Axel Wismüller

M. Ali Vosoughi, Axel Wismuller

Causal discovery, beyond the inference of a network as a collection of connected dots, offers a crucial functionality in scientific discovery using artificial intelligence. The questions that arise in multiple domains, such as physics, physiology, the strategic decision in uncertain environments with multiple agents, climatology, among many others, have roots in causality and reasoning. It became apparent that many real-world temporal observations are nonlinearly related to each other. While the number of observations can be as high as millions of points, the number of temporal samples can be minimal due to ethical or practical reasons, leading to the curse-of-dimensionality in large-scale systems. This paper proposes a novel method using kernel principal component analysis and pre-images to obtain nonlinear dependencies of multivariate time-series data. We show that our method outperforms state-of-the-art causal discovery methods when the observations are restricted by time and are nonlinearly related. Extensive simulations on both real-world and synthetic datasets with various topologies are provided to evaluate our proposed methods.

Axel Wismüller, M. Ali Vosoughi

The literature manifests that schizophrenia is associated with alterations in brain network connectivity. We investigate whether large-scale Extended Granger Causality (lsXGC) can capture such alterations using resting-state fMRI data. Our method utilizes dimension reduction combined with the augmentation of source time-series in a predictive time-series model for estimating directed causal relationships among fMRI time-series. The lsXGC is a multivariate approach since it identifies the relationship of the underlying dynamic system in the presence of all other time-series. Here lsXGC serves as a biomarker for classifying schizophrenia patients from typical controls using a subset of 62 subjects from the Centers of Biomedical Research Excellence (COBRE) data repository. We use brain connections estimated by lsXGC as features for classification. After feature extraction, we perform feature selection by Kendall's tau rank correlation coefficient followed by classification using a support vector machine. As a reference method, we compare our results with cross-correlation, typically used in the literature as a standard measure of functional connectivity. We cross-validate 100 different training/test (90%/10%) data split to obtain mean accuracy and a mean Area Under the receiver operating characteristic Curve (AUC) across all tested numbers of features for lsXGC. Our results demonstrate a mean accuracy range of [0.767, 0.940] and a mean AUC range of [0.861, 0.983] for lsXGC. The result of lsXGC is significantly higher than the results obtained with the cross-correlation, namely mean accuracy of [0.721, 0.751] and mean AUC of [0.744, 0.860]. Our results suggest the applicability of lsXGC as a potential biomarker for schizophrenia.

Axel Wismuller, M. Ali Vosoughi

We introduce large-scale Augmented Granger Causality (lsAGC) as a method for connectivity analysis in complex systems. The lsAGC algorithm combines dimension reduction with source time-series augmentation and uses predictive time-series modeling for estimating directed causal relationships among time-series. This method is a multivariate approach, since it is capable of identifying the influence of each time-series on any other time-series in the presence of all other time-series of the underlying dynamic system. We quantitatively evaluate the performance of lsAGC on synthetic directional time-series networks with known ground truth. As a reference method, we compare our results with cross-correlation, which is typically used as a standard measure of connectivity in the functional MRI (fMRI) literature. Using extensive simulations for a wide range of time-series lengths and two different signal-to-noise ratios of 5 and 15 dB, lsAGC consistently outperforms cross-correlation at accurately detecting network connections, using Receiver Operator Characteristic Curve (ROC) analysis, across all tested time-series lengths and noise levels. In addition, as an outlook to possible clinical application, we perform a preliminary qualitative analysis of connectivity matrices for fMRI data of Autism Spectrum Disorder (ASD) patients and typical controls, using a subset of 59 subjects of the Autism Brain Imaging Data Exchange II (ABIDE II) data repository. Our results suggest that lsAGC, by extracting sparse connectivity matrices, may be useful for network analysis in complex systems, and may be applicable to clinical fMRI analysis in future research, such as targeting disease-related classification or regression tasks on clinical data.

M. Ali Vosoughi, Axel Wismuller

It has been shown in the literature that marijuana use is associated with changes in brain network connectivity. We propose large-scale Extended Granger Causality (lsXGC) and investigate whether it can capture such changes using resting-state fMRI. This method combines dimension reduction with source time-series augmentation and uses predictive time-series modeling for estimating directed causal relationships among fMRI time-series. It is a multivariate approach, since it is capable of identifying the interdependence of time-series in the presence of all other time-series of the underlying dynamic system. Here, we investigate whether this model can serve as a biomarker for classifying marijuana users from typical controls using 126 adult subjects with a childhood diagnosis of ADHD from the Addiction Connectome Preprocessed Initiative (ACPI) database. We use brain connections estimated by lsXGC as features for classification. After feature extraction, we perform feature selection by Kendall's-tau rank correlation coefficient followed by classification using a support vector machine. As a reference method, we compare our results with cross-correlation, which is typically used in the literature as a standard measure of functional connectivity. Within a cross-validation scheme of 100 different training/test (90%/10%) data splits, we obtain a mean accuracy range of [0.714, 0.985] and a mean Area Under the receiver operating characteristic Curve (AUC) range of [0.779, 0.999] across all tested numbers of features for lsXGC, which is significantly better than results obtained with cross-correlation, namely mean accuracy of [0.728, 0.912] and mean AUC of [0.825, 0.969]. Our results suggest the applicability of lsXGC as a potential biomarker for marijuana use.

