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Conditional VAEs for Confound Removal and Normative Modelling of Neurodegenerative Diseases

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Medical Image Computing and Computer Assisted Intervention – MICCAI 2022 (MICCAI 2022)

Part of the book series: Lecture Notes in Computer Science ((LNCS,volume 13431))

Abstract

Understanding pathological mechanisms for heterogeneous brain disorders is a difficult challenge. Normative modelling provides a statistical description of the ‘normal’ range that can be used at subject level to detect deviations, which relate to disease presence, disease severity or disease subtype. Here we trained a conditional Variational Autoencoder (cVAE) on structural MRI data from healthy controls to create a normative model conditioned on confounding variables such as age. The cVAE allows us to use deep learning to identify complex relationships that are independent of these confounds which might otherwise inflate pathological effects. We propose a latent deviation metric and use it to quantify deviations in individual subjects with neurological disorders and, in an independent Alzheimer’s disease dataset, subjects with varying degrees of pathological ageing. Our model is able to identify these disease cohorts as deviations from the normal brain in such a way that reflect disease severity.

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Notes

  1. 1.

    Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

References

  1. Alemi, A.A., Fischer, I., Dillon, J.V., Murphy, K.: Deep variational information bottleneck. CoRR abs/1612.00410 (2016). http://arxiv.org/abs/1612.00410

  2. Apostolova, L., et al.: Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (mci), and Alzheimer disease. Alzheimer Dis. Assoc. Disord. 26, 17–27 (2012)

    Article  Google Scholar 

  3. Baron, J.C., et al.: In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer’s disease. NeuroImage 14, 298–309 (2001)

    Article  Google Scholar 

  4. Bojanowski, P., Joulin, A., Lopez-Paz, D., Szlam, A.: Optimizing the latent space of generative networks (2017)

    Google Scholar 

  5. Desikan, R.S., et al.: An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31(3), 968–980 (2006)

    Article  Google Scholar 

  6. Dincer, A.B., Janizek, J.D., Lee, S.I.: Adversarial deconfounding autoencoder for learning robust gene expression embeddings. Bioinformatics 36, 573–582 (2020)

    Article  Google Scholar 

  7. Elad, D., et al.: Improving the predictive potential of diffusion MRI in schizophrenia using normative models-towards subject-level classification. Hum. Brain Mapp. 42, 4658–4670 (2021)

    Article  Google Scholar 

  8. Erus, G., et al.: Imaging Patterns of Brain Development and their Relationship to Cognition. Cerebral Cortex 25(6), 1676–1684 (2014)

    Article  Google Scholar 

  9. Johnson, W.E., Li, C., Rabinovic, A.: Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8(1), 118–127 (2006)

    Article  Google Scholar 

  10. Kia, S.M., et al.: Hierarchical Bayesian regression for multi-site normative modeling of neuroimaging data. In: Martel, A.L., et al. (eds.) MICCAI 2020. LNCS, vol. 12267, pp. 699–709. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-59728-3_68

    Chapter  Google Scholar 

  11. Kingma, D., Welling, M.: Auto-encoding variational Bayes (12 2014)

    Google Scholar 

  12. Kirichenko, P., Izmailov, P., Wilson, A.G.: Why normalizing flows fail to detect out-of-distribution data (2020). https://doi.org/10.48550/ARXIV.2006.08545. https://arxiv.org/abs/2006.08545

  13. Kostro, D., et al.: Correction of inter-scanner and within-subject variance in structural MRI based automated diagnosing. NeuroImage 98, 405–415 (2014)

    Article  Google Scholar 

  14. Kumar, A., Sattigeri, P., Balakrishnan, A.: Variational inference of disentangled latent concepts from unlabeled observations. CoRR abs/1711.00848 (2017). http://arxiv.org/abs/1711.00848

  15. Kumar, S.: Normvae: normative modeling on neuroimaging data using variational autoencoders. arXiv e-prints arXiv:2110.04903 (2021)

  16. Marquand, A., Kia, S.M., Zabihi, M., Wolfers, T., Buitelaar, J., Beckmann, C.: Conceptualizing mental disorders as deviations from normative functioning. Mol. Psychiatry 24, 1415–1424 (2019)

    Article  Google Scholar 

  17. Marquand, A.F., Rezek, I., Buitelaar, J., Beckmann, C.F.: Understanding heterogeneity in clinical cohorts using normative models: beyond case-control studies. Biol. Psychiat. 80(7), 552–561 (2016)

