Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Deep-learning cardiac motion analysis for human survival prediction

A preprint version of the article is available at arXiv.

Abstract

Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimizing the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimized for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients, the predictive accuracy (quantified by Harrell’s C-index) was significantly higher (P = 0.0012) for our model C = 0.75 (95% CI: 0.70–0.79) than the human benchmark of C = 0.59 (95% CI: 0.53–0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Segmentation and motion estimation.
Fig. 2: Kaplan–Meier Plots.
Fig. 3: Model interpretation.
Fig. 4: Flow chart showing the design of the study.
Fig. 5: The architecture of the segmentation algorithm.
Fig. 6: The architecture of the prediction network.

Similar content being viewed by others

Data and code availability

Algorithms, motion models and statistical analysis are publicly available on Github under a GNU General Public License (https://github.com/UK-Digital-Heart-Project/4Dsurvival)76. A training simulation is available as a Docker image with an interactive Jupyter notebook hosted on Code Ocean (https://doi.org/10.24433/CO.8519672.v1)77. Personal data are not available due to privacy restrictions.

References

  1. Wang, L., Zhao, G., Cheng, L. & Pietikäinen, M. Machine Learning for Vision-Based Motion Analysis: Theory and Techniques (Springer, London, 2010).

  2. Mei, T. & Zhang, C. Deep learning for intelligent video analysis. Microsoft; https://www.microsoft.com/en-us/research/publication/deep-learning-intelligent-video-analysis/ (2017).

  3. Liang, F., Xie, W. & Yu, Y. Beating heart motion accurate prediction method based on interactive multiple model: an information fusion approach. Biomed. Res. Int. 2017, 1279486 (2017).

    Google Scholar 

  4. Savarese, G. & Lund, L. H. Global public health burden of heart failure. Card. Fail. Rev. 3, 7–11 (2017).

    Article  Google Scholar 

  5. Galie, N. et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur. Heart J. 37, 67–119 (2016).

    Article  Google Scholar 

  6. Puyol-Antón, E. et al. A multimodal spatiotemporal cardiac motion atlas from MR and ultrasound data. Med. Image Anal. 40, 96–110 (2017).

    Article  Google Scholar 

  7. Scatteia, A., Baritussio, A. & Bucciarelli-Ducci, C. Strain imaging using cardiac magnetic resonance. Heart Fail. Rev. 22, 465–476 (2017).

    Article  Google Scholar 

  8. Belkin, M. & Niyogi, P. Laplacian eigenmaps and spectral techniques for embedding and clustering. In Advances in Neural Information Processing Systems 14 (eds Dietterich, T. G. et al.) 585–591 (MIT Press, Cambridge, 2002).

  9. Li, K., Javer, A., Keaveny, E. E. & Brown, A. E. X. Recurrent neural networks with interpretable cells predict and classify worm behaviour. Preprint at https://doi.org/10.1101/222208 (2017).

  10. Walker, J., Doersch, C., Gupta, A. & Hebert, M. An uncertain future: forecasting from static images using variational autoencoders. Preprint at https://arxiv.org/abs/1606.07873 (2016).

  11. Bütepage, J., Black, M., Kragic, D. & Kjellström, H. Deep representation learning for human motion prediction and classification. Preprint at https://arxiv.org/abs/1702.07486 (2017).

  12. Johnson, K. W. et al. Enabling precision cardiology through multiscale biology and systems medicine. JACC Basic Transl. Sci. 2, 311–327 (2017).

    Article  Google Scholar 

  13. Cikes, M. & Solomon, S. D. Beyond ejection fraction: an integrative approach for assessment of cardiac structure and function in heart failure. Eur. Heart J. 37, 1642–1650 (2016).

    Article  Google Scholar 

  14. Ahmad, T. et al. Clinical implications of chronic heart failure phenotypes defined by cluster analysis. J. Am. Coll. Cardiol. 64, 1765–1774 (2014).

    Article  Google Scholar 

  15. Shah, S. J. et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation 131, 269–279 (2015).

    Article  Google Scholar 

  16. Awan, S. E., Sohel, F., Sanfilippo, F. M., Bennamoun, M. & Dwivedi, G. Machine learning in heart failure: ready for prime time. Curr. Opin. Cardiol. 33, 190–195 (2018).

    Article  Google Scholar 

  17. Tripoliti, E. E., Papadopoulos, T. G., Karanasiou, G. S., Naka, K. K. & Fotiadis, D. I. Heart failure: diagnosis, severity estimation and prediction of adverse events through machine learning techniques. Comput. Struct. Biotechnol. J. 15, 26–47 (2017).