M. Ali Vosoughi, Axel Wismuller

Graph topology inference of network processes with co-evolving and interacting time-series is crucial for network studies. Vector autoregressive models (VAR) are popular approaches for topology inference of directed graphs; however, in large networks with short time-series, topology estimation becomes ill-posed. The present paper proposes a novel nonlinearity-preserving topology inference method for directed networks with co-evolving nodal processes that solves the ill-posedness problem. The proposed method, large-scale kernelized Granger causality (lsKGC), uses kernel functions to transform data into a low-dimensional feature space and solves the autoregressive problem in the feature space, then finds the pre-images in the input space to infer the topology. Extensive simulations on synthetic datasets with nonlinear and linear dependencies and known ground-truth demonstrate significant improvement in the Area Under the receiver operating characteristic Curve ( AUC ) of the receiver operating characteristic for network recovery compared to existing methods. Furthermore, tests on real datasets from a functional magnetic resonance imaging (fMRI) study demonstrate 96.3 percent accuracy in diagnosis tasks of schizophrenia patients, which is the highest in the literature with only brain time-series information.

Axel Wismüller, Larry Stockmaster

Objective: To introduce a method for tracking results and utilization of Artificial Intelligence (tru-AI) in radiology. By tracking both large-scale utilization and AI results data, the tru-AI approach is designed to calculate surrogates for measuring important disease-related observational quantities over time, such as the prevalence of intracranial hemorrhage during the COVID-19 pandemic outbreak. Methods: To quantitatively investigate the clinical applicability of the tru-AI approach, we analyzed service requests for automatically identifying intracranial hemorrhage (ICH) on head CT using a commercial AI solution. This software is typically used for AI-based prioritization of radiologists' reading lists for reducing turnaround times in patients with emergent clinical findings, such as ICH or pulmonary embolism.We analyzed data of N=9,421 emergency-setting non-contrast head CT studies at a major US healthcare system acquired from November 1, 2019 through June 2, 2020, and compared two observation periods, namely (i) a pre-pandemic epoch from November 1, 2019 through February 29, 2020, and (ii) a period during the COVID-19 pandemic outbreak, April 1-30, 2020. Results: Although daily CT scan counts were significantly lower during (40.1 +/- 7.9) than before (44.4 +/- 7.6) the COVID-19 outbreak, we found that ICH was more likely to be observed by AI during than before the COVID-19 outbreak (p<0.05), with approximately one daily ICH+ case more than statistically expected. Conclusion: Our results suggest that, by tracking both large-scale utilization and AI results data in radiology, the tru-AI approach can contribute clinical value as a versatile exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.

Axel Wismüller, Adora M. DSouza, Anas Z. Abidin

To gain insight into complex systems it is a key challenge to infer nonlinear causal directional relations from observational time-series data. Specifically, estimating causal relationships between interacting components in large systems with only short recordings over few temporal observations remains an important, yet unresolved problem. Here, we introduce a large-scale Nonlinear Granger Causality (lsNGC) approach for inferring directional, nonlinear, multivariate causal interactions between system components from short high-dimensional time-series recordings. By modeling interactions with nonlinear state-space transformations from limited observational data, lsNGC identifies casual relations with no explicit a priori assumptions on functional interdependence between component time-series in a computationally efficient manner. Additionally, our method provides a mathematical formulation revealing statistical significance of inferred causal relations. We extensively study the ability of lsNGC to recovering network structure from two-node to thirty-four node chaotic time-series systems. Our results suggest that lsNGC captures meaningful interactions from limited observational data, where it performs favorably when compared to traditionally used methods. Finally, we demonstrate the applicability of lsNGC to estimating causality in large, real-world systems by inferring directional nonlinear, multivariate causal relationships among a large number of relatively short time-series acquired from functional Magnetic Resonance Imaging (fMRI) data of the human brain.

