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Hierarchical X-ray imaging of the entire human brain

Research Project
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01.04.2019
 - 31.03.2023

The human brain with a weight of 1.3 kg contains around 1,000,000,000,000 cells. Current protocols for tissue imaging with cellular resolution involve optical and electron microscopies. Here, three-dimensional imaging requires serial sectioning due to the limited penetration depth. Sectioning, however, is destructive and artifact prone, with insufficient spatial resolution (perpendicular to the cuts) for visualizing cells. In the last decade, hard X-ray tomography has created virtual histology for imaging biological tissues with isotropic voxels at the micrometer scale and below. The question now arises: what is the highest achievable resolution for an atlas of the entire human brain? Currently, the best atlas is based on histological sectioning with 20 µm-wide voxels. Recent studies using synchrotron radiation-based hard X rays have imaged a full mouse brain with 0.8 µm pixel size, but the volume of a human brain is 3,000 times larger.The goal of this project is to generate an atlas of the entire human brain with 1 µm resolution. Hierarchical synchrotron radiation-based X-ray imaging will be performed at the beamline BM18 (European Synchrotron Radiation Facility - ESRF, Grenoble, France), which is under construction and will be unique with respect to beam size and transversal coherence. Here, full-field tomography of the entire human brain with voxel sizes of 20 µm and stitched local tomography acquisitions can be combined. The high-resolution imaging of the at least 12 cm-wide human brain poses several challenges, including sample preparation to withstand extreme radiation dose, acquisition protocols to keep the beamtime within limits, and data processing, which comprises slices of 100 GB and a total volume in the PB range.As the synchrotron radiation-based high-resolution X-ray measurements of the human brain can only be performed post mortem, we will make a correspondence from the ex vivo conditions back to the in vivo case in order to put this dataset into a more physiologically relevant context. Non-rigid registration of lower resolution magnetic resonance images of the human brain taken before extraction and throughout the fixation process allow for the quantification of the local deformations introduced during extraction, fixation, and embedding. In addition, the periodic high-resolution X-ray imaging of a mouse brain during the die-off process and subsequent tissue fixation and embedding will enable us to reasonably correct the brain's microanatomy. The synchrotron radiation-based X-ray imaging of the mouse brain with less than 1 µm voxel size will be carried out at the Biomedical beamline ID17 (ESRF, Grenoble, France), which is dedicated to biomedical imaging and radiation therapy.We want to make the big data yielding the microanatomy of the entire human brain freely available to the scientific community and for teaching purposes. This dataset will provide vital advances of relevance to a systems-level understanding of the human brain, maybe even close to physiological conditions. The hierarchical imaging procedure and the handling of the big imaging data is exemplary for further applications including comparatively studying entire healthy and diseased organs, industrially relevant engineering devices, and unique cultural heritage objects.

Funding

Hierarchical X-ray imaging of the entire human brain

SNF Schweizerischer Nationalfonds, 04.2019-03.2023 (48)
PI : Müller, Bert.
CI : Müller-Gerbl, Magdalena.

Members (3)

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Bert Müller

Principal Investigator
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Magdalena Müller-Gerbl

Co-Investigator
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Griffin Rodgers

Project Member