IT之家 July 11th report, Professor Bi Guoqiang and Professor Liu Beiming from the University of Science and Technology of China, in collaboration with the team from the Hefei Comprehensive National Science Center Artificial Intelligence Research Institute and the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, have developed a breakthrough technology for whole-body sub-cellular resolution three-dimensional imaging of small animals, which is the fastest globally. This technology has achieved the first high-definition mapping of the detailed three-dimensional atlas of the mouse's entire neural network.
The related achievements were published on the international academic journal "Cell" on July 10th, Beijing Time (IT Home provides DOI: 10.1016/j.cell.2025.06.011), providing a new tool for understanding the peripheral nerve regulation network and disease mechanisms.
The peripheral nervous system, as the body's "Internet of Things," carries out bidirectional communication and regulation between the brain and all organs: on one hand, it transmits motor commands and regulates vital functions such as respiration and heartbeat; on the other hand, it returns sensory signals such as pain and temperature perception to the central nervous system for processing in real time, thus coordinating the activities of various tissues and organs. Mapping the detailed connection map of the entire body's peripheral nervous system is key to deeply understanding its complex functional mechanisms and related disease mechanisms.
For a long time, scientists' understanding of the overall architecture of the peripheral nervous system mainly relied on anatomical studies at the millimeter scale. Although advances in three-dimensional optical microscopy over the past decade have promoted the analysis of mesoscopic neural maps of the whole brain at the micrometer scale, research on the entire body's peripheral nervous system still faces technical bottlenecks. Existing cutting-edge imaging technologies struggle to simultaneously achieve high resolution and high imaging speed. Even with whole-body sample clearing, it remains difficult to resolve the complex long-range pathways of the peripheral nervous system at subcellular resolution across the entire mouse body.
The research team previously developed a novel synchronized scanning technology (VISoR), which combines large-volume biological sample thick sections and clearing for three-dimensional microscopic imaging. VISoR has the advantages of high speed, high resolution, and scalability, capable of completing sub-micron resolution imaging of the entire mouse brain within 1.5 hours, and further optimized to achieve the first micrometer-scale three-dimensional imaging of the monkey's entire brain and single-neuron fiber tracking.
However, this whole-brain imaging strategy of first sectioning and then clearing is not suitable for whole-body mouse samples. Unlike the relatively dense and homogeneous brain, the mouse's entire body has high heterogeneity, containing diverse tissue types and irregular structures, and during the sectioning process, the tissue tends to disperse and be lost, making it difficult to reconstruct completely.
To address this technical challenge, the team proposed a "sample in situ sectioning + section face three-dimensional imaging" strategy, and developed an integrated blockface-VISoR imaging system with a precision vibration sectioning device, as well as a complementary whole-body mouse clearing and hydrogel embedding sample preparation process called ARCHmap. The core of this technological process lies in: only the surface of the sample block about 600 micrometers deep is imaged three-dimensionally each time, then the 400 micrometers thick sample that has been imaged is automatically cut off, and this process is repeated until the entire sample is imaged. Subsequently, an automated stitching algorithm is used to perform three-dimensional seamless stitching reconstruction of the overlapping area of about 200 micrometers between adjacent slices. Since the scanning depth per scan is only hundreds of micrometers, the light scattering effect after tissue clearing is weak, so high-resolution imaging can be achieved. Based on this strategy, researchers established an optimized technical process, completing whole-body uniform sub-cellular resolution three-dimensional imaging of adult mice within 40 hours, obtaining approximately 70 TB of raw image data per channel. So far, data from dozens of mice have been collected, with a total volume exceeding 4 PB.
Due to the advantage of high fluorescence preservation in the sample preparation method, the ARCHmap-blockface-VISoR technology is compatible with fluorescent proteins commonly used in neuroscience, such as transgenic and neurotropic virus carrying fluorescent proteins, as well as immunofluorescence labeling methods. Combining these labels and imaging techniques, researchers successfully resolved the fine structure and single-fiber projection paths of different types of peripheral nerves in the mouse body, revealing for the first time the cross-segment projection characteristics of individual spinal neurons, clarifying the organ-specific vascular distribution pattern of the entire sympathetic nervous system, and analyzing the overall projection framework and complex projection paths of the vagus nerve.
Researchers stated that this groundbreaking technology not only helps establish a new paradigm for studying the connection map of the peripheral nervous system and resolving fundamental issues of neural regulatory structures, but also has important application prospects in developmental biology, systematic anatomy, and biomedical fields. In addition, there is still room for improvement and optimization of this technology. The next step will be to use dual or multi-camera imaging to simultaneously collect multi-channel images, improve data collection efficiency, and explore its application in larger-scale biological sample imaging areas.
Original: https://www.toutiao.com/article/7525654663086785050/
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