    Article  Google Scholar 

  18. Ambale-Venkatesh, B. et al. Cardiovascular event prediction by machine learning: the multi-ethnic study of atherosclerosis. Circ. Res. 121, 1092–1101 (2017).

    Article  Google Scholar 

  19. Yousefi, S. et al. Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models. Sci. Rep. 7, 11707 (2017).

    Article  Google Scholar 

  20. Ching, T., Zhu, X. & Garmire, L. X. Cox-nnet: an artificial neural network method for prognosis prediction of high-throughput omics data. PLoS Comput. Biol. 14, 1–18 (2018).

    Article  Google Scholar 

  21. Katzman, J. et al. DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network. BMC Med. Res. Methodol. 18, 1–12 (2018).

    Article  Google Scholar 

  22. Esteva, A. et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature 542, 115–118 (2017).

    Article  Google Scholar 

  23. Ching, T. et al. Opportunities and obstacles for deep learning in biology and medicine.J. R. Soc. Interface 15, 20170387 (2018).

    Article  Google Scholar 

  24. Litjens, G. et al. A survey on deep learning in medical image analysis. Med. Image Anal. 42, 60–88 (2017).

    Article  Google Scholar 

  25. Shen, D., Wu, G. & Suk, H. I. Deep learning in medical image analysis. Annu. Rev. Biomed. Eng. 19, 221–248 (2017).

    Article  Google Scholar 

  26. Bai, W. et al. Automated cardiovascular magnetic resonance image analysis with fully convolutional networks. J. Cardiovasc. Magn. Reson. 20, 65 (2018).

    Article  Google Scholar 

  27. Piras, P. et al. Morphologically normalized left ventricular motion indicators from MRI feature tracking characterize myocardial infarction. Sci. Rep. 7, 12259 (2017).

    Article  Google Scholar 

  28. Zhang, X. et al. Orthogonal decomposition of left ventricular remodeling in myocardial infarction. Gigascience 6, 1–15 (2017).

    Google Scholar 

  29. Zhang, X. et al. Atlas-based quantification of cardiac remodeling due to myocardial infarction. PLoS ONE 9, e110243 (2014).

    Article  Google Scholar 

  30. Dawes, T. et al. Machine learning of three-dimensional right ventricular motion enables outcome prediction in pulmonary hypertension: a cardiac MR imaging study. Radiology 283, 381–390 (2017).

    Article  Google Scholar 

  31. Rifai, S., Vincent, P., Muller, X., Glorot, X. & Bengio, Y. Contractive auto-encoders: explicit invariance during feature extraction. In Proc. 28th International Conference on Machine Learning, 833–840 (Omnipress, 2011).

  32. Rolfe, J. T. & LeCun, Y. Discriminative recurrent sparse auto-encoders. Preprint at 1301.3775 (2013).

  33. Huang, R., Liu, C., Li, G. & Zhou, J. Adaptive deep supervised autoencoder based image reconstruction for face recognition. Math. Probl. Eng. 2016, 14 (2016).

    Google Scholar 

  34. Du, F., Zhang, J., Ji, N., Hu, J. & Zhang, C. Discriminative representation learning with supervised auto-encoder. Neur. Proc. Lett. https://doi.org/10.1007/s11063-018-9828-2 (2018).

  35. Zaghbani, S., Boujneh, N. & Bouhlel, M. S. Age estimation using deep learning. Comp. Elec. Eng. 68, 337–347 (2018).

    Article  Google Scholar 

  36. Beaulieu-Jones, B. K. & Greene, C. S. Semi-supervised learning of the electronic health record for phenotype stratification. J. Biomed. Inform. 64, 168–178 (2016).

    Article  Google Scholar 

  37. Shakeri, M., Lombaert, H., Tripathi, S. & Kadoury, S. Deep spectral-based shape features for Alzheimer’s disease classification. In International Workshop on Spectral and Shape Analysis in Medical Imaging (eds Reuter, M. et al.) 15–24 (Springer, 2016).

  38. Biffi, C. et al. Learning interpretable anatomical features through deep generative models: Application to cardiac remodeling. In International Conference on Medical Image Computing and Computer-Assisted Intervention Vol. 11071 (eds Frangi, A., Schnabel, J., Davatzikos, C., Alberola-López, C. & Fichtinger, G.) (Springer, 2018).

  39. Dawes, T. J. W., Bello, G. A. & O’Regan, D. P. Multicentre study of machine learning to predict survival in pulmonary hypertension. Open Science Framework https://doi.org/10.17605/OSF.IO/BG6T9 (2018).

