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DeepAD: An automated and interpretable machine learning pipeline for image analyses of biomarkers in Alzheimer's disease

Research Project

Project/Area Number 22K15658
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Poon CharissaTingAmanda  国立研究開発法人理化学研究所, 脳神経科学研究センター, 基礎科学特別研究員 (40933130)

Project Period (FY) 2022-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2025: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsAlzheimer's disease / image registration / deep learning / segmentation / alzheimer's disease / glial cells / plaques / amyloid / image processing / microscopy / 画像情報処理・画像認識 / 分子・細胞・神経生物学 / 認知症疾患 / グリア細胞 / コンピュータビジョン
Outline of Research at the Start

Our goal is to create an automated tool to conduct image analyses common in Alzheimer's disease research, specifically: quantification of pathological Aβ plaques and glial cells. Automating analyses will reduce human error and bias, thereby improving the reproducibility of Alzheimer's disease research. The tool will be developed in collaboration with neuroscientists to ensure that it is easily understood and useful.

Outline of Annual Research Achievements

The goal is to create an interpretable automated image processing pipeline for microscopy images used in Alzheimer's disease research. Due to difficulty in obtaining transgenic animal data, we have been focusing on open datasets, specifically the Seattle Alzheimer's Disease Brain Cell Atlas, which consists of images of human brain tissue. Images of several biomarkers from several brain regions are available for each subject, but the lack of image alignment makes inter-subject comparison difficult. Our current pipeline employs a multi-stage image registration framework, where the first Rigid transformation is calculated using landmarks, which can be refined using deep learning methods. Development has been focused on tissue from the superior temporal and medial temporal brain regions.

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

Due to the delay in obtaining microscopy images of transgenic animal data, we have been developing the pipeline using open datasets of images obtained from human AD patients. However, the complexity of the human brain and the limited amount of tissue reflected in each image makes image alignment difficult to achieve. Furthermore, brain sections were likely cut at different angles, which further complicates alignment of brain sections from different individuals.
We are currently focusing on tissue from the superior temporal and medial temporal cortices as these are the most easily visually distinguishable among all the brain regions available in the dataset.

Strategy for Future Research Activity

Due to continued uncertainty in availability of animal datasets, we plan to proceed development based on the open Seattle Alzheimer's Disease Brain Cell atlas dataset.
The availability of quantitative data in the dataset, such as percentage of the brain occupied by glial biomarkers in different brain regions, is helpful for the validation of the segmentation component of the image processing pipeline.
An ongoing challenge is development and validation of the image registration component of the pipeline, as cropped human brain regions are more difficult to align than whole-brain sections from rodents, from which the original proposal was based on.
Furthermore, the resolution of images in the dataset may not be high enough to see detailed cell structure. As such, the characterization of cell morphology component in the pipeline may be limited. As a first step, we plan to attempt to represent cell shapes using simpler geometric shapes.

Report

(3 results)
  • 2024 Research-status Report
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (13 results)

All 2024 2023 2022

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Meta-learning for segmentation of in situ hybridization gene expression images2024

    • Author(s)
      Poon Charissa, Byra Michal, Shimogori Tomomi, Skibbe Henrik
    • Journal Title

      Medical Imaging with Deep Learning

      Volume: 1 Pages: 1-3

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Brain/MINDS Marmoset Connectivity Resource: An open-access platform for cellular-level tracing and tractography in the primate brain2023

    • Author(s)
      Skibbe Henrik、Rachmadi Muhammad Febrian、Nakae Ken、Gutierrez Carlos Enrique、Hata Junichi、Tsukada Hiromichi、Poon Charissa、Schlachter Matthias、Doya Kenji、Majka Piotr、Rosa Marcello G. P.、Okano Hideyuki、Yamamori Tetsuo、Ishii Shin、Reisert Marco、Watakabe Akiya
    • Journal Title

