BEIJING, July 3 (Xinhua) -- Imagine tens of millions of table tennis balls spinning, bouncing, and even colliding with each other in a gigantic gymnasium. It is almost impossible to track every movement with human eyes.

A similar challenge had once shrouded the imaging of large-scale intercellular behaviors, but Chinese scientist Wu Jiamin and his colleagues, under the leadership of Prof. Dai Qionghai, addressed the problem by devising a series of computational mesoscale fluorescence microscopes.

In a laboratory at Tsinghua University, there lies the one-and-only microscope in the world that can realize 3D imaging of brain-wide subcellular dynamics in mice.

In April 2021, scientists employed the device to achieve the first intravital imaging of 3D subcellular dynamics at a millisecond scale in awake, behaving mice for more than six hours.

Wu, 30, one of its developers, is an assistant professor with the Department of Automation at Tsinghua University and has recently participated in developing mesoscale fluorescence microscopy through computational imaging methods.

These devices have enabled scientists to study large-scale intercellular behaviors in mammals across different physiological or pathological states, and relevant results have been published in journals including Nature and Cell.

"In the past, most of the life sciences research was constrained within vitro observation, and intravital imaging often faced enormous challenges such as tissue heterogeneity, scattering, phototoxicity, and 3D motions induced by respirations," said Wu.

"In brain science, for example, the brain is capable of making cognitive decisions while a single neuron in the brain does not have that function. How do neurons interact with each other? Why is this function of group behaviors possible?"

"We have known a lot about the structure of individual neurons. However, if we are not able to observe the large-scale intercellular behaviors, we can't study the emerging functions of neural networks with millions of neurons from a systematic perspective," Wu added.

He also noted that intravital imaging is subject to various interference, such as the vibration generated by animal respirations, which pose considerable challenges for high-speed 3D imaging.

Traditional optical instruments are designed for the human eyes, but Wu used information science technology to design "eyes" for the digital sensors in microscopy. He drew inspiration from the fine vibration structures of the compound eyes in insects, and broke complex imaging problems into a series of parallel small problems, changing the concept of traditional optical design.

The digital adaptive optics technology proposed by Wu et al. can record the information of every light ray with unprecedented accuracy and then reorganize and control their propagation in the digital world.

The technology overcomes the long-standing challenge of optical aberration in the physical world to recover high spatial resolution in complicated dynamic environments, thus realizing high-resolution high-speed 3D imaging in vivo across a wide field of view.

Researchers from Tsinghua University employed this instrument to realize brain-wide 3D neural imaging in awake-behaving mice at subcellular resolution and the imaging of subcellular dynamics of migrasomes during tumor metastasis in mammals, both of which are unprecedented globally.

Wu noted that the technology enables clinicians to judge whether the tumor is removed clearly and rapidly in real-time, and can also help scientists spot the process of wide-range tumor metastasis and study its mechanism.

Dai, an academician of the Chinese Academy of Engineering, said that Wu's work opens the door to understanding complex life activities under different physiological and pathological conditions from a systematic perspective, and is expected to reveal new mechanisms of neural circuits, tumor metastasis, and immune responses.

Wu and his colleagues have now been working on the development of next-generation computational mesoscopic and corresponding data analysis platforms, with an aim to capture and understand more phenomena in a wider, clearer, and faster manner, exploiting a new paradigm for high-throughput biological discoveries.

In the meantime, the research team has applied digital adaptive optics technology in other areas, including ground-based telescopes, mobile phone imaging, and automatic driving 3D perception.

Wu said that the emergence of information science has brought considerable changes to optics, and it is necessary to explore new fields in an interdisciplinary era constantly.

"I have been driven by curiosity in the research work, expecting to do something unique," Wu added.