Introduction

The BMCR is a resource that provides access to anterograde and retrograde neuronal tracer data, currently restricted to injections into the prefrontal cortex of a marmoset brain. We are currently extending the resources with ISH gene expression image data from the Marmoset Gene Atlas (https://gene-atlas.brainminds.jp/), and integrating data from anterograde tracer injections covering the entire marmoset cortex. It comprises post-processed data and tools for exploring and reviewing the data, and for integration with other marmoset brain image databases and cross-species comparisons. We visualize data of different individuals in a common reference space at an unprecedented high resolution. Major features are:

• Image data of anterograde and retrograde neuronal tracers.
• The BMCR-Explorer for reviewing the data in high resolution
• dMRI tractography data that is associated with anterograde injection sites.
• Transformation fields to map between other marmoset brain image databases and atlas (Brain/MINDS Marmoset Reference Atlas, Marmoset Brain Mapping, Marmoset Brain Connectivity Atlas).
• Transformation fields to the human MNI space
• Flatmap stacks of neural tracer data (Including the all neccesary data to map other image data to flatmap stacks).
• Nora-StackApp for reviewing the data
• A left-right symmetric population-average brain image template based on serial two-photon tomography along with a left-right symmetric population-average HARDI, Nissl, and backlight image.
• We integrated retrograde neural tracer data from the Marmoset Brain Connectivity Atlas project.

Coming next

• ISH image data in nifti format.
• High resolution data from anterograde tracer injections covering the entire corext.

News

• 2024/10: Integrated image data from 260 Genes of adult marmosets from the Marmoset Gene Atlas (https://gene-atlas.brainminds.jp/) into the BMCR-Explorer
• 2024/9: BMCR-Explorer: Anterograde tracer segmentations have been updated (better coverage at brain boundaries)

Table of Contents

• BMCR Explorer (High resolution section viewer)
• Nora-StackApp and Data Download
• License
• BMCR-Explorer Tutorial
• Nora Tutorial
• Mapping between brain image spaces (Marmoset, Flatmastack, Human MNI)

Major Publications

These are our related publications. Please note that the data also incooperates data from other sources as well. Please carefully read the license files or hints in the BMCR-Explorer.

STPT tracer data integration and data acquision

• Serial Two-Photon Tomography Imaging of the whole marmoset brain for neuroanatomical analyses
  • A. Watakabe, T, Tani, H. Abe, H. Skibbe, N. Ichinohe, T. Yamamori
  • In bioRxiv, 2024

• Local and long-distance organization of prefrontal cortex circuits in the marmoset brain
  • A. Watakabe, H. Skibbe, K. Nakae, H. Abe, N. Ichinohe, M. F. Rachmadi, J. Wang, M. Takaji, H. Mizukami, A. Woodward, R. Gong, J. Hata, D. C. Van Essen, H. Okano, S. Ishii, T. Yamamori
  • In Neuron, 2023

• The Brain/MINDS Marmoset Connectivity Resource: An open-access platform for cellular-level tracing and tractography in the primate brain
  • H. Skibbe, M.F. Rachmadi, K. Nakae, C. E. Gutierrez, J. Hata, H. Tsukada, C. Poon, K. Doya, P. Majka, M. G. P. Rosa, M. Schlachter, H. Okano, T. Yamamori, S. Ishii, M. Reisert, A. Watakabe.
  • In PLoS Biology, 2023

ISH data integration

• An automated pipeline to create an atlas of in situ hybridization gene expression data in the adult marmoset brain
  • C. Poon, M.F. Rachmadi, M. Byra, M. Schlachter, B. Xu, T. Shimogori, H. Skibbe
  • In IEEE International Symposium on Biomedical Imaging Proceedings, 2023

Video: The video above illustrates some of the major parts of our image processing pipeline. It is a bit outdated. By that time, we completed the image processing for 41 cortical injections.

Brain/MINDS Marmoset Connectivity Resource

BMCR-Explorer

The BMCR-Explorer is publicly available online. You might find our introduction helpful. Or directly start by clicking on one of the example images below. The BMCR-Explorer works best with google-chrome, but should also work with the chromium, firefox and edge browsers. Safari might work. It also has touch support. It won't work with the Microsoft Internet Explorer :-(. We plan to release a downloadable offline version of the BMCR-Explorer in the future.