      PLOS Biology

      Volume: 21 Pages: 1-37

    • DOI

      10.1371/journal.pbio.3002158

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Improving Segmentation of Objects with Varying Sizes in Biomedical Images using Instance-wise and Center-of-Instance Segmentation Loss Function2023

    • Author(s)
      Rachmadi, Muhammad Febrian; Poon, Charissa; Skibbe, Henrik
    • Journal Title

      Proceedings of Machine Learning Research

      Volume: nnn Pages: 1,15

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An automated pipeline to create an atlas of in situ hybridization gene expression data in the adult marmoset brain2023

    • Author(s)
      Poon, Charissa; Rachmadi, Muhammad Febrian; Byra, Michal; Schlachter, Matthias; Xu, Binbin; Shimogori, Tomomi; Skibbe, Henrik
    • Journal Title

      International Symposium on Biomedical Imaging

      Volume: n/a Pages: 1,15

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] A 3D gene expression atlas of the adult marmoset brain2024

    • Author(s)
      Charissa Poon, Michal Byra, Muhammad Febrian Rachmadi, Matthias Schlachter, Meghane Decroocq, Binbin Xu, Ben Fulcher, Tomomi Shimogori, Henrik Skibbe
    • Organizer
      NEURO2024
    • Related Report
      2024 Research-status Report
    • Int'l Joint Research
  • [Presentation] A 3D gene expression atlas of the adult marmoset brain2024

    • Author(s)
      Poon Charissa, Byra Michal, Rachmadi Muhammad Febrian, Xu Binbin, Decroocq Meghane, Shimogori Tomomi, Skibbe Henrik
    • Organizer
      RIKEN Life Science Retreat
    • Related Report
      2023 Research-status Report
  • [Presentation] Meta-learning for segmention of in situ hybriization gene expression images2024

    • Author(s)
      Poon Charissa, Byra Michal, Shimogori Tomomi, Skibbe Henrik
    • Organizer
      Medical Imaging with Deep Learning
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] A 3D gene expression atlas of the adult marmoset brain2023

    • Author(s)
      Poon Charissa, Byra Michal, Rachmadi Muhammad Febrian, Xu Binbin, Decroocq Meghane, Shimogori Tomomi, Skibbe Henrik
    • Organizer
      RIKEN Center for Brain Science Retreat
    • Related Report
      2023 Research-status Report
  • [Presentation] An automated pipeline to create a gene expression atlas in the marmoset brain2023

    • Author(s)
      Poon Charissa, Byra Michal, Rachmadi Muhammad Febrian, Xu Binbin, Decroocq Meghane, Shimogori Tomomi, Skibbe Henrik
    • Organizer
      Japan Neuroscience Conference
    • Related Report
      2023 Research-status Report
  • [Presentation] An automated pipeline to create an atlas of in situ hybridization gene expression data in the adult marmoset brain2023

    • Author(s)
      Poon, Charissa; Rachmadi, Muhammad Febrian; Byra, Michal; Schlachter Matthias; Xu, Binbin; Shimogori, Tomomi; Skibbe, Henrik
    • Organizer
      International Symposium on Biomedical Imaging
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Semi-supervised semantic segmentation of in situ hybridization gene expression in the marmoset brain2022

    • Author(s)
      Poon, Charissa; Rachmadi, Muhammad Febrian; Byra, Michal; Shimogori, Tomomi; Skibbe, Henrik
    • Organizer
      Society for Neuroscience 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Semi-supervised semantic segmentation of in situ hybridization gene expression in the marmoset brain2022

    • Author(s)
      Poon, Charissa; Rachmadi, Muhammad Febrian; Byra, Michal; Shimogori, Tomomi; Skibbe, Henrik
    • Organizer
      The 45th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Semi-supervised semantic segmentation of in situ hybridization gene expression in the marmoset brain2022

    • Author(s)
      Poon, Charissa; Rachmadi, Muhammad Febrian; Byra, Michal; Shimogori, Tomomi; Skibbe, Henrik
    • Organizer
      International Symposium on Artificial Intelligence and Brain Science
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2025-12-26  

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