    Article  Google Scholar 

  18. Mathieu, E., Rainforth, T., Siddharth, N., Teh, Y.W.: Disentangling disentanglement in variational autoencoders (2019)

    Google Scholar 

  19. Miller, M.I., et al.: Amygdala atrophy in symptomatic Alzheimer’s disease based on diffeomorphometry: the biocard cohort. Neurobiol. Aging 36, S3–S10 (2015)

    Article  Google Scholar 

  20. Ordaz, S.J., Foran, W., Velanova, K., Luna, B.: Longitudinal growth curves of brain function underlying inhibitory control through adolescence. J. Neurosci. 33(46), 18109–18124 (2013)

    Article  Google Scholar 

  21. Petersen, R., et al.: Alzheimer’s disease neuroimaging initiative (ADNI): clinical characterization. Neurology 74(3), 201–209 (2010). https://doi.org/10.1212/wnl.0b013e3181cb3e25,https://europepmc.org/articles/PMC2809036

  22. Pinaya, W., et al.: Using normative modelling to detect disease progression in mild cognitive impairment and Alzheimer’s disease in a cross-sectional multi-cohort study. Sci. Rep. 11, 1–13 (2021)

    Article  Google Scholar 

  23. Pinaya, W., Mechelli, A., Sato, J.: Using deep autoencoders to identify abnormal brain structural patterns in neuropsychiatric disorders: a large-scale multi-sample study. Hum. Brain Map. 40, 944–954 (2018)

    Article  Google Scholar 

  24. Rao, A., Monteiro, J.M., Mourao-Miranda, J.: Predictive modelling using neuroimaging data in the presence of confounds. Neuroimage 150, 23–49 (2017)

    Article  Google Scholar 

  25. Rolinek, M., Zietlow, D., Martius, G.: Variational autoencoders pursue PCA directions (by accident) (2019)

    Google Scholar 

  26. Sohn, K., Lee, H., Yan, X.: Learning structured output representation using deep conditional generative models. In: Advances in Neural Information Processing Systems, vol. 28. Curran Associates, Inc. (2015)

    Google Scholar 

  27. Sudlow, C., et al.: UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015)

    Google Scholar 

  28. Trippe, B.L., Turner, R.E.: Conditional density estimation with Bayesian normalising flows (2018). https://doi.org/10.48550/ARXIV.1802.04908, https://arxiv.org/abs/1802.04908

  29. Wang, H., Wu, Z., Xing, E.P.: Removing confounding factors associated weights in deep neural networks improves the prediction accuracy for healthcare applications. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 24, 54–65 (2019)

    Google Scholar 

  30. Wolfers, T., Beckmann, C.F., Hoogman, M., Buitelaar, J.K., Franke, B., Marquand, A.F.: Individual differences v. the average patient: mapping the heterogeneity in ADHD using normative models. Psychol. Med. 50(2), 314–323 (2019)

    Article  Google Scholar 

  31. Zhao, Q., Adeli, E., Pohl, K.: Training confounder-free deep learning models for medical applications. Nat. Commun. 11, 1–9 (2020)

    Article  Google Scholar 

  32. Ziegler, G., Ridgway, G., Dahnke, R., Gaser, C.: Individualized gaussian process-based prediction and detection of local and global gray matter abnormalities in elderly subjects. NeuroImage 97, 1–9 (2014)

    Article  Google Scholar 

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Acknowledgements

This work is supported by the EPSRC-funded UCL Centre for Doctoral Training in Intelligent, Integrated Imaging in Healthcare (i4health) and the Department of Health’s NIHR-funded Biomedical Research Centre at University College London Hospitals.

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Correspondence to Ana Lawry Aguila .

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Lawry Aguila, A., Chapman, J., Janahi, M., Altmann, A. (2022). Conditional VAEs for Confound Removal and Normative Modelling of Neurodegenerative Diseases. In: Wang, L., Dou, Q., Fletcher, P.T., Speidel, S., Li, S. (eds) Medical Image Computing and Computer Assisted Intervention – MICCAI 2022. MICCAI 2022. Lecture Notes in Computer Science, vol 13431. Springer, Cham. https://doi.org/10.1007/978-3-031-16431-6_41

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  • DOI: https://doi.org/10.1007/978-3-031-16431-6_41

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