Click here or on one of the examples below to open the BMCR-Explorer

Nora-StackApp and Data Download and License

Nora-StackApp and data in the STPT reference image space

Video: Demonstration of the Nora-StackApp. The Nora-StackApp based on the nora medical imaging platform, which we extended with functions so that it interacts with BMCR-Explorer and flatmap stacks.

License

You can download the data from here. Further instructions for installing the Nora-stack app can be found here: Nora-Howto Our image data is published under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/deed.en).

The BMCR-Explorer and the downloadable dataset also includes data derived from four atlases that are work of other groups, which you might find helpful in reproducing and exploring our findings. Please carefully read the accompanying ‘Readme’ files, as some of the data is released under different licenses. If you find these data useful and plan to use it, then you must cite the original work, and accept their licenses. A summary of the atlas licenses is provided below:

• (1) Brain/MINDS 3D Marmoset Reference Brain Atlas 2019 (abbreviated as BMA)
  • web-link: https://dataportal.brainminds.jp/atlas-package-download-main-page/bma-2019-ex-vivo.
  • Reference:
    • Woodward, Alexander; Gong, Rui; Nakae, Ken; Hata, Junichi; Okano, Hideyuki; Ishii, Shin; Yamaguchi, Yoko : Brain/MINDS 3D Marmoset Reference Brain Atlas 2019 (DataID: 4520) https://doi.org/10.24475/bma.4520
  • License: Released under a Creative Commons Attribution 4.0 International License; check the webpage for details.
• (2) Data from the Marmoset Brain Connectivity Atlas (abbreviated as MBCA)
  • web-link: https://www.marmosetbrain.org/reference
  • References:
    • The Marmoset Brain in Stereotaxic Coordinates” by Paxinos, Watson, Petrides, Rosa and Tokuno (Academic Press, 2012)
    • Majka P., Bai S., Bakola S., Bednarek S., Chan J.C., Jermakow N., Passarelli L., Reser D.H., Theodoni P., Worthy K.H., Wang X-J., Wójcik D.K., Mitra P.P. & Rosa M.G.P. (2020). Open access resource for cellular-resolution analyses of corticocortical connectivity in the marmoset monkey. Nature Communications. http://doi.org/10.1038/s41467-020-14858-0
    • Majka P., Chaplin T.A., Yu, H.-H., Tolpygo A., Mitra P.P., Wójcik D.K., & Rosa M.G.P. (2016). Towards a comprehensive atlas of cortical connections in a primate brain: Mapping tracer injection studies of the common marmoset into a reference digital template. Journal of Comparative Neurology, 524(11), 2161–2181. http://doi.org/10.1002/cne.24023
  • Lincense: Released under a Creative Commons Attribution-ShareAlike 4.0 (CC-BY-SA) License; check the webpage for details.
• (3) Atlas data from the marmoset brain mapping project (version 2+3) (abbreviated as MBM)
• web-link: https://marmosetbrainmapping.org/atlas.html
  • References:
    • version 3: Liu C, et al. Marmoset Brain Mapping V3: Population multi-modal standard volumetric and surface-based templates. Neuroimage (2021) doi:10.1016/j.neuroimage.2020.117620.
    • version 2: Liu C, et al. A resource for detailed 3D mapping of white matter pathways in the marmoset brain. Nature Neuroscience (2020) doi:10.1038/s41593-019-0575-0.
  • Lincense: Released under a Creative Commons Attribution-NonCommercial-ShareAlike (CC BY-NC-SA 4.0) License; check the webpage for details.

Explorer Tutorials

Adjusting sizes

Basic controls

Mouse controls:

• Explained in Tutorial 00
  • Mouse wheel to zoom in or out, hold the “shift” key to fast zoom. hold the “ctr” key to inverse zooming direction

Keyboard controls:

Explained in Tutorial 00

• “a” and “d” : previous or next slice
• “w” and “s” : previous or next slice (fast)
• “space” : switching focus between left and right hemisphere

Explained in Tutorial ????

