Simultaneous synthesis of FLAIR and segmentation of white matter hypointensities from T1 MRIs

Segmenting vascular pathologies such as white matter lesions in Brain magnetic resonance images (MRIs) require acquisition of multiple sequences such as T1-weighted (T1-w) --on which lesions appear hypointense-- and fluid attenuated inversion recovery (FLAIR) sequence --where lesions appear hyperintense--. However, most of the existing retrospective datasets do not consist of FLAIR sequences. Existing missing modality imputation methods separate the process of imputation, and the process of segmentation. In this paper, we propose a method to link both modality imputation and segmentation using convolutional neural networks. We show that by jointly optimizing the imputation network and the segmentation network, the method not only produces more realistic synthetic FLAIR images from T1-w images, but also improves the segmentation of WMH from T1-w images only.Comment: Conference on Medical Imaging with Deep Learning MIDL 201

Robust training of recurrent neural networks to handle missing data for disease progression modeling

Disease progression modeling (DPM) using longitudinal data is a challenging task in machine learning for healthcare that can provide clinicians with better tools for diagnosis and monitoring of disease. Existing DPM algorithms neglect temporal dependencies among measurements and make parametric assumptions about biomarker trajectories. In addition, they do not model multiple biomarkers jointly and need to align 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. We, therefore, propose a generalized training rule for the most widely used RNN architecture, long short-term memory (LSTM) networks, that can handle missing values in both target and predictor variables. This algorithm is applied for modeling the progression of Alzheimer's disease (AD) using magnetic resonance imaging (MRI) biomarkers. The results show that the proposed LSTM algorithm achieves a lower mean absolute error for prediction of measurements across all considered MRI biomarkers compared to using standard LSTM networks with data imputation or using a regression-based DPM method. Moreover, applying linear discriminant analysis to the biomarkers' values predicted by the proposed algorithm results in a larger area under the receiver operating characteristic curve (AUC) for clinical diagnosis of AD compared to the same alternatives, and the AUC is comparable to state-of-the-art AUCs from a recent cross-sectional medical image classification challenge. This paper shows that built-in handling of missing values in LSTM network training paves the way for application of RNNs in disease progression modeling.Comment: 9 pages, 1 figure, MIDL conferenc

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.Comment: arXiv admin note: substantial text overlap with arXiv:1808.0550

Deep Boosted Regression for MR to CT Synthesis

Attenuation correction is an essential requirement of positron emission tomography (PET) image reconstruction to allow for accurate quantification. However, attenuation correction is particularly challenging for PET-MRI as neither PET nor magnetic resonance imaging (MRI) can directly image tissue attenuation properties. MRI-based computed tomography (CT) synthesis has been proposed as an alternative to physics based and segmentation-based approaches that assign a population-based tissue density value in order to generate an attenuation map. We propose a novel deep fully convolutional neural network that generates synthetic CTs in a recursive manner by gradually reducing the residuals of the previous network, increasing the overall accuracy and generalisability, while keeping the number of trainable parameters within reasonable limits. The model is trained on a database of 20 pre-acquired MRI/CT pairs and a four-fold random bootstrapped validation with a 80:20 split is performed. Quantitative results show that the proposed framework outperforms a state-of-the-art atlas-based approach decreasing the Mean Absolute Error (MAE) from 131HU to 68HU for the synthetic CTs and reducing the PET reconstruction error from 14.3% to 7.2%.Comment: Accepted at SASHIMI201

Label-driven weakly-supervised learning for multimodal deformable image registration

