Highest-resolution map of the entire human brain created

September 16, 2016

Allen Human Brain Reference Atlas image (credit: Allen Institute for Brain Science)

The Allen Institute for Brain Science has published the highest-resolution atlas of the human brain to date in a stand-alone issue of the Journal of Comparative Neurology. This digital human brain atlas allows researchers to investigate the structural basis of human brain function and is freely available as part of the suite of Allen Brain Atlas tools at brain-map.org.

“To understand the human brain, we need to have a detailed description of its underlying structure,” says Ed Lein, Ph.D., Investigator at the Allen Institute for Brain Science. “Human brain atlases have long lagged behind atlases of the brain of worms, flies or mice, both in terms of spatial resolution and in terms of completeness due to technical limitations related to the enormous size and complexity of the human brain. This large-scale focused effort aimed to create a large resource combining different data types at high resolution, and use these data to generate a comprehensive mapping of brain regions.”

Combining neuroimaging with cellular resolution histological analysis and expert structural mapping, “This is the most structurally complete atlas to date and we hope it will serve as a new reference standard for the human brain across different disciplines,” says Lein.

Cellular microscopic resolution

To create this modern atlas, the team at the Allen Institute partnered with Bruce Fischl, Ph.D. at Massachusetts General Hospital to perform magnetic resonance and diffusion tensor imaging on an intact brain before it was cut into slabs and serially sectioned to allow histological staining of individual sections. This imaging on the same brain created opportunities for linking fine molecular and cellular studies of the brain in health and disease with non-invasive neuroimaging studies.

The Allen Human Brain Reference Atlas digitized the histological data at true cellular microscopic resolution, creating a complete ontology of brain regions, and delineating all brain regions on a series of cross-sections through the brain. To image these sections, the Allen Institute team had to develop a new tile-based scanner that could image tissue sections the size of a complete human brain hemisphere at the resolution of 1 micrometer per pixel.

The Allen Human Brain Reference Atlas is an integrated, freely accessible online resource that allows users to navigate the brain and travel from the macroscopic scale of full brain sections to the level of individual neurons.

The Allen Human Brain Reference is “the only brain atlas to date to combine the rigor of a peer-reviewed scientific research paper with a presentation as a book format that includes the full set of annotated plates, open-access online availability of the resource with the ability to navigate and explore the details of any given area, and have programmatic access to the underlying data,” said Patrick Hof, M.D., Editor-in-Chief of the Journal of Comparative Neurology and a participant in the project.


Abstract of Comprehensive cellular-resolution atlas of the adult human brain

Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.