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. 2022 Dec 9;66(2):324–366. doi: 10.1007/s11426-022-1408-5

Structural and functional imaging of brains

Zhichao Liu 1,#, Ying Zhu 2,#, Liming Zhang 1,#, Weiping Jiang 3,#, Yawei Liu 4,#, Qiaowei Tang 2, Xiaoqing Cai 2, Jiang Li 2, Lihua Wang 2, Changlu Tao 7, Xianzhen Yin 8, Xiaowei Li 9, Shangguo Hou 10, Dawei Jiang 11, Kai Liu 5, Xin Zhou 3,✉, Hongjie Zhang 4,5,✉, Maili Liu 3,✉, Chunhai Fan 6,✉, Yang Tian 1,✉
PMCID: PMC9753096  PMID: 36536633

Abstract

Analyzing the complex structures and functions of brain is the key issue to understanding the physiological and pathological processes. Although neuronal morphology and local distribution of neurons/blood vessels in the brain have been known, the subcellular structures of cells remain challenging, especially in the live brain. In addition, the complicated brain functions involve numerous functional molecules, but the concentrations, distributions and interactions of these molecules in the brain are still poorly understood. In this review, frontier techniques available for multiscale structure imaging from organelles to the whole brain are first overviewed, including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), serial-section electron microscopy (ssEM), light microscopy (LM) and synchrotron-based X-ray microscopy (XRM). Specially, XRM for three-dimensional (3D) imaging of large-scale brain tissue with high resolution and fast imaging speed is highlighted. Additionally, the development of elegant methods for acquisition of brain functions from electrical/chemical signals in the brain is outlined. In particular, the new electrophysiology technologies for neural recordings at the single-neuron level and in the brain are also summarized. We also focus on the construction of electrochemical probes based on dual-recognition strategy and surface/interface chemistry for determination of chemical species in the brain with high selectivity and long-term stability, as well as electrochemophysiological microarray for simultaneously recording of electrochemical and electrophysiological signals in the brain. Moreover, the recent development of brain MRI probes with high contrast-to-noise ratio (CNR) and sensitivity based on hyperpolarized techniques and multi-nuclear chemistry is introduced. Furthermore, multiple optical probes and instruments, especially the optophysiological Raman probes and fiber Raman photometry, for imaging and biosensing in live brain are emphasized. Finally, a brief perspective on existing challenges and further research development is provided.

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Keywords: brain structure, brain function, brain chemistry, chemical signal, biosensing and bioimaging

Acknowledgements

This work was supported by the National Natural Science Foundation of China (22004037 for Liu Z; 22022410 and 82050005 for Zhu Y; 22022402 and 21974051 for Zhang L; 21635003 and 21811540027 for Tian Y; 22125701 and 21834007 for Liu K; 22020102003 for Zhang H; 91859206 and 21921004 for Zhou X), the Innovation Program of Shanghai Municipal Education Commission (201701070005E00020 for Tian Y), the Research Funds of Happiness Flower ECNU (2020JK2103 for Tian Y), the Shanghai Municipal Science and Technology Commission (19JC1410300 for Fan C), the Youth Innovation Promotion Association of CAS (2016236 for Zhu Y), and the National Key Research and Development Project of China (2018YFA0704000 for Zhou X).

Conflict of interest The authors declare no conflict of interest.

Footnotes

These authors contributed equally to this work.

Contributor Information

Xin Zhou, Email: xinzhou@wipm.ac.cn.

Hongjie Zhang, Email: hjzhang2019@mail.tsinghua.edu.cn.

Maili Liu, Email: ml.liu@wipm.ac.cn.

Chunhai Fan, Email: fanchunhai@sjtu.edu.cn.

Yang Tian, Email: ytian@chem.ecnu.edu.cn.

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