Imaging Methods and Techniques of Neuroscience
The brain is the most complex organ of the human body. Hundreds of billions of neurons, glial, microglia, and vascular tissue control emotions, sleep, cognitive mechanisms, and the occurrence and development of neurological diseases. Because imaging technology directly visualizes neurons or chemical information, from a single molecule to the entire brain level, thus, it has become an important tool for neuroscience and clinical research.
Imaging Methods and Techniques of Neuroscience
- Fluorescence imaging
Fluorescence imaging is a common method to track chemical changes in the nervous system, such as action potentials, calcium changes, or the release of neurotransmitters in vivo and in vitro. Fluorescence imaging is widely used in the study of biological processes at the molecular and cellular level due to its good temporal and spatial resolution, as well as high selectivity and sensitivity.
Table.1 Fluorescence imaging tools.
|Genetically encoded fluorescent biosensors||Non-genetically encoded fluorescent biosensors|
|Genetically encoded Ca2+ indicators (GECIs)||Ligand based fluorescent probes|
|Genetically encoded voltage indicators (GEVIs)||Quantum dots (QDs)|
|Cell-based neurotransmitter fluorescent engineered reporters (CNiFERs)||Fluorescent false neurotransmitters (FFNs)|
|Fluorescent molecular logic gates|
- Optical imaging
Optical methods such as confocal and two-photon microscopy have been widely used in brain imaging. Micro-optical slice tomography (MOST) system can reconstruct the 3D image of the whole brain and realize the micron-level whole mouse brain imaging. The schematic diagram is shown in Fig.1. One-photon optical microscopy is used for high-resolution molecular imaging of thick biological tissues, combined with two-photon microscopy can be further improved the imaging depth.
Fig.1 MOST imaging principle diagram. (Zhu, 2017)
- Functional Magnetic Resonance Imaging (FMRI)
- Blood oxygenation level dependent (BOLD)-FMRI
- Molecular FMRI
- Positron emission tomography (PET) imaging
- Mass spectrometry (MS) imaging
FMRI is a non-invasive neuroimaging technique that assesses the structure and function of the brain. A typical FMRI measures brain activity by detecting changes in oxygen content related to blood flow. FMRI can be used for long-term longitudinal studies of the same animal to study the interaction between neuronal activity and behavior, as well as the effects of acute and chronic drug treatments. It includes:
PET is a highly sensitive imaging technology of neural activity. This technology uses radiolabeled molecules (tracers) to metabolize and release positrons in vivo, detect positrons and map them out in space. PET is used to map cellular processes related to brain activity.
MS is an emerging analytical technique for studying the rich chemical information of samples in neuroscience. Analytes are directly ionized and then quantified by MS, such as proteins, peptides, neurotransmitters, and metabolites in nerve tissue. It provides a wealth of chemical information of the sample. Besides, different mass spectrometry ionization methods have been developed to detect different molecules, such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), secondary ion mass spectrometry (SIMS), desorption electrospray ionization mass spectrometry (DESI-MS), nanospray desorption electrospray ionization mass spectrometry (nano-DESI MS). These new technologies will advance the application of mass spectrometry imaging in neuroscience.
Fig.2 DESI-MS images of neurotransmitters in coronal rat brain tissue sections. (Ganesana, 2017)
Application of Imaging Technology in Neuroscience
Advances in imaging technology provide a variety of tools for assessing changes in brain neurons and cells. In fact, many recent advances in genetics are closely related to imaging methods, which can monitor the path of a specific probe inserted into a given neuron in real time. Each imaging technology has its own advantages and disadvantages, but all methods will benefit from multiplexing technology, which allows us to better understand the mechanisms of brain activity and neurological diseases.
- Atomic Force Microscopy (AFM) in Neuroscience
- Cholinergic System Imaging
- Deep-brain Imaging
- Diffusion Tensor Imaging (DTI)
- Digital Holographic Microscopy (DHM)
- Functional MRI (fMRI) Studies
- Nuclear Magnetic Resonance (NMR) Spectroscopy
- Imaging Studies Using Reporter-Gene Transgenic Rats
- Optical Monitoring of Exo- and Endocytosis
- Ultrastructural Analysis of Spine Plasticity
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- Zhu, X.; et al. Optical brain imaging: a powerful tool for neuroscience. Neuroscience bulletin. 2017, 33(1): 95-102.
- Ganesana, M.; et al. Analytical techniques in neuroscience: recent advances in imaging, separation, and electrochemical methods. Analytical chemistry. 2017, 89(1): 314-341.