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DeepAtrophy : Teaching a neural network to detect progressive changes in longitudinal MRI of the hippocampal region in Alzheimer's disease

Dong, Mengjin ; Xie, Long ; Das, Sandhitsu R. ; Wang, Jiancong ; Wisse, Laura E.M. LU orcid ; deFlores, Robin ; Wolk, David A. and Yushkevich, Paul A. (2021) In NeuroImage 243.
Abstract

Measures of change in hippocampal volume derived from longitudinal MRI are a well-studied biomarker of disease progression in Alzheimer's disease (AD) and are used in clinical trials to track therapeutic efficacy of disease-modifying treatments. However, longitudinal MRI change measures based on deformable registration can be confounded by MRI artifacts, resulting in over-estimation or underestimation of hippocampal atrophy. For example, the deformation-based-morphometry method ALOHA (Das et al., 2012) finds an increase in hippocampal volume in a substantial proportion of longitudinal scan pairs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, unexpected, given that the hippocampal gray matter is lost with age and... (More)

Measures of change in hippocampal volume derived from longitudinal MRI are a well-studied biomarker of disease progression in Alzheimer's disease (AD) and are used in clinical trials to track therapeutic efficacy of disease-modifying treatments. However, longitudinal MRI change measures based on deformable registration can be confounded by MRI artifacts, resulting in over-estimation or underestimation of hippocampal atrophy. For example, the deformation-based-morphometry method ALOHA (Das et al., 2012) finds an increase in hippocampal volume in a substantial proportion of longitudinal scan pairs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, unexpected, given that the hippocampal gray matter is lost with age and disease progression. We propose an alternative approach to quantify disease progression in the hippocampal region: to train a deep learning network (called DeepAtrophy) to infer temporal information from longitudinal scan pairs. The underlying assumption is that by learning to derive time-related information from scan pairs, the network implicitly learns to detect progressive changes that are related to aging and disease progression. Our network is trained using two categorical loss functions: one that measures the network's ability to correctly order two scans from the same subject, input in arbitrary order; and another that measures the ability to correctly infer the ratio of inter-scan intervals between two pairs of same-subject input scans. When applied to longitudinal MRI scan pairs from subjects unseen during training, DeepAtrophy achieves greater accuracy in scan temporal ordering and interscan interval inference tasks than ALOHA (88.5% vs. 75.5% and 81.1% vs. 75.0%, respectively). A scalar measure of time-related change in a subject level derived from DeepAtrophy is then examined as a biomarker of disease progression in the context of AD clinical trials. We find that this measure performs on par with ALOHA in discriminating groups of individuals at different stages of the AD continuum. Overall, our results suggest that using deep learning to infer temporal information from longitudinal MRI of the hippocampal region has good potential as a biomarker of disease progression, and hints that combining this approach with conventional deformation-based morphometry algorithms may lead to improved biomarkers in the future.

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author
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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Disease progression, Hippocampus area, Interscan interval, Longitudinal analysis, T1-weighted MRI
in
NeuroImage
volume
243
article number
118514
publisher
Elsevier
external identifiers
  • scopus:85114259961
ISSN
1053-8119
DOI
10.1016/j.neuroimage.2021.118514
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021
id
1063a205-021c-43d6-ad50-2003a829bbc0
date added to LUP
2021-10-13 15:34:49
date last changed
2024-02-20 14:00:48
@article{1063a205-021c-43d6-ad50-2003a829bbc0,
  abstract     = {{<p>Measures of change in hippocampal volume derived from longitudinal MRI are a well-studied biomarker of disease progression in Alzheimer's disease (AD) and are used in clinical trials to track therapeutic efficacy of disease-modifying treatments. However, longitudinal MRI change measures based on deformable registration can be confounded by MRI artifacts, resulting in over-estimation or underestimation of hippocampal atrophy. For example, the deformation-based-morphometry method ALOHA (Das et al., 2012) finds an increase in hippocampal volume in a substantial proportion of longitudinal scan pairs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, unexpected, given that the hippocampal gray matter is lost with age and disease progression. We propose an alternative approach to quantify disease progression in the hippocampal region: to train a deep learning network (called DeepAtrophy) to infer temporal information from longitudinal scan pairs. The underlying assumption is that by learning to derive time-related information from scan pairs, the network implicitly learns to detect progressive changes that are related to aging and disease progression. Our network is trained using two categorical loss functions: one that measures the network's ability to correctly order two scans from the same subject, input in arbitrary order; and another that measures the ability to correctly infer the ratio of inter-scan intervals between two pairs of same-subject input scans. When applied to longitudinal MRI scan pairs from subjects unseen during training, DeepAtrophy achieves greater accuracy in scan temporal ordering and interscan interval inference tasks than ALOHA (88.5% vs. 75.5% and 81.1% vs. 75.0%, respectively). A scalar measure of time-related change in a subject level derived from DeepAtrophy is then examined as a biomarker of disease progression in the context of AD clinical trials. We find that this measure performs on par with ALOHA in discriminating groups of individuals at different stages of the AD continuum. Overall, our results suggest that using deep learning to infer temporal information from longitudinal MRI of the hippocampal region has good potential as a biomarker of disease progression, and hints that combining this approach with conventional deformation-based morphometry algorithms may lead to improved biomarkers in the future.</p>}},
  author       = {{Dong, Mengjin and Xie, Long and Das, Sandhitsu R. and Wang, Jiancong and Wisse, Laura E.M. and deFlores, Robin and Wolk, David A. and Yushkevich, Paul A.}},
  issn         = {{1053-8119}},
  keywords     = {{Alzheimer's disease; Disease progression; Hippocampus area; Interscan interval; Longitudinal analysis; T1-weighted MRI}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{Elsevier}},
  series       = {{NeuroImage}},
  title        = {{DeepAtrophy : Teaching a neural network to detect progressive changes in longitudinal MRI of the hippocampal region in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1016/j.neuroimage.2021.118514}},
  doi          = {{10.1016/j.neuroimage.2021.118514}},
  volume       = {{243}},
  year         = {{2021}},
}