  40. Grapsa, J. et al. Echocardiographic and hemodynamic predictors of survival in precapillary pulmonary hypertension: seven-year follow-up. Circ. Cardiovasc. Imaging 8, 45–54 (2015).

    Article  Google Scholar 

  41. Bao, W., Yue, J. & Rao, Y. A deep learning framework for financial time series using stacked autoencoders and long-short term memory. PLoS ONE 12, e0180944 (2017).

    Article  Google Scholar 

  42. Lim, B. & van der Schaar, M. Disease-atlas: navigating disease trajectories with deep learning. Preprint at https://arxiv.org/abs/1803.10254 (2018).

  43. Lee, C., Zame, W. R., Yoon, J. & van der Schaar, M. DeepHit: a deep learning approach to survival analysis with competing risks. In 32nd Association for the Advancement of Artificial Intelligence ( AAAI) Conference (2018).

  44. Gopalan, D., Delcroix, M. & Held, M. Diagnosis of chronic thromboembolic pulmonary hypertension. Eur. Respir. Rev. 26, 160108 (2017).

    Article  Google Scholar 

  45. Kramer, C., Barkhausen, J., Flamm, S., Kim, R. & Nagel, E. Society for cardiovascular magnetic resonance board of trustees task force on standardized protocols. Standardized cardiovascular magnetic resonance (CMR) protocols 2013 update. J. Cardiovasc. Magn. Reson. 15, 91 (2013).

    Article  Google Scholar 

  46. Woodbridge, M., Fagiolo, G. & O’Regan, D. P. MRIdb: medical image management for biobank research. J. Digit. Imaging 26, 886–890 (2013).

    Article  Google Scholar 

  47. Schulz-Menger, J. et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: society for cardiovascular magnetic resonance (SCMR) board of trustees task force on standardized post processing. J. Cardiovasc. Magn. Reson. 15, 35 (2013).

    Article  Google Scholar 

  48. Baggen, V. J. et al. Cardiac magnetic resonance findings predicting mortality in patients with pulmonary arterial hypertension: a systematic review and meta-analysis. Eur. Radiol. 26, 3771–3780 (2016).

    Article  Google Scholar 

  49. Hulshof, H. G. et al. Prognostic value of right ventricular longitudinal strain in patients with pulmonary hypertension: a systematic review and meta-analysis. Eur. Heart J. Cardiovasc. Imaging https://doi.org/10.1093/ehjci/jey120 (2018).

  50. Duan, J. et al. Automatic 3D bi-ventricular segmentation of cardiac images by a shape-constrained multi-task deep learning approach. Preprint at 1808.08578 (2018).

  51. Bai, W. et al. A bi-ventricular cardiac atlas built from 1000+ high resolution MR images of healthy subjects and an analysis of shape and motion. Med. Image Anal. 26, 133–145 (2015).

    Article  Google Scholar 

  52. Shi, W. et al. Temporal sparse free-form deformations. Med. Image Anal. 17, 779–789 (2013).

    Article  Google Scholar 

  53. Rueckert, D. et al. Nonrigid registration using free-form deformations: application to breast MR images. IEEE Trans. Med. Imaging 18, 712–721 (1999).

    Article  Google Scholar 

  54. Bai, W et al. Learning a global descriptor of cardiac motion from a large cohort of 1000+ normal subjects. In 8th International Conference on Functional Imaging and Modeling of the Heart (FIMH’15) Vol. 9126 (Springer, Cham, 2015).

  55. Vincent, P., Larochelle, H., Lajoie, I., Bengio, Y. & Manzagol, P.-A. Stacked denoising autoencoders: learning useful representations in a deep network with a local denoising criterion. J. Mach. Learn. Res. 11, 3371–3408 (2010).

    MathSciNet  MATH  Google Scholar 

  56. Cox, D. Regression models and life-tables. J. R. Stat. Soc. B 34, 187–220 (1972).

    MathSciNet  MATH  Google Scholar 

  57. Srivastava, N., Hinton, G., Krizhevsky, A., Sutskever, I. & Salakhutdinov, R. Dropout: a simple way to prevent neural networks from overfitting. J. Mach. Learn. Res. 15, 1929–1958 (2014).

