Moo K. Chung

Jinghan Huang, Moo K. Chung, Anqi Qiu

This study proposes a novel heterogeneous graph convolutional neural network (HGCNN) to handle complex brain fMRI data at regional and across-region levels. We introduce a generic formulation of spectral filters on heterogeneous graphs by introducing the $k-th$ Hodge-Laplacian (HL) operator. In particular, we propose Laguerre polynomial approximations of HL spectral filters and prove that their spatial localization on graphs is related to the polynomial order. Furthermore, based on the bijection property of boundary operators on simplex graphs, we introduce a generic topological graph pooling (TGPool) method that can be used at any dimensional simplices. This study designs HL-node, HL-edge, and HL-HGCNN neural networks to learn signal representation at a graph node, edge levels, and both, respectively. Our experiments employ fMRI from the Adolescent Brain Cognitive Development (ABCD; n=7693) to predict general intelligence. Our results demonstrate the advantage of the HL-edge network over the HL-node network when functional brain connectivity is considered as features. The HL-HGCNN outperforms the state-of-the-art graph neural networks (GNNs) approaches, such as GAT, BrainGNN, dGCN, BrainNetCNN, and Hypergraph NN. The functional connectivity features learned from the HL-HGCNN are meaningful in interpreting neural circuits related to general intelligence.

Moo K. Chung, Shih-Gu Huang, Ian C. Carroll et al.

We introduce an innovative, data-driven topological data analysis (TDA) technique for estimating the state spaces of dynamically changing functional human brain networks at rest. Our method utilizes the Wasserstein distance to measure topological differences, enabling the clustering of brain networks into distinct topological states. This technique outperforms the commonly used k-means clustering in identifying brain network state spaces by effectively incorporating the temporal dynamics of the data without the need for explicit model specification. We further investigate the genetic underpinnings of these topological features using a twin study design, examining the heritability of such state changes. Our findings suggest that the topology of brain networks, particularly in their dynamic state changes, may hold significant hidden genetic information. MATLAB code for the method is available at https://github.com/laplcebeltrami/PH-STAT.

Shih-Gu Huang, Ilwoo Lyu, Anqi Qiu et al.

Heat diffusion has been widely used in brain imaging for surface fairing, mesh regularization and cortical data smoothing. Motivated by diffusion wavelets and convolutional neural networks on graphs, we present a new fast and accurate numerical scheme to solve heat diffusion on surface meshes. This is achieved by approximating the heat kernel convolution using high degree orthogonal polynomials in the spectral domain. We also derive the closed-form expression of the spectral decomposition of the Laplace-Beltrami operator and use it to solve heat diffusion on a manifold for the first time. The proposed fast polynomial approximation scheme avoids solving for the eigenfunctions of the Laplace-Beltrami operator, which is computationally costly for large mesh size, and the numerical instability associated with the finite element method based diffusion solvers. The proposed method is applied in localizing the male and female differences in cortical sulcal and gyral graph patterns obtained from MRI in an innovative way. The MATLAB code is available at http://www.stat.wisc.edu/~mchung/chebyshev.

Jinghan Huang, Qiufeng Chen, Yijun Bian et al.

Graph neural networks (GNNs) have proven effective in capturing relationships among nodes in a graph. This study introduces a novel perspective by considering a graph as a simplicial complex, encompassing nodes, edges, triangles, and $k$-simplices, enabling the definition of graph-structured data on any $k$-simplices. Our contribution is the Hodge-Laplacian heterogeneous graph attention network (HL-HGAT), designed to learn heterogeneous signal representations across $k$-simplices. The HL-HGAT incorporates three key components: HL convolutional filters (HL-filters), simplicial projection (SP), and simplicial attention pooling (SAP) operators, applied to $k$-simplices. HL-filters leverage the unique topology of $k$-simplices encoded by the Hodge-Laplacian (HL) operator, operating within the spectral domain of the $k$-th HL operator. To address computation challenges, we introduce a polynomial approximation for HL-filters, exhibiting spatial localization properties. Additionally, we propose a pooling operator to coarsen $k$-simplices, combining features through simplicial attention mechanisms of self-attention and cross-attention via transformers and SP operators, capturing topological interconnections across multiple dimensions of simplices. The HL-HGAT is comprehensively evaluated across diverse graph applications, including NP-hard problems, graph multi-label and classification challenges, and graph regression tasks in logistics, computer vision, biology, chemistry, and neuroscience. The results demonstrate the model's efficacy and versatility in handling a wide range of graph-based scenarios.

Moo K. Chung, Hernando Ombao

Persistent homology has undergone significant development in recent years. However, one outstanding challenge is to build a coherent statistical inference procedure on persistent diagrams. In this paper, we first present a new lattice path representation for persistent diagrams. We then develop a new exact statistical inference procedure for lattice paths via combinatorial enumerations. The lattice path method is applied to the topological characterization of the protein structures of the COVID-19 virus. We demonstrate that there are topological changes during the conformational change of spike proteins.