• “q” and “e” : select an image for the top layer, or the layer beneath the top layer, respectively
• “c” show the focus center
• “1” : hide or show the background image
• “2”,“3” : hide or show the image/annotation in the layer beneath the top layer (Background)
• “4”,“5” : hide or show the image/annotation in the top layer (Overlay)
• “6”,“7” : hide or show atlas information

Opening data and using the flatmap navigation

Acknowledgements

Voice has been generated using TTS (default parameters). https://github.com/mozilla/TTS

Nora-StackApp

The Nora-StackApp is based on the Nora medical imaging platform. Therefore, you might find the First Steps tutorial useful, too.

Basic keyboard and mouse controls:

Explained in Tutorial 00

• Keep the left mouse button pressed while moving the cursor to navigate withing slices
• Keep the right mouse button pressed while moving the cursor to shift a section
• Use the mouse wheel to switch slices
• Use the mouse wheel while keeping the control key pressed to zoom

You can also use the quick navigation menu as shown below:

Installation

Download a copy from the RIKEN CBS data portal. Select the NORA-StackApp folder as shown in the image below. To download the StackApp, click on the symbol in the upper right corner. It will open the download window (you might need to allow pop-up windows for the repository site). Below a screenshot of the download window: Please download the version for your OS (linux,mac or win). We have tested it on Ubuntu Linux, Windows 11 and an M1 Mac. Below a screenshot that illustrates how to run it from a Mac. Windows and Linux work in a similar way. You won't need to install the app, just unzip the folder. In the example below, we used the Desktop as destination. In a sub-folder of the unzipped folder, you will find the “Noraview” application (on Windows Noraview.exe). Starting it should bring up the main interface as shown below: The work-spaces menu provides several pre-defined work-spaces for marmosets.

Download Tracer Data

When you download the Nora-StackApp, you already have the atlases and the template images that are used for the work-spaces. But you might want to download tracer data image stacks and additional atlases from the RIKEN CBS data repository:

• Anterograde tracer data: “Volumetric_anterograde_tracer_data”
• Retrograde tracer from the Marmoset Brain Connectivity Project
• Atlases: Use the Nora-optimized versions under “STPT_reference_image_space” → “Nora-StackApp_versions”

Marmoset Workspaces

The Nora-StackApp shows multiple 3D image stacks in a grid of views. Each view can show a section of an image. A view shows one main image (e.g. a background image) and can have multiple “overlays”. An overlay can be another image, such as a tracer signal, or an atlas. The example below shows the default marmoset workspace with two views, each showing a different slicing. It also shows the atlas tool. You can increase or decrease the number of views. Having more views can be helpful to show two different images side-by-side. Reducing the number of views gives a view more space on the screen. The image below shows the default workspace, that shows our average template as background image. We have selected a nifti file with an anterograde tracer signal from our hard disk, and use the drag-and-drop feature of Nora to drop it into the first view as a new overlay. We then took the hand button of the tracer overlay and dropped it into the second view as well. Open the BMCA-Explorer, and use the brain-symbol shown below, and drag and drop it into the explorer to set the current Explorer position to the same position as in Nor The video below shows a demonstration, including interaction the with BMCA-Explorer:

Flatmap Stack and Human Brain Space Mapping

The BMCR dataset includes the STPT template images (with a population average STPT background image, a population average Nissl image, a population average backlit image and a population average HARDI. It further incooperates measurements derived from the population average HARDI. It also includes the ANTs warping field that maps data from our STPT template space to a flatmap-stack, and ANTs warping fields to map between other marmoset brain atlases (MARMOSET BRAIN CONNECTIVITY ATLAS, MARMOSET BRAIN MAPPING version 2 and 3, Brain/MINDS Marmoset Reference Atlas v1.1.0). It also includes the warping field between the STPT image space and the human MNI space.

Video: Demonstration of the warping field mapping from the STPT template image space to a human brain

Howto Flatmap-stack

Some code examples showing how to use the ANTs image registration toolkit to map marmoset brain images to a flatmap stack can be found here: https://github.com/BrainImageAnalysis/flatmap_stack/wiki.

Video: Demonstration of the warping field mapping from the STPT template image space to the 3D flatmap stack