    MathSciNet  MATH  Google Scholar 

  58. Goodfellow, I., Bengio, Y. & Courville, A. Deep Learning (MIT Press, Cambridge MA, 2016).

  59. Faraggi, D. & Simon, R. A neural network model for survival data. Stat. Med. 14, 73–82 (1995).

    Article  Google Scholar 

  60. Abadi, M. et al. TensorFlow: Large-Scale Machine Learning on Heterogeneous Systems (TensorFlow, 2015); http://download.tensorflow.org/paper/whitepaper2015.pdf

  61. Chollet, F. et al. Keras https://keras.io (2015).

  62. Kennedy, J. & Eberhart, R. Particle swarm optimization. Proc. IEEE Int. Conf. Neural Net. 4, 1942–1948 (1995).

    Article  Google Scholar 

  63. Engelbrecht, A. Fundamentals of Computational Swarm Intelligence (Wiley, Chichester, 2005).

    Google Scholar 

  64. Lorenzo, P. R., Nalepa, J., Kawulok, M., Ramos, L. S. & Pastor, J. R. Particle swarm optimization for hyper-parameter selection in deep neural networks. In Proc. Genetic and Evolutionary Computation Conference, GECCO ‘17, 481–488 (2017).

  65. Claesen, M., Simm, J., Popovic, D. & De Moor, B. Hyperparameter tuning in Python using Optunity.In Proc. International Workshop on Technical Computing for Machine Learning and Mathematical Engineering Vol. 9 (2014).

  66. Harrell, F., Califf, R., Pryor, D., Lee, K. & Rosati, R. Evaluating the yield of medical tests.J. Am. Med. Assoc. 247, 2543–2546 (1982).

    Article  Google Scholar 

  67. Moons, K. et al. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Ann. Intern. Med. 162, W1–W73 (2015).

    Article  Google Scholar 

  68. Harrell, F., Lee, K. & Mark, D. Tutorial in biostatistics: multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat. Med. 15, 361–387 (1996).

    Article  Google Scholar 

  69. Efron, B. Estimating the error rate of a prediction rule: some improvements on cross-validation. J. Am. Stat. Assoc. 78, 316–331 (1983).

    Article  MATH  Google Scholar 

  70. Efron, B. & Tibshirani, R. in An Introduction to the Bootstrap Ch. 17 (Chapman & Hall, New York, 1993).

    Chapter  MATH  Google Scholar 

  71. Smith, G., Seaman, S., Wood, A., Royston, P. & White, I. Correcting for optimistic prediction in small data sets. Am. J. Epidem. 180, 318–324 (2014).

    Article  Google Scholar 

  72. Liu, B. et al. Normal values for myocardial deformation within the right heart measured by feature-tracking cardiovascular magnetic resonance imaging. Int. J. Cardiol. 252, 220–223 (2018).

    Article  Google Scholar 

  73. Gall, H. et al. The Giessen pulmonary hypertension registry: survival in pulmonary hypertension subgroups. J. Heart Lung. Transplant. 36, 957–967 (2017).

    Article  Google Scholar 

  74. Stekhoven, D. J. & Buhlmann, P. missForest–non–parametric missing value imputation for mixed-type data. Bioinformatics 28, 112–118 (2011).

    Article  Google Scholar 

  75. Schroder, M. S., Culhane, A. C., Quackenbush, J. & Haibe-Kains, B. survcomp: an R/Bioconductor package for performance assessment and comparison of survival models. Bioinformatics 27, 3206–3208 (2011).

    Article  Google Scholar 

  76. Bello, G. A. & O’Regan, D. Deep learning cardiac motion analysis for human survival prediction (4Dsurvival) Zenodo https://doi.org/10.5281/zenodo.1451540 (2019).

  77. Bello, G. et al. Deep learning cardiac motion analysis for human survival prediction (4Dsurvival). Code Ocean https://doi.org/10.24433/CO.8519672.v1 (2018).

Download references

Acknowledgements

The research was supported by the British Heart Foundation (NH/17/1/32725, RE/13/4/30184); the National Institute for Health Research Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London; and the Medical Research Council, UK. The TITAN Xp GPU used for this research was kindly donated by the NVIDIA Corporation.

Author information

Authors and Affiliations

Authors

Contributions

G.A.B., C.B. and T.J.W.D. contributed to methodology, software, formal analysis and writing original draft. J.D. contributed to methodology, software and writing original draft; A.d.M. was involved with formal analysis; L.S.G.E.H., J.S.R.G., M.R.W. and S.A.C. were involved in investigation; D.R. contributed to software and supervision; D.P.O. was responsible for conceptualization, supervision, writing (review and editing) and funding acquisition. All authors reviewed the final manuscript.

Corresponding author

Correspondence to Declan P. O’Regan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bello, G.A., Dawes, T.J.W., Duan, J. et al. Deep-learning cardiac motion analysis for human survival prediction. Nat Mach Intell 1, 95–104 (2019). https://doi.org/10.1038/s42256-019-0019-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s42256-019-0019-2

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing