An Explainable 3D Residual Self-Attention Deep Neural Network FOR Joint Atrophy Localization and Alzheimer's Disease Diagnosis using Structural MRI

Computer-aided early diagnosis of Alzheimer's disease (AD) and its prodromal form mild cognitive impairment (MCI) based on structure Magnetic Resonance Imaging (sMRI) has provided a cost-effective and objective way for early prevention and treatment of disease progression, leading to improved patient care. In this work, we have proposed a novel computer-aided approach for early diagnosis of AD by introducing an explainable 3D Residual Attention Deep Neural Network (3D ResAttNet) for end-to-end learning from sMRI scans. Different from the existing approaches, the novelty of our approach is three-fold: 1) A Residual Self-Attention Deep Neural Network has been proposed to capture local, global and spatial information of MR images to improve diagnostic performance; 2) An explanation method using Gradient-based Localization Class Activation mapping (Grad-CAM) has been introduced to improve the explainable of the proposed method; 3) This work has provided a full end-to-end learning solution for automated disease diagnosis. Our proposed 3D ResAttNet method has been evaluated on a large cohort of subjects from real datasets for two changeling classification tasks (i.e., Alzheimer's disease (AD) vs. Normal cohort (NC) and progressive MCI (pMCI) vs. stable MCI (sMCI)). The experimental results show that the proposed approach has a competitive advantage over the state-of-the-art models in terms of accuracy performance and generalizability. The explainable mechanism in our approach is able to identify and highlight the contribution of the important brain parts (e.g., hippocampus, lateral ventricle and most parts of the cortex) for transparent decisions.

[1]  Xiaogang Wang,et al.  Residual Attention Network for Image Classification , 2017, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[2]  Dinggang Shen,et al.  Landmark‐based deep multi‐instance learning for brain disease diagnosis , 2018, Medical Image Anal..

[3]  Been Kim,et al.  Local Explanation Methods for Deep Neural Networks Lack Sensitivity to Parameter Values , 2018, ICLR.

[4]  Thomas Brox,et al.  Striving for Simplicity: The All Convolutional Net , 2014, ICLR.

[5]  Pierrick Coupé,et al.  Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis , 2017, Multiple sclerosis.

[6]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[7]  F. Gage,et al.  Adult hippocampal neurogenesis and its role in Alzheimer's disease , 2011, Molecular Neurodegeneration.

[8]  Nick C Fox,et al.  The clinical use of structural MRI in Alzheimer disease , 2010, Nature Reviews Neurology.

[9]  Abhishek Das,et al.  Grad-CAM: Visual Explanations from Deep Networks via Gradient-Based Localization , 2016, 2017 IEEE International Conference on Computer Vision (ICCV).

[10]  Ayman El-Baz,et al.  Alzheimer's Disease Diagnostics by a Deeply Supervised Adaptable 3D Convolutional Network , 2016, ArXiv.

[11]  Guigang Zhang,et al.  Deep Learning , 2016, Int. J. Semantic Comput..

[12]  Klaus-Robert Müller,et al.  PatternNet and PatternLRP - Improving the interpretability of neural networks , 2017, ArXiv.

[13]  Andrew Zisserman,et al.  Very Deep Convolutional Networks for Large-Scale Image Recognition , 2014, ICLR.

[14]  Klaus-Robert Müller,et al.  Learning how to explain neural networks: PatternNet and PatternAttribution , 2017, ICLR.

[15]  J. Baron,et al.  In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease , 2001, NeuroImage.

[16]  Nick C Fox,et al.  Automatic classification of MR scans in Alzheimer's disease. , 2008, Brain : a journal of neurology.

[17]  Moo K. Chung,et al.  Spatially augmented LPboosting for AD classification with evaluations on the ADNI dataset , 2009, NeuroImage.

[18]  Hyung-Jeong Yang,et al.  Multimodal learning using convolution neural network and Sparse Autoencoder , 2017, 2017 IEEE International Conference on Big Data and Smart Computing (BigComp).

[19]  Giovanni Montana,et al.  Predicting Alzheimer's disease: a neuroimaging study with 3D convolutional neural networks , 2015, ICPRAM 2015.

[20]  Lukasz Kaiser,et al.  Attention is All you Need , 2017, NIPS.

[21]  Abhinav Gupta,et al.  Non-local Neural Networks , 2017, 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition.

[22]  Daoqiang Zhang,et al.  Relationship Induced Multi-Template Learning for Diagnosis of Alzheimer’s Disease and Mild Cognitive Impairment , 2016, IEEE Transactions on Medical Imaging.

[23]  Chokri Ben Amar,et al.  Classification of Alzheimer’s disease subjects from MRI using hippocampal visual features , 2014, Multimedia Tools and Applications.

[24]  Jeroen van der Grond,et al.  Alzheimer Disease and Behavioral Variant Frontotemporal Dementia: Automatic Classification Based on Cortical Atrophy for Single-Subject Diagnosis. , 2016, Radiology.

[25]  M. Gilardi,et al.  Magnetic resonance imaging biomarkers for the early diagnosis of Alzheimer's disease: a machine learning approach , 2015, Front. Neurosci..

[26]  Yun Fu,et al.  Guided Attention Inference Network , 2020, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[27]  Jean-Michel Morel,et al.  A non-local algorithm for image denoising , 2005, 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05).

[28]  Yalin Wang,et al.  Disease classification with hippocampal shape invariants , 2009, Hippocampus.

