Learning to synthesise the ageing brain without longitudinal data

Brain ageing is a continuous process that is affected by many factors including neurodegenerative diseases. Understanding this process is of great value for both neuroscience research and clinical applications. However, revealing underlying mechanisms is challenging due to the lack of longitudinal data. In this paper, we propose a deep learning-based method that learns to simulate subject-specific brain ageing trajectories without relying on longitudinal data. Our method synthesises aged images using a network conditioned on two clinical variables: age as a continuous variable, and health state, i.e. status of Alzheimer's Disease (AD) for this work, as an ordinal variable. We adopt an adversarial loss to learn the joint distribution of brain appearance and clinical variables and define reconstruction losses that help preserve subject identity. To demonstrate our model, we compare with several approaches using two widely used datasets: Cam-CAN and ADNI. We use ground-truth longitudinal data from ADNI to evaluate the quality of synthesised images. A pre-trained age predictor, which estimates the apparent age of a brain image, is used to assess age accuracy. In addition, we show that we can train the model on Cam-CAN data and evaluate on the longitudinal data from ADNI, indicating the generalisation power of our approach. Both qualitative and quantitative results show that our method can progressively simulate the ageing process by synthesising realistic brain images. The code will be made publicly available at: this https URL.

[1]  Daniel C. Castro,et al.  Deep Structural Causal Models for Tractable Counterfactual Inference , 2020, NeurIPS.

[2]  Swati Sharma,et al.  Evaluation of brain atrophy estimation algorithms using simulated ground-truth data , 2010, Medical Image Anal..

[3]  Daniel H. Mathalon,et al.  Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus , 1995, Neurobiology of Aging.

[4]  Nick C. Fox,et al.  Phenomenological Model of Diffuse Global and Regional Atrophy Using Finite-Element Methods , 2006, IEEE Transactions on Medical Imaging.

[5]  J. Connor,et al.  Iron, brain ageing and neurodegenerative disorders , 2004, Nature Reviews Neuroscience.

[6]  Taku Komura,et al.  Predicting the Evolution of White Matter Hyperintensities in Brain MRI using Generative Adversarial Networks and Irregularity Map , 2019, bioRxiv.

[7]  Taesung Park,et al.  Semantic Image Synthesis With Spatially-Adaptive Normalization , 2019, 2019 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR).

[8]  Simon Osindero,et al.  Conditional Generative Adversarial Nets , 2014, ArXiv.

[9]  Léon Bottou,et al.  Wasserstein Generative Adversarial Networks , 2017, ICML.

[10]  Anders M. Dale,et al.  Increased sensitivity to effects of normal aging and Alzheimer's disease on cortical thickness by adjustment for local variability in gray/white contrast: A multi-sample MRI study , 2009, NeuroImage.

[11]  Dinggang Shen,et al.  Consistent Spatial-Temporal Longitudinal Atlas Construction for Developing Infant Brains , 2016, IEEE Transactions on Medical Imaging.

[12]  Ender Konukoglu,et al.  Visual Feature Attribution Using Wasserstein GANs , 2017, 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition.

[13]  R. Marioni,et al.  Brain age and other bodily ‘ages’: implications for neuropsychiatry , 2018, Molecular Psychiatry.

[14]  Stefan Klöppel,et al.  Estimating the age of healthy subjects from T1-weighted MRI scans using kernel methods: Exploring the influence of various parameters , 2010, NeuroImage.

[15]  Christian Gaser,et al.  Models of the Aging Brain Structure and Individual Decline , 2012, Front. Neuroinform..

[16]  H. Stefánsson,et al.  Deep learning based brain age prediction uncovers associated sequence variants , 2019, bioRxiv.

[17]  Mark W. Woolrich,et al.  Bayesian analysis of neuroimaging data in FSL , 2009, NeuroImage.

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

[19]  Christian Gaser,et al.  Computational Morphometry for Detecting Changes in Brain Structure Due to Development, Aging, Learning, Disease and Evolution , 2009, Front. Neuroinform..

[20]  P. Thomas Fletcher,et al.  Population Shape Regression from Random Design Data , 2007, 2007 IEEE 11th International Conference on Computer Vision.

[21]  Aaron C. Courville,et al.  FiLM: Visual Reasoning with a General Conditioning Layer , 2017, AAAI.

[22]  Hervé Delingette,et al.  A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments , 2019, NeuroImage.

[23]  M. Mattson,et al.  Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States. , 2018, Cell metabolism.

[24]  Brian B. Avants,et al.  Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain , 2008, Medical Image Anal..

[25]  Yoshua Bengio,et al.  Generative Adversarial Nets , 2014, NIPS.

[26]  Daniele Ravì,et al.  Degenerative Adversarial NeuroImage Nets: Generating Images that Mimic Disease Progression , 2019, MICCAI.