Shih-Gu Huang, Moo K. Chung, Anqi Qiu et al.

This paper revisits spectral graph convolutional neural networks (graph-CNNs) given in Defferrard (2016) and develops the Laplace-Beltrami CNN (LB-CNN) by replacing the graph Laplacian with the LB operator. We then define spectral filters via the LB operator on a graph. We explore the feasibility of Chebyshev, Laguerre, and Hermite polynomials to approximate LB-based spectral filters and define an update of the LB operator for pooling in the LBCNN. We employ the brain image data from Alzheimer's Disease Neuroimaging Initiative (ADNI) and demonstrate the use of the proposed LB-CNN. Based on the cortical thickness of the ADNI dataset, we showed that the LB-CNN didn't improve classification accuracy compared to the spectral graph-CNN. The three polynomials had a similar computational cost and showed comparable classification accuracy in the LB-CNN or spectral graph-CNN. Our findings suggest that even though the shapes of the three polynomials are different, deep learning architecture allows us to learn spectral filters such that the classification performance is not dependent on the type of the polynomials or the operators (graph Laplacian and LB operator).

Shih-Gu Huang, Moo K. Chung, Anqi Qiu et al.

Deep neural networks have recently been recognized as one of the powerful learning techniques in computer vision and medical image analysis. Trained deep neural networks need to be generalizable to new data that was not seen before. In practice, there is often insufficient training data available and augmentation is used to expand the dataset. Even though graph convolutional neural network (graph-CNN) has been widely used in deep learning, there is a lack of augmentation methods to generate data on graphs or surfaces. This study proposes two unbiased augmentation methods, Laplace-Beltrami eigenfunction Data Augmentation (LB-eigDA) and Chebyshev polynomial Data Augmentation (C-pDA), to generate new data on surfaces, whose mean is the same as that of real data. LB-eigDA augments data via the resampling of the LB coefficients. In parallel with LB-eigDA, we introduce a fast augmentation approach, C-pDA, that employs a polynomial approximation of LB spectral filters on surfaces. We design LB spectral bandpass filters by Chebyshev polynomial approximation and resample signals filtered via these filters to generate new data on surfaces. We first validate LB-eigDA and C-pDA via simulated data and demonstrate their use for improving classification accuracy. We then employ the brain images of Alzheimer's Disease Neuroimaging Initiative (ADNI) and extract cortical thickness that is represented on the cortical surface to illustrate the use of the two augmentation methods. We demonstrate that augmented cortical thickness has a similar pattern to real data. Second, we show that C-pDA is much faster than LB-eigDA. Last, we show that C-pDA can improve the AD classification accuracy of graph-CNN.

Moo K. Chung

For random field theory based multiple comparison corrections In brain imaging, it is often necessary to compute the distribution of the supremum of a random field. Unfortunately, computing the distribution of the supremum of the random field is not easy and requires satisfying many distributional assumptions that may not be true in real data. Thus, there is a need to come up with a different framework that does not use the traditional statistical hypothesis testing paradigm that requires to compute p-values. With this as a motivation, we can use a different approach called the logistic regression that does not require computing the p-value and still be able to localize the regions of brain network differences. Unlike other discriminant and classification techniques that tried to classify preselected feature vectors, the method here does not require any preselected feature vectors and performs the classification at each edge level.

Moo K. Chung

Image acquisition and segmentation are likely to introduce noise. Further image processing such as image registration and parameterization can introduce additional noise. It is thus imperative to reduce noise measurements and boost signal. In order to increase the signal-to-noise ratio (SNR) and smoothness of data required for the subsequent random field theory based statistical inference, some type of smoothing is necessary. Among many image smoothing methods, Gaussian kernel smoothing has emerged as a de facto smoothing technique among brain imaging researchers due to its simplicity in numerical implementation. Gaussian kernel smoothing also increases statistical sensitivity and statistical power as well as Gausianness. Gaussian kernel smoothing can be viewed as weighted averaging of voxel values. Then from the central limit theorem, the weighted average should be more Gaussian.

Andrey Gritsenko, Martin A. Lindquist, Gregory R. Kirk et al.

A key strength of twin studies arises from the fact that there are two types of twins, monozygotic and dizygotic, that share differing amounts of genetic information. Accurate differentiation of twin types allows efficient inference on genetic influences in a population. However, identification of zygosity is often prone to errors without genotying. In this study, we propose a novel pairwise feature representation to classify the zygosity of twin pairs of resting state functional magnetic resonance images (rs-fMRI). For this, we project an fMRI signal to a set of basis functions and use the projection coefficients as the compact and discriminative feature representation of noisy fMRI. We encode the relationship between twins as the correlation between the new feature representations across brain regions. We employ hill climbing variable selection to identify brain regions that are the most genetically affected. The proposed framework was applied to 208 twin pairs and achieved 94.19% classification accuracy in automatically identifying the zygosity of paired images.

