Automatic Brain Tumor Segmentation using Cascaded Anisotropic Convolutional Neural Networks

A cascade of fully convolutional neural networks is proposed to segment multi-modal Magnetic Resonance (MR) images with brain tumor into background and three hierarchical regions: whole tumor, tumor core and enhancing tumor core. The cascade is designed to decompose the multi-class segmentation problem into a sequence of three binary segmentation problems according to the subregion hierarchy. The whole tumor is segmented in the first step and the bounding box of the result is used for the tumor core segmentation in the second step. The enhancing tumor core is then segmented based on the bounding box of the tumor core segmentation result. Our networks consist of multiple layers of anisotropic and dilated convolution filters, and they are combined with multi-view fusion to reduce false positives. Residual connections and multi-scale predictions are employed in these networks to boost the segmentation performance. Experiments with BraTS 2017 validation set show that the proposed method achieved average Dice scores of 0.7859, 0.9050, 0.8378 for enhancing tumor core, whole tumor and tumor core, respectively. The corresponding values for BraTS 2017 testing set were 0.7831, 0.8739, and 0.7748, respectively.Comment: 12 pages, 5 figures. MICCAI Brats Challenge 201

Disease Progression Modeling and Prediction through Random Effect Gaussian Processes and Time Transformation

The development of statistical approaches for the joint modelling of the temporal changes of imaging, biochemical, and clinical biomarkers is of paramount importance for improving the understanding of neurodegenerative disorders, and for providing a reference for the prediction and quantification of the pathology in unseen individuals. Nonetheless, the use of disease progression models for probabilistic predictions still requires investigation, for example for accounting for missing observations in clinical data, and for accurate uncertainty quantification. We tackle this problem by proposing a novel Gaussian process-based method for the joint modeling of imaging and clinical biomarker progressions from time series of individual observations. The model is formulated to account for individual random effects and time reparameterization, allowing non-parametric estimates of the biomarker evolution, as well as high flexibility in specifying correlation structure, and time transformation models. Thanks to the Bayesian formulation, the model naturally accounts for missing data, and allows for uncertainty quantification in the estimate of evolutions, as well as for probabilistic prediction of disease staging in unseen patients. The experimental results show that the proposed model provides a biologically plausible description of the evolution of Alzheimer's pathology across the whole disease time-span as well as remarkable predictive performance when tested on a large clinical cohort with missing observations.Comment: 13 pages, 2 figure

Part-to-whole Registration of Histology and MRI using Shape Elements

Image registration between histology and magnetic resonance imaging (MRI) is a challenging task due to differences in structural content and contrast. Too thick and wide specimens cannot be processed all at once and must be cut into smaller pieces. This dramatically increases the complexity of the problem, since each piece should be individually and manually pre-aligned. To the best of our knowledge, no automatic method can reliably locate such piece of tissue within its respective whole in the MRI slice, and align it without any prior information. We propose here a novel automatic approach to the joint problem of multimodal registration between histology and MRI, when only a fraction of tissue is available from histology. The approach relies on the representation of images using their level lines so as to reach contrast invariance. Shape elements obtained via the extraction of bitangents are encoded in a projective-invariant manner, which permits the identification of common pieces of curves between two images. We evaluated the approach on human brain histology and compared resulting alignments against manually annotated ground truths. Considering the complexity of the brain folding patterns, preliminary results are promising and suggest the use of characteristic and meaningful shape elements for improved robustness and efficiency.Comment: Paper accepted at ICCV Workshop (Bio-Image Computing

The value of hippocampal and temporal horn volumes and rates of change in predicting future conversion to AD.

Hippocampal pathology occurs early in Alzheimer disease (AD), and atrophy, measured by volumes and volume changes, may predict which subjects will develop AD. Measures of the temporal horn (TH), which is situated adjacent to the hippocampus, may also indicate early changes in AD. Previous studies suggest that these metrics can predict conversion from amnestic mild cognitive impairment (MCI) to AD with conversion and volume change measured concurrently. However, the ability of these metrics to predict future conversion has not been investigated. We compared the abilities of hippocampal, TH, and global measures to predict future conversion from MCI to AD. TH, hippocampi, whole brain, and ventricles were measured using baseline and 12-month scans. Boundary shift integral was used to measure the rate of change. We investigated the prediction of conversion between 12 and 24 months in subjects classified as MCI from baseline to 12 months. All measures were predictive of future conversion. Local and global rates of change were similarly predictive of conversion. There was evidence that the TH expansion rate is more predictive than the hippocampal atrophy rate (P=0.023) and that the TH expansion rate is more predictive than the TH volume (P=0.036). Prodromal atrophy rates may be useful predictors of future conversion to sporadic AD from amnestic MCI

Elastic Registration of Geodesic Vascular Graphs

Vascular graphs can embed a number of high-level features, from morphological parameters, to functional biomarkers, and represent an invaluable tool for longitudinal and cross-sectional clinical inference. This, however, is only feasible when graphs are co-registered together, allowing coherent multiple comparisons. The robust registration of vascular topologies stands therefore as key enabling technology for group-wise analyses. In this work, we present an end-to-end vascular graph registration approach, that aligns networks with non-linear geometries and topological deformations, by introducing a novel overconnected geodesic vascular graph formulation, and without enforcing any anatomical prior constraint. The 3D elastic graph registration is then performed with state-of-the-art graph matching methods used in computer vision. Promising results of vascular matching are found using graphs from synthetic and real angiographies. Observations and future designs are discussed towards potential clinical applications

Spatial calibration of a 2D/3D ultrasound using a tracked needle

PURPOSE: Spatial calibration between a 2D/3D ultrasound and a pose tracking system requires a complex and time-consuming procedure. Simplifying this procedure without compromising the calibration accuracy is still a challenging problem. METHOD: We propose a new calibration method for both 2D and 3D ultrasound probes that involves scanning an arbitrary region of a tracked needle in different poses. This approach is easier to perform than most alternative methods that require a precise alignment between US scans and a calibration phantom. RESULTS: Our calibration method provides an average accuracy of 2.49 mm for a 2D US probe with 107 mm scanning depth, and an average accuracy of 2.39 mm for a 3D US with 107 mm scanning depth. CONCLUSION: Our method proposes a unified calibration framework for 2D and 3D probes using the same phantom object, work-flow, and algorithm. Our method significantly improves the accuracy of needle-based methods for 2D US probes as well as extends its use for 3D US probes

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