A scalable computational framework for large-scale imaging of neural circuits

Presented During:

Saturday, June 28, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre  
Room: M4 (Mezzanine Level)  

Poster No:

1788 

Submission Type:

Abstract Submission 

Authors:

Yael Balbastre1, Kabilar Gunalan2, Aaron Kanzer2, Elissa Bell3, Nathan Blanke3, Malte Casper4,5, Kaidong Chai3, Ting Gong3, Julia Lehman6, Chiara Maffei3, Emine Özen4,5, Wenze Li4,5, Gabriel Ramos Llorden3, Richard Schalek7, Jasmine Shao3, David Stansby1, Shruti Varade3, Jingjing Wu3, Susie Huang8, Peter Lee1, Jeff Lichtman7, Claire Walsh1, Hui Wang3, Zhuhao Wu9, Suzanne Haber10, Elizabeth Hillman4, Satra Ghosh2, Anastasia Yendiki3

Institutions:

1University College London, London, Greater London, 2Massachusetts Institute of Technology, Cambridge, MA, 3Massachusetts General Hospital, Charlestown, MA, 4Department of Biomedical Engineering, Columbia University in the City of New York, New York City, NY, 5Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University in the City of New York, New York City, NY, 6University of Rochester, Rochester, NY, 7Harvard University, Cambridge, MA, 8Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical, Boston, MA, 9Weill Cornell Medical College, New York City, NY, 10Rochester University, Rochester, NY

First Author:

Yael Balbastre  
University College London
London, Greater London

Co-Author(s):

Kabilar Gunalan  
Massachusetts Institute of Technology
Cambridge, MA
Aaron Kanzer  
Massachusetts Institute of Technology
Cambridge, MA
Elissa Bell  
Massachusetts General Hospital
Charlestown, MA
Nathan Blanke  
Massachusetts General Hospital
Charlestown, MA
Malte Casper  
Department of Biomedical Engineering, Columbia University in the City of New York|Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University in the City of New York
New York City, NY|New York City, NY
Kaidong Chai  
Massachusetts General Hospital
Charlestown, MA
Ting Gong  
Massachusetts General Hospital
Charlestown, MA
Julia Lehman  
University of Rochester
Rochester, NY
Chiara Maffei  
Massachusetts General Hospital
Charlestown, MA
Emine Özen  
Department of Biomedical Engineering, Columbia University in the City of New York|Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University in the City of New York
New York City, NY|New York City, NY
Wenze Li  
Department of Biomedical Engineering, Columbia University in the City of New York|Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University in the City of New York
New York City, NY|New York City, NY
Gabriel Ramos Llorden  
Massachusetts General Hospital
Charlestown, MA
Richard Schalek  
Harvard University
Cambridge, MA
Jasmine Shao  
Massachusetts General Hospital
Charlestown, MA
David Stansby  
University College London
London, Greater London
Shruti Varade  
Massachusetts General Hospital
Charlestown, MA
Jingjing Wu  
Massachusetts General Hospital
Charlestown, MA
Susie Huang  
Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical
Boston, MA
Peter Lee  
University College London
London, Greater London
Jeff Lichtman  
Harvard University
Cambridge, MA
Claire Walsh  
University College London
London, Greater London
Hui Wang  
Massachusetts General Hospital
Charlestown, MA
Zhuhao Wu  
Weill Cornell Medical College
New York City, NY
Suzanne Haber  
Rochester University
Rochester, NY
Elizabeth Hillman  
Department of Biomedical Engineering, Columbia University in the City of New York
New York City, NY
Satra Ghosh  
Massachusetts Institute of Technology
Cambridge, MA
Anastasia Yendiki  
Massachusetts General Hospital
Charlestown, MA

Introduction:

The NIH BRAIN Initiative Connectivity across Scales (CONNECTS) program was launched in 2023 to produce wiring diagrams of mammalian brains at unprecedented resolutions. Here we report on data standardization, integration, and visualization efforts in the center for Large-scale Imaging of Neural Circuits (LINC), a CONNECTS-funded consortium focused on the macaque and human brain. The LINC center will scale up novel optical and X-ray microscopy techniques to image a large brain volume (~12/360 cc in macaque/human) that contains cortico-subcortical projections targeted by neuromodulation for motor and psychiatric disorders. This volume will be imaged with: polarization-sensitive optical coherence tomography (PS-OCT; Liu, 2023) at 6μm; lightsheet microscopy (LSM; Voleti, 2019) at 0.6μm; and hierarchical phase-contrast tomography (HiP-CT; Walsh, 2021) at 0.87-17μm. Mesoscopic diffusion MRI (dMRI; Huang, 2021) in the same brains will provide the link to noninvasive neuroimaging.