Adora M. DSouza, Anas Z. Abidin, Axel Wismüller

Chest x-rays are the most common radiology studies for diagnosing lung and heart disease. Hence, a system for automated pre-reporting of pathologic findings on chest x-rays would greatly enhance radiologists' productivity. To this end, we investigate a deep-learning framework with novel training schemes for classification of different thoracic pathology labels from chest x-rays. We use the currently largest publicly available annotated dataset ChestX-ray14 of 112,120 chest radiographs of 30,805 patients. Each image was annotated with either a 'NoFinding' class, or one or more of 14 thoracic pathology labels. Subjects can have multiple pathologies, resulting in a multi-class, multi-label problem. We encoded labels as binary vectors using k-hot encoding. We study the ResNet34 architecture, pre-trained on ImageNet, where two key modifications were incorporated into the training framework: (1) Stochastic gradient descent with momentum and with restarts using cosine annealing, (2) Variable image sizes for fine-tuning to prevent overfitting. Additionally, we use a heuristic algorithm to select a good learning rate. Learning with restarts was used to avoid local minima. Area Under receiver operating characteristics Curve (AUC) was used to quantitatively evaluate diagnostic quality. Our results are comparable to, or outperform the best results of current state-of-the-art methods with AUCs as follows: Atelectasis:0.81, Cardiomegaly:0.91, Consolidation:0.81, Edema:0.92, Effusion:0.89, Emphysema: 0.92, Fibrosis:0.81, Hernia:0.84, Infiltration:0.73, Mass:0.85, Nodule:0.76, Pleural Thickening:0.81, Pneumonia:0.77, Pneumothorax:0.89 and NoFinding:0.79. Our results suggest that, in addition to using sophisticated network architectures, a good learning rate, scheduler and a robust optimizer can boost performance.

Lele Chen, Yue Wu, Adora M. DSouza et al.

Glioma is one of the most common and aggressive types of primary brain tumors. The accurate segmentation of subcortical brain structures is crucial to the study of gliomas in that it helps the monitoring of the progression of gliomas and aids the evaluation of treatment outcomes. However, the large amount of required human labor makes it difficult to obtain the manually segmented Magnetic Resonance Imaging (MRI) data, limiting the use of precise quantitative measurements in the clinical practice. In this work, we try to address this problem by developing a 3D Convolutional Neural Network~(3D CNN) based model to automatically segment gliomas. The major difficulty of our segmentation model comes with the fact that the location, structure, and shape of gliomas vary significantly among different patients. In order to accurately classify each voxel, our model captures multi-scale contextual information by extracting features from two scales of receptive fields. To fully exploit the tumor structure, we propose a novel architecture that hierarchically segments different lesion regions of the necrotic and non-enhancing tumor~(NCR/NET), peritumoral edema~(ED) and GD-enhancing tumor~(ET). Additionally, we utilize densely connected convolutional blocks to further boost the performance. We train our model with a patch-wise training schema to mitigate the class imbalance problem. The proposed method is validated on the BraTS 2017 dataset and it achieves Dice scores of 0.72, 0.83 and 0.81 for the complete tumor, tumor core and enhancing tumor, respectively. These results are comparable to the reported state-of-the-art results, and our method is better than existing 3D-based methods in terms of compactness, time and space efficiency.

Axel Wismüller, Xixi Wang, Adora M. DSouza et al.

We present a computational framework for analysis and visualization of non-linear functional connectivity in the human brain from resting state functional MRI (fMRI) data for purposes of recovering the underlying network community structure and exploring causality between network components. Our proposed methodology of non-linear mutual connectivity analysis (MCA) involves two computational steps. First, the pair-wise cross-prediction performance between resting state fMRI pixel time series within the brain is evaluated. The underlying network structure is subsequently recovered from the affinity matrix constructed through MCA using non-metric network partitioning/clustering with the so-called Louvain method. We demonstrate our methodology in the task of identifying regions of the motor cortex associated with hand movement on resting state fMRI data acquired from eight slice locations in four subjects. For comparison, we also localized regions of the motor cortex through a task-based fMRI sequence involving a finger-tapping stimulus paradigm. Finally, we integrate convergent cross mapping (CCM) into the first step of MCA for investigating causality between regions of the motor cortex. Results regarding causation between regions of the motor cortex revealed a significant directional variability and were not readily interpretable in a consistent manner across all subjects. However, our results on whole-slice fMRI analysis demonstrate that MCA-based model-free recovery of regions associated with the primary motor cortex and supplementary motor area are in close agreement with localization of similar regions achieved with a task-based fMRI acquisition. Thus, we conclude that our computational framework MCA can extract and visualize valuable information concerning the underlying network structure and causation between different regions of the brain in resting state fMRI.