Spatially aligning medical images from different modalities remains a challenging task, especially for intraoperative applications that require fast and robust algorithms. We propose a weakly-supervised, label-driven formulation for learning 3D voxel correspondence from higher-level label correspondence, thereby bypassing classical intensity-based image similarity measures. During training, a convolutional neural network is optimised by outputting a dense displacement field (DDF) that warps a set of available anatomical labels from the moving image to match their corresponding counterparts in the fixed image. These label pairs, including solid organs, ducts, vessels, point landmarks and other ad hoc structures, are only required at training time and can be spatially aligned by minimising a cross-entropy function of the warped moving label and the fixed label. During inference, the trained network takes a new image pair to predict an optimal DDF, resulting in a fully-automatic, label-free, real-time and deformable registration. For interventional applications where large global transformation prevails, we also propose a neural network architecture to jointly optimise the global- and local displacements. Experiment results are presented based on cross-validating registrations of 111 pairs of T2-weighted magnetic resonance images and 3D transrectal ultrasound images from prostate cancer patients with a total of over 4000 anatomical labels, yielding a median target registration error of 4.2 mm on landmark centroids and a median Dice of 0.88 on prostate glands.Comment: Accepted to ISBI 201

Brain volume estimation from post-mortem newborn and fetal MRI

AbstractObjectiveMinimally invasive autopsy using post-mortem magnetic resonance imaging (MRI) is a valid alternative to conventional autopsy in fetuses and infants. Estimation of brain weight is an integral part of autopsy, but manual segmentation of organ volumes on MRI is labor intensive and prone to errors, therefore unsuitable for routine clinical practice. In this paper we aim to show that volumetric measurements of the post-mortem fetal and neonatal brain can be accurately estimated using semi-automatic techniques and a high correlation can be found with the weights measured from conventional autopsy results.MethodsThe brains of 17 newborn subjects, part of Magnetic Resonance Imaging Autopsy Study (MaRIAS), were segmented from post-mortem MR images into cerebrum, cerebellum and brainstem using a publicly available neonate brain atlas and semi-automatic segmentation algorithm. The results of the segmentation were averaged to create a new atlas, which was then used for the automated atlas-based segmentation of 17 MaRIAS fetus subjects. As validation, we manually segmented the MR images from 8 subjects of each cohort and compared them with the automatic ones. The semi-automatic estimation of cerebrum weight was compared with the results of the conventional autopsy.ResultsThe Dice overlaps between the manual and automatic segmentations are 0.991 and 0.992 for cerebrum, 0.873 and 0.888 for cerebellum and 0.819 and 0.815 for brainstem, for newborns and fetuses, respectively. Excellent agreement was obtained between the estimated MR weights and autopsy gold standard ones: mean absolute difference of 5 g and 2% maximum error for the fetus cohort and mean absolute difference of 20 g and 11% maximum error for the newborn one.ConclusionsThe high correlation between the obtained segmentation and autopsy weights strengthens the idea of using post-mortem MRI as an alternative for conventional autopsy of the brain

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 the robust modeling of Alzheimer's disease progression using parametric methods. The proposed method linearly maps the individual's age to a disease progression score (DPS) and jointly fits constrained generalized logistic functions to the longitudinal dynamics of biomarkers as functions of the DPS using M-estimation. Robustness of the estimates is quantified using bootstrapping via Monte Carlo resampling, and the estimated inflection points of the fitted functions are used to temporally order the modeled biomarkers in the disease course. Kernel density estimation is applied to the obtained DPSs for clinical status classification using a Bayesian classifier. Different M-estimators and logistic functions, including a novel type proposed in this study, called modified Stannard, are evaluated on the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for robust modeling of volumetric MRI and PET biomarkers, CSF measurements, as well as cognitive tests. The results show that the modified Stannard function fitted using the logistic loss achieves the best modeling performance with an average normalized MAE of 0.991 across all biomarkers and bootstraps. Applied to the ADNI test set, this model achieves a multiclass AUC of 0.934 in clinical status classification. The obtained results for the proposed model outperform almost all state-of-the-art results in predicting biomarker values and classifying clinical status. Finally, the experiments show that the proposed model, trained using abundant ADNI data, generalizes well to data from the National Alzheimer's Coordinating Center (NACC) with an average normalized MAE of 1.182 and a multiclass AUC of 0.929