Methods:

The computational ecosystem for data of this scale is still nascent. A human brain imaged at 1μm resolution would yield petascale data, prohibitive for the file formats and software packages used in human neuroimaging. In particular, such data (1) can be loaded in memory only in chunks; (2) must be compressed efficiently; (3) cannot be duplicated. Thus data must be stored on a cloud-based, distributed framework, in a format that allows efficient access to data chunks at different resolution levels suitable for different tasks. The electron-microscopy community has already adopted formats and tools to handle petascale data (Shapson-Coe, 2024). This includes Zarr, a chunked, compressed, distributed file format that allows efficient partial reads and writes, and OME-Zarr, an extension that supports multiscale data and spatial metadata (Moore, 2021). The Neuroglancer viewer supports OME-Zarr and operates purely client-side-data streams from source to client, bypassing the webserver, which is thus very lightweight. However, it lacks key features of desktop neuroimaging viewers (spatial transformations, image fusion, integrated annotation and visualization of common volume, surface, and streamline formats). Our approach for the LINC project is to bridge these worlds, combining the scalability of OME-Zarr and Neuroglancer with the usability of human neuroimaging tools.

Results:

For data storage, we have adopted the Distributed Archives for Neurophysiology Data Integration (DANDI; Rübel, 2022), a cloud-based platform that enforces the BIDS standard, supports OME-Zarr, and enables byte-range access via HTTP requests, so that data can be mounted and accessed by virtual file systems. As the Zarr specification does not handle general affine transforms, or other NIfTI-style metadata, we have drafted NIfTI-Zarr, an extension that preserves NIfTI header fields (github.com/neuroscales/nifti-zarr). We have developed a library for converting the native file formats of our data-generating sites to NIfTI-Zarr (Fig.1), while auto-populating BIDS metadata (github.com/lincbrain/linc-convert). Our cloud-based platform can open data in Neuroglancer for visualization or Webknossos (Boergens, 2017) for annotation (Fig.2). We are extending Neuroglancer with (1) support for visualizing tractography streamlines (github.com/lincbrain/neuroglancer) and (2) a library for easy setup of multi-modal Neuroglancer scenes that can import neuroimaging formats and transforms (github.com/neuroscales/ngtools).
Supporting Image: figure1_resize.png
Supporting Image: figure2_resize.png
 

Conclusions:

We have prototyped a scalable framework to bridge the whole-brain coverage of noninvasive neuroimaging and the single-axon resolution of microscopy. Future efforts will focus on interactive annotation of tractography streamlines. A key implication for the neuroimaging software stack is that files can no longer be assumed to live on the local filesystem. Developers must support abstract file systems so that code can operate seamlessly on local or remote files.

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

White Matter Anatomy, Fiber Pathways and Connectivity 1

Neuroinformatics and Data Sharing:

Workflows 2

Novel Imaging Acquisition Methods:

Diffusion MRI
Multi-Modal Imaging

Keywords:

Cross-Species Homologues
Data Organization
Open Data
Open-Source Software
Tractography
White Matter

1|2Indicates the priority used for review

Abstract Information

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Please indicate which methods were used in your research:

Optical Imaging
Diffusion MRI
Postmortem anatomy

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3.0T

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Free Surfer
Other, Please list  -   https://github.com/balbasty/nitorch

Provide references using APA citation style.

Boergens, K. M., Berning, M., Bocklisch, T., Bräunlein, D., Drawitsch, F., Frohnhofen, J., ... & Helmstaedter, M. (2017). webKnossos: efficient online 3D data annotation for connectomics. Nature methods, 14(7), 691-694.

Huang, S. Y., Witzel, T., Keil, B., Scholz, A., Davids, M., Dietz, P., ... & Rosen, B. R. (2021). Connectome 2.0: Developing the next-generation ultra-high gradient strength human MRI scanner for bridging studies of the micro-, meso-and macro-connectome. NeuroImage, 243, 118530.

Liu, C. J., Ammon, W., Jones, R. J., Nolan, J. C., Gong, D., Maffei, C., ... & Wang, H. (2023). Quantitative imaging of three-dimensional fiber orientation in the human brain via two illumination angles using polarization-sensitive optical coherence tomography. bioRxiv, 2023-10.

Moore, J., Allan, C., Besson, S., Burel, J. M., Diel, E., Gault, D., ... & Swedlow, J. R. (2021). OME-NGFF: a next-generation file format for expanding bioimaging data-access strategies. Nature methods, 18(12), 1496-1498.

Rübel, O., Tritt, A., Ly, R., Dichter, B. K., Ghosh, S., Niu, L., ... & Bouchard, K. E. (2022). The Neurodata Without Borders ecosystem for neurophysiological data science. Elife, 11, e78362.

Shapson-Coe, A., Januszewski, M., Berger, D. R., Pope, A., Wu, Y., Blakely, T., ... & Lichtman, J. W. (2024). A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution. Science, 384(6696), eadk4858.

Voleti, V., Patel, K. B., Li, W., Perez Campos, C., Bharadwaj, S., Yu, H., ... & Hillman, E. M. (2019). Real-time volumetric microscopy of in vivo dynamics and large-scale samples with SCAPE 2.0. Nature methods, 16(10), 1054-1062.

Walsh, C. L., Tafforeau, P., Wagner, W. L., Jafree, D. J., Bellier, A., Werlein, C., ... & Lee, P. D. (2021). Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography. Nature methods, 18(12), 1532-1541.

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