1. Neuroscience

Automated hippocampal unfolding for morphometry and subfield segmentation with HippUnfold

  1. Jordan DeKraker  Is a corresponding author
  2. Roy AM Haast
  3. Mohamed D Yousif
  4. Bradley Karat
  5. Jonathan C Lau
  6. Stefan Köhler
  7. Ali R Khan  Is a corresponding author
  1. University of Western Ontario, Canada
  2. Aix-Marseille University, France
https://doi.org/10.7554/eLife.77945
Share this article
Cite this article
  1. Jordan DeKraker
  2. Roy AM Haast
  3. Mohamed D Yousif
  4. Bradley Karat
  5. Jonathan C Lau
  6. Stefan Köhler
  7. Ali R Khan
(2022)
Automated hippocampal unfolding for morphometry and subfield segmentation with HippUnfold
eLife 11:e77945.
https://doi.org/10.7554/eLife.77945
  2. Download BibTeX
  3. Download .RIS

Abstract

Like neocortical structures, the archicortical hippocampus differs in its folding patterns across individuals. Here, we present an automated and robust BIDS-App, HippUnfold, for defining and indexing individual-specific hippocampal folding in MRI, analogous to popular tools used in neocortical reconstruction. Such tailoring is critical for inter-individual alignment, with topology serving as the basis for homology. This topological framework enables qualitatively new analyses of morphological and laminar structure in the hippocampus or its subfields. It is critical for refining current neuroimaging analyses at a meso- as well as micro-scale. HippUnfold uses state-of-the-art deep learning combined with previously developed topological constraints to generate uniquely folded surfaces to fit a given subject's hippocampal conformation. It is designed to work with commonly employed sub-millimetric MRI acquisitions, with possible extension to microscopic resolution. In this paper we describe the power of HippUnfold in feature extraction, and highlight its unique value compared to several extant hippocampal subfield analysis methods.

Data availability

All code for the HippUnfold application has been made available at https://github.com/khanlab/hippunfold. Data and code to generate the Figures shown in this study have been made available at https://zenodo.org/record/6360647.

The following previously published data sets were used

Article and author information

Author details

  1. Jordan DeKraker

    University of Western Ontario, London, Canada
    For correspondence
    jordan.dekraker@mail.mcgill.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4093-0582

  2. Roy AM Haast

    Aix-Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Mohamed D Yousif

    University of Western Ontario, London, Canada
    Competing interests
    The authors declare that no competing interests exist.

  4. Bradley Karat

    University of Western Ontario, London, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6550-1418

  5. Jonathan C Lau

    University of Western Ontario, London, Canada
    Competing interests
    The authors declare that no competing interests exist.

  6. Stefan Köhler

    Brain and Mind Institute, University of Western Ontario, london, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1905-6453

  7. Ali R Khan

    University of Western Ontario, London, Canada
    For correspondence
    alik@robarts.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0760-8647

Funding

Canadian HIV Trials Network, Canadian Institutes of Health Research (366062)

  • Stefan Köhler
  • Ali R Khan

Canada Research Chairs (950-231964)

  • Ali R Khan

Natural Sciences and Engineering Research Council of Canada (6639)

  • Ali R Khan

Canada Foundation for Innovation (37427)

  • Ali R Khan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Birte U Forstmann, University of Amsterdam, Netherlands

Ethics

Human subjects: Informed consent and consent to publish were obtained by the original authors of the open source data examined here. Each of the three datasets included research ethics board approvals, as well as informed consent and, in the HCP-Aging dataset, assessment of the subjects' ability to provide consent. For the single epilepsy patient case examined here, research ethics board approval and informed consent were collected at the Western University (HSREB # 108952, Lawson: R-17-156).

Version history

  1. Preprint posted: December 5, 2021 (view preprint)
  2. Received: February 17, 2022
  3. Accepted: December 13, 2022
  4. Accepted Manuscript published: December 15, 2022 (version 1)
  5. Version of Record published: January 10, 2023 (version 2)

Copyright

© 2022, DeKraker et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,546
    views
  • 273
    downloads
  • 21
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jordan DeKraker
  2. Roy AM Haast
  3. Mohamed D Yousif
  4. Bradley Karat
  5. Jonathan C Lau
  6. Stefan Köhler
  7. Ali R Khan
(2022)
Automated hippocampal unfolding for morphometry and subfield segmentation with HippUnfold
eLife 11:e77945.
https://doi.org/10.7554/eLife.77945

Share this article

https://doi.org/10.7554/eLife.77945

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Neuroscience

    KIS counteracts PTBP2 and regulates alternative exon usage in neurons

    Marcos Moreno-Aguilera, Alba M Neher ... Carme Gallego
    Research Article Updated

    Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.

    1. Genetics and Genomics
    2. Neuroscience

    Genetic Chimerism: Marmosets contain multitudes

    Kenneth Chiou, Noah Snyder-Mackler
    Insight

    Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.

    1. Cell Biology
    2. Neuroscience

    Unraveling the link between Neuropathy Target Esterase NTE/SWS, lysosomal storage diseases, inflammation, abnormal fatty acid metabolism, and leaky brain barrier

    Mariana I Tsap, Andriy S Yatsenko ... Halyna R Shcherbata
    Research Article

    Mutations in Drosophila Swiss Cheese (SWS) gene or its vertebrate orthologue Neuropathy Target Esterase (NTE) lead to progressive neuronal degeneration in flies and humans. Despite its enzymatic function as a phospholipase is well-established, the molecular mechanism responsible for maintaining nervous system integrity remains unclear. In this study, we found that NTE/SWS is present in surface glia that forms the blood-brain-barrier (BBB) and that NTE/SWS is important to maintain its structure and permeability. Importantly, BBB glia-specific expression of Drosophila NTE/SWS or human NTE in the sws mutant background fully rescues surface glial organization and partially restores BBB integrity, suggesting a conserved function of NTE/SWS. Interestingly, sws mutant glia showed abnormal organization of plasma membrane domains and tight junction rafts accompanied by the accumulation of lipid droplets, lysosomes, and multilamellar bodies. Since the observed cellular phenotypes closely resemble the characteristics described in a group of metabolic disorders known as lysosomal storage diseases (LSDs), our data established a novel connection between NTE/SWS and these conditions. We found that mutants with defective BBB exhibit elevated levels of fatty acids, which are precursors of eicosanoids and are involved in the inflammatory response. Also, as a consequence of a permeable BBB, several innate immunity factors are upregulated in an age-dependent manner, while BBB glia-specific expression of NTE/SWS normalizes inflammatory response. Treatment with anti-inflammatory agents prevents the abnormal architecture of the BBB, suggesting that inflammation contributes to the maintenance of a healthy brain barrier. Considering the link between a malfunctioning BBB and various neurodegenerative diseases, gaining a deeper understanding of the molecular mechanisms causing inflammation due to a defective BBB could help to promote the use of anti-inflammatory therapies for age-related neurodegeneration.