Invertible Network for Classification and Biomarker Selection for ASD

Determining biomarkers for autism spectrum disorder (ASD) is crucial to understanding its mechanisms. Recently deep learning methods have achieved success in the classification task of ASD using fMRI data. However, due to the black-box nature of most deep learning models, it's hard to perform biomarker selection and interpret model decisions. The recently proposed invertible networks can accurately reconstruct the input from its output, and have the potential to unravel the black-box representation. Therefore, we propose a novel method to classify ASD and identify biomarkers for ASD using the connectivity matrix calculated from fMRI as the input. Specifically, with invertible networks, we explicitly determine the decision boundary and the projection of data points onto the boundary. Like linear classifiers, the difference between a point and its projection onto the decision boundary can be viewed as the explanation. We then define the importance as the explanation weighted by the gradient of prediction $w.r.t$ the input, and identify biomarkers based on this importance measure. We perform a regression task to further validate our biomarker selection: compared to using all edges in the connectivity matrix, using the top 10\% important edges we generate a lower regression error on 6 different severity scores. Our experiments show that the invertible network is both effective at ASD classification and interpretable, allowing for discovery of reliable biomarkers.

Graph Neural Network for Interpreting Task-fMRI Biomarkers

Finding the biomarkers associated with ASD is helpful for understanding the underlying roots of the disorder and can lead to earlier diagnosis and more targeted treatment. A promising approach to identify biomarkers is using Graph Neural Networks (GNNs), which can be used to analyze graph structured data, i.e. brain networks constructed by fMRI. One way to interpret important features is through looking at how the classification probability changes if the features are occluded or replaced. The major limitation of this approach is that replacing values may change the distribution of the data and lead to serious errors. Therefore, we develop a 2-stage pipeline to eliminate the need to replace features for reliable biomarker interpretation. Specifically, we propose an inductive GNN to embed the graphs containing different properties of task-fMRI for identifying ASD and then discover the brain regions/sub-graphs used as evidence for the GNN classifier. We first show GNN can achieve high accuracy in identifying ASD. Next, we calculate the feature importance scores using GNN and compare the interpretation ability with Random Forest. Finally, we run with different atlases and parameters, proving the robustness of the proposed method. The detected biomarkers reveal their association with social behaviors. We also show the potential of discovering new informative biomarkers. Our pipeline can be generalized to other graph feature importance interpretation problems.

Efficient Interpretation of Deep Learning Models Using Graph Structure and Cooperative Game Theory: Application to ASD Biomarker Discovery

Discovering imaging biomarkers for autism spectrum disorder (ASD) is critical to help explain ASD and predict or monitor treatment outcomes. Toward this end, deep learning classifiers have recently been used for identifying ASD from functional magnetic resonance imaging (fMRI) with higher accuracy than traditional learning strategies. However, a key challenge with deep learning models is understanding just what image features the network is using, which can in turn be used to define the biomarkers. Current methods extract biomarkers, i.e., important features, by looking at how the prediction changes if "ignoring" one feature at a time. In this work, we go beyond looking at only individual features by using Shapley value explanation (SVE) from cooperative game theory. Cooperative game theory is advantageous here because it directly considers the interaction between features and can be applied to any machine learning method, making it a novel, more accurate way of determining instance-wise biomarker importance from deep learning models. A barrier to using SVE is its computational complexity: $2^N$ given $N$ features. We explicitly reduce the complexity of SVE computation by two approaches based on the underlying graph structure of the input data: 1) only consider the centralized coalition of each feature; 2) a hierarchical pipeline which first clusters features into small communities, then applies SVE in each community. Monte Carlo approximation can be used for large permutation sets. We first validate our methods on the MNIST dataset and compare to human perception. Next, to insure plausibility of our biomarker results, we train a Random Forest (RF) to classify ASD/control subjects from fMRI and compare SVE results to standard RF-based feature importance. Finally, we show initial results on ranked fMRI biomarkers using SVE on a deep learning classifier for the ASD/control dataset.

Multi-path segmentation network

We present a new type of convolutional network for semantic segmentation here. We tested it on several benchmark datasets, including PASCAL VOC, PASCAL Context and Cityscapes. It achieved superior performance compared to state-of-the-art segmentation methods. To increase segmentation accuracy, we design a special structure with multiple columns. The special structure creates much more paths for information flow. Therefore, it has the potential for more accurate segmentation. We propose the idea of multi-path design here, and hope it can help inspire new ideas.

LadderNet: Multi-path networks based on U-Net for medical image segmentation

U-Net has been providing state-of-the-art performance in many medical image segmentation problems. Many modifications have been proposed for U-Net, such as attention U-Net, recurrent residual convolutional U-Net (R2-UNet), and U-Net with residual blocks or blocks with dense connections. However, all these modifications have an encoder-decoder structure with skip connections, and the number of paths for information flow is limited. We propose LadderNet in this paper, which can be viewed as a chain of multiple U-Nets. Instead of only one pair of encoder branch and decoder branch in U-Net, a LadderNet has multiple pairs of encoder-decoder branches, and has skip connections between every pair of adjacent decoder and decoder branches in each level. Inspired by the success of ResNet and R2-UNet, we use modified residual blocks where two convolutional layers in one block share the same weights. A LadderNet has more paths for information flow because of skip connections and residual blocks, and can be viewed as an ensemble of Fully Convolutional Networks (FCN). The equivalence to an ensemble of FCNs improves segmentation accuracy, while the shared weights within each residual block reduce parameter number. Semantic segmentation is essential for retinal disease detection. We tested LadderNet on two benchmark datasets for blood vessel segmentation in retinal images, and achieved superior performance over methods in the literature.

Brain Biomarker Interpretation in ASD Using Deep Learning and fMRI

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Finding the biomarkers associated with ASD is extremely helpful to understand the underlying roots of the disorder and can lead to earlier diagnosis and more targeted treatment. Although Deep Neural Networks (DNNs) have been applied in functional magnetic resonance imaging (fMRI) to identify ASD, understanding the data-driven computational decision making procedure has not been previously explored. Therefore, in this work, we address the problem of interpreting reliable biomarkers associated with identifying ASD; specifically, we propose a 2-stage method that classifies ASD and control subjects using fMRI images and interprets the saliency features activated by the classifier. First, we trained an accurate DNN classifier. Then, for detecting the biomarkers, different from the DNN visualization works in computer vision, we take advantage of the anatomical structure of brain fMRI and develop a frequency-normalized sampling method to corrupt images. Furthermore, in the ASD vs. control subjects classification scenario, we provide a new approach to detect and characterize important brain features into three categories. The biomarkers we found by the proposed method are robust and consistent with previous findings in the literature. We also validate the detected biomarkers by neurological function decoding and comparing with the DNN activation maps.