[29]  Assawin Gongvatana,et al.  Brain ventricular volume and cerebrospinal fluid biomarkers of Alzheimer's disease. , 2010, Journal of Alzheimer's disease : JAD.

[30]  Yi Yang,et al.  Adversarial Complementary Learning for Weakly Supervised Object Localization , 2018, 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition.

[31]  Ove Almkvist,et al.  Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment , 2003, NeuroImage.

[32]  Colin Studholme,et al.  Deformation-based mapping of volume change from serial brain MRI in the presence of local tissue contrast change , 2006, IEEE Transactions on Medical Imaging.

[33]  Daoqiang Zhang,et al.  Multimodal classification of Alzheimer's disease and mild cognitive impairment , 2011, NeuroImage.

[34]  Han Zhang,et al.  Self-Attention Generative Adversarial Networks , 2018, ICML.

[35]  Shihui Ying,et al.  Multimodal Neuroimaging Feature Learning With Multimodal Stacked Deep Polynomial Networks for Diagnosis of Alzheimer's Disease , 2018, IEEE Journal of Biomedical and Health Informatics.

[36]  Christopher Hunt,et al.  Notes on the OpenSURF Library , 2009 .

[37]  Mariusz Bojarski,et al.  VisualBackProp: efficient visualization of CNNs , 2018 .

[38]  Hanane Allioui,et al.  Utilization of a convolutional method for Alzheimer disease diagnosis , 2020, Machine Vision and Applications.

[39]  Dinggang Shen,et al.  Hierarchical Fully Convolutional Network for Joint Atrophy Localization and Alzheimer's Disease Diagnosis Using Structural MRI , 2020, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[40]  Juha Koikkalainen,et al.  Multi-template tensor-based morphometry: Application to analysis of Alzheimer's disease , 2011, NeuroImage.

[41]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[42]  Mohamad Habes,et al.  Deep Ordinal Ranking for Multi-Category Diagnosis of Alzheimer's Disease using Hippocampal MRI data , 2017, ArXiv.

[43]  Klaus-Robert Müller,et al.  iNNvestigate neural networks! , 2018, J. Mach. Learn. Res..

[44]  Prospero C. Naval,et al.  DemNet: A Convolutional Neural Network for the detection of Alzheimer's Disease and Mild Cognitive Impairment , 2016, 2016 IEEE Region 10 Conference (TENCON).

[45]  Alan C. Evans,et al.  Enhancement of MR Images Using Registration for Signal Averaging , 1998, Journal of Computer Assisted Tomography.

[46]  Alexander Binder,et al.  Explaining nonlinear classification decisions with deep Taylor decomposition , 2015, Pattern Recognit..

[47]  Dinggang Shen,et al.  COMPARE: Classification of Morphological Patterns Using Adaptive Regional Elements , 2007, IEEE Transactions on Medical Imaging.

[48]  Shie Mannor,et al.  A Tutorial on the Cross-Entropy Method , 2005, Ann. Oper. Res..

[49]  Dinggang Shen,et al.  Robust Deformable-Surface-Based Skull-Stripping for Large-Scale Studies , 2011, MICCAI.

[50]  Christos Davatzikos,et al.  A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer's disease and its prodromal stages , 2017, NeuroImage.

[51]  Chokri Ben Amar,et al.  Alzheimer's disease diagnosis on structural MR images using circular harmonic functions descriptors on hippocampus and posterior cingulate cortex , 2015, Comput. Medical Imaging Graph..

[52]  Geoffrey E. Hinton,et al.  ImageNet classification with deep convolutional neural networks , 2012, Commun. ACM.

[53]  Sanjay Ranka,et al.  Visual Explanations From Deep 3D Convolutional Neural Networks for Alzheimer's Disease Classification , 2018, AMIA.

[54]  Sidong Liu,et al.  Early diagnosis of Alzheimer's disease with deep learning , 2014, 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI).

[55]  Alexander Binder,et al.  On Pixel-Wise Explanations for Non-Linear Classifier Decisions by Layer-Wise Relevance Propagation , 2015, PloS one.

[56]  Bolei Zhou,et al.  Learning Deep Features for Discriminative Localization , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[57]  Yi Yang,et al.  Self-produced Guidance for Weakly-supervised Object Localization , 2018, ECCV.

[58]  Jenny Benois-Pineau,et al.  Classification of sMRI for AD Diagnosis with Convolutional Neuronal Networks: A Pilot 2-D+ \epsilon Study on ADNI , 2017, MMM.

[59]  Karl J. Friston,et al.  Voxel-based morphometry of the human brain: Methods and applications , 2005 .

[60]  Marie Chupin,et al.  Multidimensional classification of hippocampal shape features discriminates Alzheimer's disease and mild cognitive impairment from normal aging , 2009, NeuroImage.

[61]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[62]  Rob Fergus,et al.  Visualizing and Understanding Convolutional Networks , 2013, ECCV.

[63]  Karl J. Friston,et al.  Why Voxel-Based Morphometry Should Be Used , 2001, NeuroImage.

[64]  H. Benali,et al.  Support vector machine-based classification of Alzheimer’s disease from whole-brain anatomical MRI , 2009, Neuroradiology.

[65]  Seong-Whan Lee,et al.  Hierarchical feature representation and multimodal fusion with deep learning for AD/MCI diagnosis , 2014, NeuroImage.