Whole Brain Connectome Mapping with Synchrotron X-rays

Yeukuang Hwu^1,2,3,4*

¹Institute of Physics, Academia Sinica, Taipei, Taiwan
²Brain Research Center, National Tsing Hua University, Hsinchu, Taiwan
³Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan
⁴Department of Engineering Science, National Cheng Kung University, Tainan, Taiwan

* Presenter:Yeukuang Hwu, email:phhwu@sinica.edu.tw

The complexity the complete neural networks in an animal brain is beyond the current technology to describe and analyze. Comprehensive mapping of neural network in a brain down to the connections of all the building blocks, the neurons, is therefore a formidable but very exciting challenge. Could x-ray techniques be the tool of choice to challenge the animal brain circuitry mapping? Is the overall performance adequate, however?
An effective strategy based on recent advances of x-ray tomography put itself into this competitive race. The approach reaches three critical objectives: (1) three-dimensional (3D) imaging with high and isotropic spatial resolution; (2) fast image taking and processing, as required for comprehensive whole-brain mapping within a reasonable time, and (3) multi-scale resolution, to zoom into specific regions of interest. The current performance is orders-of-magnitude faster than other 3D imaging techniques based on visible light microscopy while with sub-cellular resolution far superior than the medical imaging techniques. This strategy is extensively tested in the last few years by mapping large populations of metal-labeled neurons and their connections in two animal models, Drosophila and mouse.
These positive results instigated two additional directions for further improved. First, an even better spatial resolution and higher probe depth, both are relevant to the high brightness synchrotron radiation and the new nanofabrication facilities, can drastically enrich the content of the resulting database. Second, an ongoing project also aims to improve the heavy metal staining efficiency and specificity can improve the throughput of the whole brain imaging and achieving specific labeling simultaneously. The newly initiated SYNAPSE (Synchrotron for Neuroscience – an Asia Pacific Strategic Enterprise) consortium with 6 synchrotron and 4 supercomputing facilities, provide the necessary data acquisition and processing power and guarantee that a human brain can be mapped within 4 years.

Keywords: x-ray imaging, synchrotron radiation, brain imaging, tomography