks and shows improved performance over baseline methods.

Robust parametric modeling of Alzheimer's disease progression

Quantitative characterization of disease progression using longitudinal data can provide long-term predictions for the pathological stages of individuals. This work studies robust modeling of Alzheimer's disease progression using parametric methods. The proposed method linearly maps individual's chronological age to a disease progression score (DPS) and robustly fits a constrained generalized logistic function to the longitudinal dynamic of a biomarker as a function of the DPS using M-estimation. Robustness of the estimates is quantified using bootstrapping via Monte Carlo resampling, and the inflection points are used to temporally order the modeled biomarkers in the disease course. Moreover, kernel density estimation is applied to the obtained DPSs for clinical status prediction using a Bayesian classifier. Different M-estimators and logistic functions, including a new generalized type proposed in this study called modified Stannard, are evaluated on the ADNI database for robust modeling of volumetric MRI and PET biomarkers, as well as neuropsychological tests. The results show that the modified Stannard function fitted using the modified Huber loss achieves the best modeling performance with a mean of median absolute errors (MMAE) of 0.059 across all biomarkers and bootstraps. In addition, applied to the ADNI test set, this model achieves a multi-class area under the ROC curve (MAUC) of 0.87 in clinical status prediction, and it significantly outperforms an analogous state-of-the-art method with a biomarker modeling MMAE of 0.059 vs. 0.061 (p < 0.001). Finally, the experiments show that the proposed model, trained using abundant ADNI data, generalizes well to data from the independent NACC database, where both modeling and diagnostic performance are significantly improved (p < 0.001) compared with using a model trained using relatively sparse NACC data.

As easy as 1, 2... 4? Uncertainty in counting tasks for medical imaging

Counting is a fundamental task in biomedical imaging and count is an important biomarker in a number of conditions. Estimating the uncertainty in the measurement is thus vital to making definite, informed conclusions. In this paper, we first compare a range of existing methods to perform counting in medical imaging and suggest ways of deriving predictive intervals from these. We then propose and test a method for calculating intervals as an output of a multi-task network. These predictive intervals are optimised to be as narrow as possible, while also enclosing a desired percentage of the data. We demonstrate the effectiveness of this technique on histopathological cell counting and white matter hyperintensity counting. Finally, we offer insight into other areas where this technique may apply.

Standardized Assessment of Automatic Segmentation of White Matter Hyperintensities and Results of the WMH Segmentation Challenge

Quantification of cerebral white matter hyperintensities (WMH) of presumed vascular origin is of key importance in many neurological research studies. Currently, measurements are often still obtained from manual segmentations on brain MR images, which is a laborious procedure. Automatic WMH segmentation methods exist, but a standardized comparison of the performance of such methods is lacking. We organized a scientific challenge, in which developers could evaluate their method on a standardized multi-center/-scanner image dataset, giving an objective comparison: the WMH Segmentation Challenge (https://wmh.isi.uu.nl/). Sixty T1+FLAIR images from three MR scanners were released with manual WMH segmentations for training. A test set of 110 images from five MR scanners was used for evaluation. Segmentation methods had to be containerized and submitted to the challenge organizers. Five evaluation metrics were used to rank the methods: (1) Dice similarity coefficient, (2) modified Hausdorff distance (95th percentile), (3) absolute log-transformed volume difference, (4) sensitivity for detecting individual lesions, and (5) F1-score for individual lesions. Additionally, methods were ranked on their inter-scanner robustness. Twenty participants submitted their method for evaluation. This paper provides a detailed analysis of the results. In brief, there is a cluster of four methods that rank significantly better than the other methods, with one clear winner. The inter-scanner robustness ranking shows that not all methods generalize to unseen scanners. The challenge remains open for future submissions and provides a public platform for method evaluation.

Training recurrent neural networks robust to incomplete data: application to Alzheimer's disease progression modeling

Disease progression modeling (DPM) using longitudinal data is a challenging machine learning task. Existing DPM algorithms neglect temporal dependencies among measurements, make parametric assumptions about biomarker trajectories, do not model multiple biomarkers jointly, and need an alignment of subjects' trajectories. In this paper, recurrent neural networks (RNNs) are utilized to address these issues. However, in many cases, longitudinal cohorts contain incomplete data, which hinders the application of standard RNNs and requires a pre-processing step such as imputation of the missing values. Instead, we propose a generalized training rule for the most widely used RNN architecture, long short-term memory (LSTM) networks, that can handle both missing predictor and target values. The proposed LSTM algorithm is applied to model the progression of Alzheimer's disease (AD) using six volumetric magnetic resonance imaging (MRI) biomarkers, i.e., volumes of ventricles, hippocampus, whole brain, fusiform, middle temporal gyrus, and entorhinal cortex, and it is compared to standard LSTM networks with data imputation and a parametric, regression-based DPM method. The results show that the proposed algorithm achieves a significantly lower mean absolute error (MAE) than the alternatives with p < 0.05 using Wilcoxon signed rank test in predicting values of almost all of the MRI biomarkers. Moreover, a linear discriminant analysis (LDA) classifier applied to the predicted biomarker values produces a significantly larger AUC of 0.90 vs. at most 0.84 with p < 0.001 using McNemar's test for clinical diagnosis of AD. Inspection of MAE curves as a function of the amount of missing data reveals that the proposed LSTM algorithm achieves the best performance up until more than 74% missing values. Finally, it is illustrated how the method can successfully be applied to data with varying time intervals.

A large annotated medical image dataset for the development and evaluation of segmentation algorithms

Semantic segmentation of medical images aims to associate a pixel with a label in a medical image without human initialization. The success of semantic segmentation algorithms is contingent on the availability of high-quality imaging data with corresponding labels provided by experts. We sought to create a large collection of annotated medical image datasets of various clinically relevant anatomies available under open source license to facilitate the development of semantic segmentation algorithms. Such a resource would allow: 1) objective assessment of general-purpose segmentation methods through comprehensive benchmarking and 2) open and free access to medical image data for any researcher interested in the problem domain. Through a multi-institutional effort, we generated a large, curated dataset representative of several highly variable segmentation tasks that was used in a crowd-sourced challenge - the Medical Segmentation Decathlon held during the 2018 Medical Image Computing and Computer Aided Interventions Conference in Granada, Spain. Here, we describe these ten labeled image datasets so that these data may be effectively reused by the research community.