Evidence map›Paper›PMID 34450261›Full record

ArticleNeuroImage2021

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

Mengjin Dong, Long Xie, Sandhitsu R Das, Jiancong Wang, Laura E M Wisse, Robin deFlores, David A Wolk, Paul A Yushkevich, Alzheimer's Disease Neuroimaging Initiative

Open access · goldAbstract read
In one paragraph

Article in NeuroImage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Learning General-Purpose Biomedical Volume Representations using Randomized Synthesis.... International Conference on Learning Representations · 2025
    Article
  4. Learning-based inference of longitudinal image changes: Applications in embryo development, wound healing, and aging brain.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Beyond Macrostructure: Is There a Role for Radiomics Analysis in Neuroimaging ?Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 3 countries.

Mengjin DongPenn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: dmengjin@gmail.com.
Long XiePenn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Sandhitsu R DasPenn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States; Penn Memory Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Jiancong WangPenn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States.
Laura E M WissePenn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States; Department of Diagnostic Radiology, Lund University, Lund, Sweden.
Robin deFloresDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States; Penn Memory Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States; Institut National de la Santé et de la Recherche Médicale (INSERM), Caen, France.
David A WolkDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States; Penn Memory Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Paul A YushkevichPenn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Alzheimer's Disease Neuroimaging Initiative
University of Pennsylvania · USPenn Center for AIDS Research · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8M
Ex Vivo Imaging of the Aging Brain to Discover Morphology/Pathology AssociationsR01AG056014 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Paul A. Yushkevich · 2017 to 2026
$4.5M
Modulators of Medial Temporal Lobe Subregion Structure and Function in Normal and Pathological AgingR01AG055005 · NIA · UNIVERSITY OF PENNSYLVANIA · PI WOLK, DAVID A · 2017 to 2021
$3.3M
Improving Transition Outcomes through Accessible Health IT and Caregiver SupportR01AG039474 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIETTE, JOHN D. · 2011 to 2015
$2.7M
Improving the sensitivity and specificity of MRI-based biomarkers in Alzheimer's diseaseRF1AG069474 · NIA · UNIVERSITY OF PENNSYLVANIA · PI WOLK, DAVID A, YUSHKEVICH, PAUL A. · 2021 to 2021
$2.1M
Optimized Arterial Spin Labeling MRI in Mild Cognitive ImpairmentR01AG040271 · NIA · UNIVERSITY OF PENNSYLVANIA · PI WOLK, DAVID A · 2012 to 2016
$2.0M
Improving the sensitivity and specificity of MRI-based biomarkers in Alzheimer's diseaseR01AG069474 · NIA · UNIVERSITY OF PENNSYLVANIA · PI WOLK, DAVID A, YUSHKEVICH, PAUL A. · 2024 to 2025
$1.4M
NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG039474NIA NIH HHS R01 AG040271NIA NIH HHS R01 AG055005NIA NIH HHS R01 AG056014NIA NIH HHS R01 AG069474NIA NIH HHS RF1 AG069474NIA NIH HHS U01 AG024904
6 · The paper itself

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 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.

Indexed as

Neural Networks, ComputerAgedAged, 80 and overAlgorithmsAlzheimer DiseaseAtrophyBiomarkersCognitive DysfunctionDisease ProgressionFemaleHippocampusHumansLongitudinal StudiesMagnetic Resonance ImagingMaleNeuroimagingBiomarkersAlzheimer's diseaseDisease progressionHippocampus areaInterscan intervalLongitudinal analysisT1-weighted MRI

Identifiers

PMID34450261
PMCPMC8604562
OpenAlexW3196105426

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.