[27]  Daniel Rueckert,et al.  Modelling the progression of Alzheimer's disease in MRI using generative adversarial networks , 2018, Medical Imaging.

[28]  Sotirios A. Tsaftaris,et al.  Conditioning Convolutional Segmentation Architectures with Non-Imaging Data , 2019 .

[29]  Katrin Amunts,et al.  Detection of structural changes of the human brain in longitudinally acquired MR images by deformation field morphometry: Methodological analysis, validation and application , 2008, NeuroImage.

[30]  Stephen M. Smith,et al.  Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm , 2001, IEEE Transactions on Medical Imaging.

[31]  C. Jack,et al.  Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease , 1998, Neurology.

[32]  Stuart J. Ritchie,et al.  Brain age predicts mortality , 2017, Molecular Psychiatry.

[33]  Yang Song,et al.  Age Progression/Regression by Conditional Adversarial Autoencoder , 2017, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[34]  Serge J. Belongie,et al.  Arbitrary Style Transfer in Real-Time with Adaptive Instance Normalization , 2017, 2017 IEEE International Conference on Computer Vision (ICCV).

[35]  Joanna M Wardlaw,et al.  What are White Matter Hyperintensities Made of? , 2015, Journal of the American Heart Association.

[36]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[37]  Yong Liu,et al.  Grey-matter volume as a potential feature for the classification of Alzheimer’s disease and mild cognitive impairment: an exploratory study , 2014, Neuroscience Bulletin.

[38]  Muhammad Febrian Rachmadi,et al.  Automatic spatial estimation of white matter hyperintensities evolution in brain MRI using disease evolution predictor deep neural networks , 2020, Medical image analysis.

[39]  Kilian M. Pohl,et al.  Variational AutoEncoder For Regression: Application to Brain Aging Analysis , 2019, MICCAI.

[40]  M. Styner,et al.  Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility , 2014, Pharmacology Biochemistry and Behavior.

[41]  Zhou Wang,et al.  Multiscale structural similarity for image quality assessment , 2003, The Thrity-Seventh Asilomar Conference on Signals, Systems & Computers, 2003.

[42]  Bishesh Khanal,et al.  Simulating Longitudinal Brain MRIs with Known Volume Changes and Realistic Variations in Image Intensity , 2017, Front. Neurosci..

[43]  Cam-CAN Group,et al.  The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data repository: Structural and functional MRI, MEG, and cognitive data from a cross-sectional adult lifespan sample , 2017, NeuroImage.

[44]  Arthur W. Toga,et al.  Automated hippocampal shape analysis predicts the onset of dementia in mild cognitive impairment , 2011, NeuroImage.

[45]  Aaron C. Courville,et al.  Improved Training of Wasserstein GANs , 2017, NIPS.

[46]  Daniel Rueckert,et al.  A spatio-temporal reference model of the aging brain , 2018, NeuroImage.

[47]  Arno Villringer,et al.  Dynamic Properties of Human Brain Structure: Learning-Related Changes in Cortical Areas and Associated Fiber Connections , 2010, The Journal of Neuroscience.

[48]  Yu Zhang,et al.  The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture , 2016, Cerebral cortex.

[49]  Ben Glocker,et al.  TeTrIS: Template Transformer Networks for Image Segmentation With Shape Priors , 2019, IEEE Transactions on Medical Imaging.

[50]  Daniel Rueckert,et al.  Construction of a consistent high-definition spatio-temporal atlas of the developing brain using adaptive kernel regression , 2012, NeuroImage.

[51]  J. Cole,et al.  Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers , 2017, Trends in Neurosciences.

[52]  Joachim M. Buhmann,et al.  Generative Aging of Brain MR-Images and Prediction of Alzheimer Progression , 2019, GCPR.

[53]  Robert Leech,et al.  Prediction of brain age suggests accelerated atrophy after traumatic brain injury , 2015, Annals of neurology.

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

[55]  Chunlan Yang,et al.  Age-Related Gray and White Matter Changes in Normal Adult Brains , 2017, Aging and disease.

[56]  Alzheimer's Disease Neuroimaging Initiative,et al.  Disentangling normal aging from Alzheimer's disease in structural magnetic resonance images , 2015, Neurobiology of Aging.

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

[58]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[59]  Sotirios A. Tsaftaris,et al.  Consistent Brain Ageing Synthesis , 2019, MICCAI.

[60]  拓海 杉山,et al.  “Unpaired Image-to-Image Translation using Cycle-Consistent Adversarial Networks”の学習報告 , 2017 .

[61]  K. Walhovd,et al.  Structural Brain Changes in Aging: Courses, Causes and Cognitive Consequences , 2010, Reviews in the neurosciences.

[62]  Thomas Brox,et al.  U-Net: Convolutional Networks for Biomedical Image Segmentation , 2015, MICCAI.