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Predicting brain age with deep learning from raw imaging data results in a reliable and heritable biomarker
Open accessAbstract
&NA; Machine learning analysis of neuroimaging data can accurately predict chronological age in healthy people. Deviations from healthy brain ageing have been associated with cognitive impairment and disease. Here we sought to further establish the credentials of ‘brain‐predicted age’ as a biomarker of individual differences in the brain ageing process, using a predictive modelling approach based on deep learning, and specifically convolutional neural networks (CNN), and applied to both pre‐processed and raw T1‐weighted MRI data. Firstly, we aimed to demonstrate the accuracy of CNN brain‐predicted age using a large dataset of healthy adults (N = 2001). Next, we sought to establish the heritability of brain‐predicted age using a sample of monozygotic and dizygotic female twins (N = 62). Thirdly, we examined the test‐retest and multi‐centre reliability of brain‐predicted age using two samples (within‐scanner N = 20; between‐scanner N = 11). CNN brain‐predicted ages were generated and compared to a Gaussian Process Regression (GPR) approach, on all datasets. Input data were grey matter (GM) or white matter (WM) volumetric maps generated by Statistical Parametric Mapping (SPM) or raw data. CNN accurately predicted chronological age using GM (correlation between brain‐predicted age and chronological age r = 0.96, mean absolute error [MAE] = 4.16 years) and raw (r = 0.94, MAE = 4.65 years) data. This was comparable to GPR brain‐predicted age using GM data (r = 0.95, MAE = 4.66 years). Brain‐predicted age was a heritable phenotype for all models and input data (h2 ≥ 0.5). Brain‐predicted age showed high test‐retest reliability (intraclass correlation coefficient [ICC] = 0.90–0.99). Multi‐centre reliability was more variable within high ICCs for GM (0.83–0.96) and poor‐moderate levels for WM and raw data (0.51–0.77). Brain‐predicted age represents an accurate, highly reliable and genetically‐influenced phenotype, that has potential to be used as a biomarker of brain ageing. Moreover, age predictions can be accurately generated on raw T1‐MRI data, substantially reducing computation time for novel data, bringing the process closer to giving real‐time information on brain health in clinical settings. HighlightsChronological age can be accurately predicted using convolutional neural networks.Age predicted is accurate even using raw structural neuroimaging data.Brain‐predicted age can be generated in a clinically applicable timeframe.Brain‐predicted age is significantly heritable.Brain‐predicted age is highly reliable, both within and between scanners.
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MethodHeritability of brain volumes in older adults: the Older Australian Twins Study
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“This is in line with previous research into the heritability of brain volumes (Batouli et al., 2014a; Batouli et al., 2014b) and cognitive function (Bouchard, 2013; Lee et al., 2010).”
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An overview of deep learning in medical imaging focusing on MRI
Lundervold, A. S., & Lundervold, A. (2019) · Zeitschrift für Medizinische Physik · doi:10.1016/j.zemedi.2018.11.002 · Cited by 2,058
“Brain age [273] Chronological age prediction from raw brain T1-MRI data, also testing the heritability of brain-predicted age”
MethodZhou, S. K., Greenspan, H. K., Davatzikos, C. A., Duncan, J. S., van Ginneken, B., Madabhushi, A., Prince, J. L., Rueckert, D., & Summers, R. M. (2021) · Proceedings of the IEEE · doi:10.1109/jproc.2021.3054390 · Cited by 1,373
“In recent years, a large amount of work has been published on deep learning based prediction tasks such as brain age prediction [124], [125], [126], Alzheimer’s disease classification and trajectory modeling [127], [128], [129], [130], and schizophrenia classification [131], [132].”
BackgroundAn overview of deep learning in medical imaging focusing on MRI
Lundervold, A. S., & Lundervold, A. (2018) · NORA - Norwegian Open Research Archives · Cited by 1,012
Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers
Cole, J. H., & Franke, K. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.10.001 · Cited by 939
“In particular, deep learning methods show [344_TD$DIFF]considerable promise [9].”
Self-citationHeterogeneous aging across multiple organ systems and prediction of chronic disease and mortality
Tian, Y. E., Cropley, V., Maier, A. B., Lautenschlager, N. T., Breakspear, M., & Zalesky, A. (2023) · Nature Medicine · doi:10.1038/s41591-023-02296-6 · Cited by 618
Metadata
- Authors
- Cole, J. H., Poudel, R. P. K., Tsagkrasoulis, D., Caan, M. W. A., Steves, C., Spector, T. D., & Montana, G.
- Affiliations
- Imperial College London (GB)
- King's College London (GB)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Montana, Giovanni
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 163
- Pages
- 115-124
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2579617530
- Semantic Scholar
- 5d71c918db224e21982d9eb5ab2359735466959b
- Cited by
- 872
- References
- 72
- Citations by year
- 2026: 91 · 2025: 116 · 2024: 99 · 2023: 106 · 2022: 113 · 2021: 122 · 2020: 92 · 2019: 87 · 2018: 39 · 2017: 6
- FWCI
- 49.85
- Type
- journal article
- Language
- en
- Open access
- green
- arxiv.org
- Licence
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (acceptedVersion)
- arXiv (Cornell University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Warwick Research Archive Portal (University of Warwick) (submittedVersion)
- arXiv (Cornell University)
- Funders
- Wellcome Trust
- Medical Research Council
- European Commision’s Seventh Framework Program (FP7/2007-2013, 259749)
- National Institute for Health Research (NIHR)
- BioResource, Clinical Research Facility
- Biomedical Research Centre
- St Thomas' NHS Foundation Trust
- NIHR Biomedical Research Centre
- Imperial College London from the Medical Research Council (MR/L022141/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- brain age prediction, brain aging, biomarkers, heritability, monozygotic and dizygotic twins, test-retest reliability, convolutional neural networks, gray matter volume, white matter volume, Gaussian process regression, healthy adults, cognitive impairment risk, neuroimaging
- MeSH terms
- Machine Learning, Adolescent, Adult, Aged, Aged, 80 and over, Aging, Brain, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Phenotype, Neural Networks, Computer, Young Adult
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