Anas Z. Abidin

Mutual Connectivity Analysis (MCA) for Nonlinear Functional Connectivity Network Recovery in the Human Brain Using Convergent Cross-Mapping and Non-metric Clustering

We explore a computational framework for functional connectivity analysis in resting-state functional MRI (fMRI) data acquired from the human brain for recovering the underlying network structure and understanding causality between network components. Termed mutual connectivity analysis (MCA), this framework involves two steps, the first of which is to evaluate the pair-wise cross-prediction performance between fMRI pixel time series within the brain. Here, we use a Generalized Radial Basis Functions (GRBF) neural network as a nonlinear time series predictor. In a second step, the underlying network structure is subsequently recovered from the affinity matrix using non-metric network clustering approaches, such as the so-called Louvain method. Finally, we use convergent cross-mapping (CCM) to study causality between different network components. We demonstrate our MCA framework in the problem of recovering the motor cortex network associated with hand movement from resting state fMRI data. Results are compared with a ground truth of active motor cortex regions as identified by a task-based fMRI sequence involving a finger-tapping stimulation experiment. 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.

Using large-scale Granger causality to study changes in brain network properties in the Clinically Isolated Syndrome (CIS) stage of multiple sclerosis

Clinically Isolated Syndrome (CIS) is often considered to be the first neurological episode associated with Multiple sclerosis (MS). At an early stage the inflammatory demyelination occurring in the CNS can manifest as a change in neuronal metabolism, with multiple asymptomatic white matter lesions detected in clinical MRI. Such damage may induce topological changes of brain networks, which can be captured by advanced functional MRI (fMRI) analysis techniques. We test this hypothesis by capturing the effective relationships of 90 brain regions, defined in the Automated Anatomic Labeling (AAL) atlas, using a large-scale Granger Causality (lsGC) framework. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We study for differences in these properties in network graphs obtained for 18 subjects (10 male and 8 female, 9 with CIS and 9 healthy controls). Global network properties captured trending differences with modularity and clustering coefficient (p<0.1). Additionally, local network properties, such as local efficiency and the strength of connections, captured statistically significant (p<0.01) differences in some regions of the inferior frontal and parietal lobe. We conclude that multivariate analysis of fMRI time-series can reveal interesting information about changes occurring in the brain in early stages of MS.

Exploring connectivity with large-scale Granger causality on resting-state functional MRI

BACKGROUND Large-scale Granger causality (lsGC) is a recently developed, resting-state functional MRI (fMRI) connectivity analysis approach that estimates multivariate voxel-resolution connectivity. Unlike most commonly used multivariate approaches, which establish coarse-resolution connectivity by aggregating voxel time-series avoiding an underdetermined problem, lsGC estimates voxel-resolution, fine-grained connectivity by incorporating an embedded dimension reduction. NEW METHOD We investigate application of lsGC on realistic fMRI simulations, modeling smoothing of neuronal activity by the hemodynamic response function and repetition time (TR), and empirical resting-state fMRI data. Subsequently, functional subnetworks are extracted from lsGC connectivity measures for both datasets and validated quantitatively. We also provide guidelines to select lsGC free parameters. RESULTS Results indicate that lsGC reliably recovers underlying network structure with area under receiver operator characteristic curve (AUC) of 0.93 at TR=1.5s for a 10-min session of fMRI simulations. Furthermore, subnetworks of closely interacting modules are recovered from the aforementioned lsGC networks. Results on empirical resting-state fMRI data demonstrate recovery of visual and motor cortex in close agreement with spatial maps obtained from (i) visuo-motor fMRI stimulation task-sequence (Accuracy=0.76) and (ii) independent component analysis (ICA) of resting-state fMRI (Accuracy=0.86). COMPARISON WITH EXISTING METHOD(S) Compared with conventional Granger causality approach (AUC=0.75), lsGC produces better network recovery on fMRI simulations. Furthermore, it cannot recover functional subnetworks from empirical fMRI data, since quantifying voxel-resolution connectivity is not possible as consequence of encountering an underdetermined problem. CONCLUSIONS Functional network recovery from fMRI data suggests that lsGC gives useful insight into connectivity patterns from resting-state fMRI at a multivariate voxel-resolution.

Mutual Connectivity Analysis (MCA) Using Generalized Radial Basis Function Neural Networks for Nonlinear Functional Connectivity Network Recovery in Resting-State Functional MRI

We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 ± 0.037) as well as the underlying network structure (Rand index = 0.87 ± 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.

Nonlinear functional connectivity network recovery in the human brain with mutual connectivity analysis (MCA): convergent cross-mapping and non-metric clustering

We explore a computational framework for functional connectivity analysis in resting-state functional MRI (fMRI) data acquired from the human brain for recovering the underlying network structure and understanding causality between network components. Termed mutual connectivity analysis (MCA), this framework involves two steps, the first of which is to evaluate the pair-wise cross-prediction performance between fMRI pixel time series within the brain. In a second step, the underlying network structure is subsequently recovered from the affinity matrix using non-metric network clustering approaches, such as the so-called Louvain method. Finally, we use convergent cross-mapping (CCM) to study causality between different network components. We demonstrate our MCA framework in the problem of recovering the motor cortex network associated with hand movement from resting state fMRI data. Results are compared with a ground truth of active motor cortex regions as identified by a task-based fMRI sequence involving a finger-tapping stimulation experiment. Our results regarding causation between regions of the motor cortex revealed a significant directional variability and were not readily interpretable in a consistent manner across 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 MCA methodology can extract and visualize valuable information concerning the underlying network structure between different regions of the brain in resting state fMRI.

Volumetric characterization of human patellar cartilage matrix on phase contrast x-ray computed tomography

Phase contrast X-ray computed tomography (PCI-CT) has recently emerged as a novel imaging technique that allows visualization of cartilage soft tissue, subsequent examination of chondrocyte patterns, and their correlation to osteoarthritis. Previous studies have shown that 2D texture features are effective at distinguishing between healthy and osteoarthritic regions of interest annotated in the radial zone of cartilage matrix on PCI-CT images. In this study, we further extend the texture analysis to 3D and investigate the ability of volumetric texture features at characterizing chondrocyte patterns in the cartilage matrix for purposes of classification. Here, we extracted volumetric texture features derived from Minkowski Functionals and gray-level co-occurrence matrices (GLCM) from 496 volumes of interest (VOI) annotated on PCI-CT images of human patellar cartilage specimens. The extracted features were then used in a machine-learning task involving support vector regression to classify ROIs as healthy or osteoarthritic. Classification performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). The best classification performance was observed with GLCM features correlation (AUC = 0.83 ± 0.06) and homogeneity (AUC = 0.82 ± 0.07), which significantly outperformed all Minkowski Functionals (p < 0.05). These results suggest that such quantitative analysis of chondrocyte patterns in human patellar cartilage matrix involving GLCM-derived statistical features can distinguish between healthy and osteoarthritic tissue with high accuracy.

Alteration of brain network topology in HIV-associated neurocognitive disorder: A novel functional connectivity perspective

HIV is capable of invading the brain soon after seroconversion. This ultimately can lead to deficits in multiple cognitive domains commonly referred to as HIV-associated neurocognitive disorders (HAND). Clinical diagnosis of such deficits requires detailed neuropsychological assessment but clinical signs may be difficult to detect during asymptomatic injury of the central nervous system (CNS). Therefore neuroimaging biomarkers are of particular interest in HAND. In this study, we constructed brain connectivity profiles of 40 subjects (20 HIV positive subjects and 20 age-matched seronegative controls) using two different methods: a non-linear mutual connectivity analysis approach and a conventional method based on Pearsons correlation. These profiles were then summarized using graph-theoretic methods characterizing their topological network properties. Standard clinical and laboratory assessments were performed and a battery of neuropsychological (NP) tests was administered for all participating subjects. Based on NP testing, 14 of the seropositive subjects exhibited mild neurologic impairment. Subsequently, we analyzed associations between the network derived measures and neuropsychological assessment scores as well as common clinical laboratory plasma markers (CD4 cell count, HIV RNA) after adjusting for age and gender. Mutual connectivity analysis derived graph-theoretic measures, Modularity and Small Worldness, were significantly (p < 0.05, FDR adjusted) associated with the Executive as well as Overall z-score of NP performance. In contrast, network measures derived from conventional correlation-based connectivity did not yield any significant results. Thus, changes in connectivity can be captured using advanced time-series analysis techniques. The demonstrated associations between imaging-derived graph-theoretic properties of brain networks with neuropsychological performance, provides opportunities to further investigate the evolution of HAND in larger, longitudinal studies. Our analysis approach, involving non-linear time-series analysis in conjunction with graph theory, is promising and it may prove to be useful not only in HAND but also in other neurodegenerative disorders.

Mutual connectivity analysis of resting-state functional MRI data with local models

Abstract Functional connectivity analysis of functional MRI (fMRI) can represent brain networks and reveal insights into interactions amongst different brain regions. However, most connectivity analysis approaches adopted in practice are linear and non‐directional. In this paper, we demonstrate the advantage of a data‐driven, directed connectivity analysis approach called Mutual Connectivity Analysis using Local Models (MCA‐LM) that approximates connectivity by modeling nonlinear dependencies of signal interaction, over more conventionally used approaches, such as Pearsons and partial correlation, Patels conditional dependence measures, etcetera. We demonstrate on realistic simulations of fMRI data that, at long sampling intervals, i.e. high repetition time (TR) of fMRI signals, MCA‐LM performs better than or comparable to correlation‐based methods and Patels measures. However, at fast image acquisition rates corresponding to low TR, MCA‐LM significantly outperforms these methods. This insight is particularly useful in the light of recent advances in fast fMRI acquisition techniques. Methods that can capture the complex dynamics of brain activity, such as MCA‐LM, should be adopted to extract as much information as possible from the improved representation. Furthermore, MCA‐LM works very well for simulations generated at weak neuronal interaction strengths, and simulations modeling inhibitory and excitatory connections as it disentangles the two opposing effects between pairs of regions/voxels. Additionally, we demonstrate that MCA‐LM is capable of capturing meaningful directed connectivity on experimental fMRI data. Such results suggest that it introduces sufficient complexity into modeling fMRI time‐series interactions that simple, linear approaches cannot, while being data‐driven, computationally practical and easy to use. In conclusion, MCA‐LM can provide valuable insights towards better understanding brain activity. HighlightsMutual connectivity analysis‐Local Models (MCA‐LM) is studied for fMRI simulations.It is nonlinear, data‐driven, and outperforms conventionally used methods at low TR.It works well for simulations generated at weak neuronal interaction strengths.It can estimate network well for acyclic graphs and inhibitory‐excitatory links.MCA‐LM can capture robust connectivity measures as seen from real fMRI data results.

Regional autonomy changes in resting-state functional MRI in patients with HIV associated neurocognitive disorder.

In this study, we investigate whether there are discernable changes in influence that brain regions have on themselves once patients show symptoms of HIV Associated Neurocognitive Disorder (HAND) using functional MRI (fMRI). Simple functional connectivity measures, such as correlation cannot reveal such information. To this end, we use mutual connectivity analysis (MCA) with Local Models (LM), which reveals a measure of influence in terms of predictability. Once such measures of interaction are obtained, we train two classifiers to characterize difference in patterns of regional self-influence between healthy subjects and subjects presenting with HAND symptoms. The two classifiers we use are Support Vector Machines (SVM) and Localized Generalized Matrix Learning Vector Quantization (LGMLVQ). Performing machine learning on fMRI connectivity measures is popularly known as multi-voxel pattern analysis (MVPA). By performing such an analysis, we are interested in studying the impact HIV infection has on an individual’s brain. The high area under receiver operating curve (AUC) and accuracy values for 100 different train/test separations using MCA-LM self-influence measures (SVM: mean AUC=0.86, LGMLVQ: mean AUC=0.88, SVM and LGMLVQ: mean accuracy=0.78) compared with standard MVPA analysis using cross-correlation between fMRI time-series (SVM: mean AUC=0.58, LGMLVQ: mean AUC=0.57), demonstrates that self-influence features can be more discriminative than measures of interaction between time-series pairs. Furthermore, our results suggest that incorporating measures of self-influence in MVPA analysis used commonly in fMRI analysis has the potential to provide a performance boost and indicate important changes in dynamics of regions in the brain as a consequence of HIV infection.

MRI tumor segmentation with densely connected 3D CNN.

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 multiscale 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 dataset1 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.