Moo K. Chung, Yanli Wang, Gurong Wu

We present the discrete version of heat kernel smoothing on graph data structure. The method is used to smooth data in an irregularly shaped domains in 3D images. New statistical properties are derived. As an application, we show how to filter out data in the lung blood vessel trees obtained from computed tomography. The method can be further used in representing the complex vessel trees parametrically and extracting the skeleton representation of the trees.

Moo K. Chung, Victoria Vilalta-Gil, Paul J. Rathouz et al.

In many human brain network studies, we do not have sufficient number (n) of images relative to the number (p) of voxels due to the prohibitively expensive cost of scanning enough subjects. Thus, brain network models usually suffer the small-n large-p problem. Such a problem is often remedied by sparse network models, which are usually solved numerically by optimizing L1-penalties. Unfortunately, due to the computational bottleneck associated with optimizing L1-penalties, it is not practical to apply such methods to construct large-scale brain networks at the voxel-level. In this paper, we propose a new scalable sparse network model using cross-correlations that bypass the computational bottleneck. Our model can build sparse brain networks at the voxel level with p > 25000. Instead of using a single sparse parameter that may not be optimal in other studies and datasets, the computational speed gain enables us to analyze the collection of networks at every possible sparse parameter in a coherent mathematical framework via persistent homology. The method is subsequently applied in determining the extent of heritability on a functional brain network at the voxel-level for the first time using twin fMRI.

Moo K. Chung, Anqi Qiu, Seongho Seo et al.

We present a novel kernel regression framework for smoothing scalar surface data using the Laplace-Beltrami eigenfunctions. Starting with the heat kernel constructed from the eigenfunctions, we formulate a new bivariate kernel regression framework as a weighted eigenfunction expansion with the heat kernel as the weights. The new kernel regression is mathematically equivalent to isotropic heat diffusion, kernel smoothing and recently popular diffusion wavelets. Unlike many previous partial differential equation based approaches involving diffusion, our approach represents the solution of diffusion analytically, reducing numerical inaccuracy and slow convergence. The numerical implementation is validated on a unit sphere using spherical harmonics. As an illustration, we have applied the method in characterizing the localized growth pattern of mandible surfaces obtained in CT images from subjects between ages 0 and 20 years by regressing the length of displacement vectors with respect to the template surface.

Moo K. Chung, Jamie L. Hanson, Jieping Ye et al.

Sparse systems are usually parameterized by a tuning parameter that determines the sparsity of the system. How to choose the right tuning parameter is a fundamental and difficult problem in learning the sparse system. In this paper, by treating the the tuning parameter as an additional dimension, persistent homological structures over the parameter space is introduced and explored. The structures are then further exploited in speeding up the computation using the proposed soft-thresholding technique. The topological structures are further used as multivariate features in the tensor-based morphometry (TBM) in characterizing white matter alterations in children who have experienced severe early life stress and maltreatment. These analyses reveal that stress-exposed children exhibit more diffuse anatomical organization across the whole white matter region.

Jia Du, A. Pasha Hosseinbor, Moo K. Chung et al.

We propose a large deformation diffeomorphic metric mapping algorithm to align multiple b-value diffusion weighted imaging (mDWI) data, specifically acquired via hybrid diffusion imaging (HYDI), denoted as LDDMM-HYDI. We then propose a Bayesian model for estimating the white matter atlas from HYDIs. We adopt the work given in Hosseinbor et al. (2012) and represent the q-space diffusion signal with the Bessel Fourier orientation reconstruction (BFOR) signal basis. The BFOR framework provides the representation of mDWI in the q-space and thus reduces memory requirement. In addition, since the BFOR signal basis is orthonormal, the L2 norm that quantifies the differences in the q-space signals of any two mDWI datasets can be easily computed as the sum of the squared differences in the BFOR expansion coefficients. In this work, we show that the reorientation of the $q$-space signal due to spatial transformation can be easily defined on the BFOR signal basis. We incorporate the BFOR signal basis into the LDDMM framework and derive the gradient descent algorithm for LDDMM-HYDI with explicit orientation optimization. Additionally, we extend the previous Bayesian atlas estimation framework for scalar-valued images to HYDIs and derive the expectation-maximization algorithm for solving the HYDI atlas estimation problem. Using real HYDI datasets, we show the Bayesian model generates the white matter atlas with anatomical details. Moreover, we show that it is important to consider the variation of mDWI reorientation due to a small change in diffeomorphic transformation in the LDDMM-HYDI optimization and to incorporate the full information of HYDI for aligning mDWI.