Evidence map›Paper›PMID 34933123›Full record

ArticleNeuroImage2022

Deep learning for Alzheimer's disease: Mapping large-scale histological tau protein for neuroimaging biomarker validation.

Daniela Ushizima, Yuheng Chen, Maryana Alegro, Dulce Ovando, Rana Eser, WingHung Lee, Kinson Poon, Anubhav Shankar, Namrata Kantamneni, Shruti Satrawada and 4 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NeuroImage, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02350634 (A High Resolution Autopsy Study Evaluating the Relationship of 18F-AV-1451 PET Imaging and Tau Pathology), which is not on this map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
6.5field-weighted citation impact, top 4% 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.

NCT02350634 phase1completednot on this map

A High Resolution Autopsy Study Evaluating the Relationship of 18F-AV-1451 PET Imaging and Tau Pathology

TypeinterventionalSponsorAvid RadiopharmaceuticalsRan2016 to 2017Enrolled3ConditionsAlzheimer's DiseaseArmsFlortaucipir F18
3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Correlation between in vivoAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Three-dimensional histology reveals dissociable human hippocampal long-axis gradients of Alzheimer's pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Deep Learning-Based Diagnosis of Alzheimer's Disease.Journal of personalized medicine · 2022
    Review
  18. Artificial intelligence and Big Data in neurology.Arquivos de neuro-psiquiatria · 2022
    Article
  19. Article
  20. Review
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

14 authors at 3 institutions in 3 countries.

Daniela UshizimaBakar Institute for Computational Health Sciences, University of California San Francisco, CA, USA; Berkeley Institute for Data Science, University of California Berkeley, CA, USA; Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Yuheng ChenDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Maryana AlegroBakar Institute for Computational Health Sciences, University of California San Francisco, CA, USA; Berkeley Institute for Data Science, University of California Berkeley, CA, USA; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Dulce OvandoDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Rana EserDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
WingHung LeeDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Kinson PoonDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Anubhav ShankarDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Namrata KantamneniDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Shruti SatrawadaDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Edson Amaro JuniorUniversity of Sao Paulo Medical School, Sao Paulo, Brazil.
Helmut HeinsenUniversity of Sao Paulo Medical School, Sao Paulo, Brazil; Julius-Maximilians University Würzburg, Würzburg, Germany.
Duygu TosunDepartment of Radiology, University of California San Francisco, San Francisco, CA, USA; Veterans Affairs San Francisco, CA, USA.
Lea T GrinbergBakar Institute for Computational Health Sciences, University of California San Francisco, CA, USA; Department of Neurology, University of California San Francisco, San Francisco, CA, USA; University of Sao Paulo Medical School, Sao Paulo, Brazil; Department of Pathology, University of California San Francisco, San Francisco, CA, USA. Electronic address: lea.grinberg@ucsf.edu.
University of California, San Francisco · USUniversidade de São Paulo · BRUniversity of California, Berkeley · US

Funding

Project 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2016 to 2020
$10.8M
Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSPR01AG060477 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lea Tenenholz Grinberg, Thomas C Neylan · 2019 to 2026
$8.2M
Imaging brain iron and protein aggregation with MRI for assessing Alzheimer's disease pathology and progressionR01AG070826 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI GRINBERG, LEA TENENHOLZ, LIU, CHUNLEI · 2021 to 2025
$3.3M
Brainstem connectomes related to Alzheimer's diseaseRF1AG056573 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SHI, YONGGANG · 2018 to 2018
$2.5M
Neuropathological changes underlying clinical heterogeneity in Alzheimer diseaseK24AG053435 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ · 2016 to 2025
$1.8M
Uncovering how serotonergic signaling non-autonomously regulates protein homeostasisR01AG050653 · NIA · UNIVERSITY OF IOWA · PI PRAHLAD, VEENA · 2016 to 2020
$1.5M
NIA NIH HHS K24 AG053435NIA NIH HHS R01 AG050653NIA NIH HHS R01AG056573NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG070826NIA NIH HHS RF1 AG056573NINDS NIH HHS U54 NS100717
6 · The paper itself

Abstract

Abnormal tau inclusions are hallmarks of Alzheimer's disease and predictors of clinical decline. Several tau PET tracers are available for neurodegenerative disease research, opening avenues for molecular diagnosis in vivo. However, few have been approved for clinical use. Understanding the neurobiological basis of PET signal validation remains problematic because it requires a large-scale, voxel-to-voxel correlation between PET and (immuno) histological signals. Large dimensionality of whole human brains, tissue deformation impacting co-registration, and computing requirements to process terabytes of information preclude proper validation. We developed a computational pipeline to identify and segment particles of interest in billion-pixel digital pathology images to generate quantitative, 3D density maps. The proposed convolutional neural network for immunohistochemistry samples, IHCNet, is at the pipeline's core. We have successfully processed and immunostained over 500 slides from two whole human brains with three phospho-tau antibodies (AT100, AT8, and MC1), spanning several terabytes of images. Our artificial neural network estimated tau inclusion from brain images, which performs with ROC AUC of 0.87, 0.85, and 0.91 for AT100, AT8, and MC1, respectively. Introspection studies further assessed the ability of our trained model to learn tau-related features. We present an end-to-end pipeline to create terabytes-large 3D tau inclusion density maps co-registered to MRI as a means to facilitate validation of PET tracers.

Indexed as

Deep LearningAgedAged, 80 and overAlzheimer DiseaseBiomarkersDatasets as TopicEquipment DesignFemaleHumansImaging, Three-DimensionalMagnetic Resonance ImagingMaleNeuroimagingPhotomicrographytau ProteinsTomography, X-Ray ComputedBiomarkerstau ProteinsAlzheimer's diseaseBig dataConvolutional neural networksDeep learningDigital pathologyHistopathologyImagingMachine learning

Identifiers

PMID34933123
PMCPMC8983026
OpenAlexW4221056339

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.