Cholinergic System Imaging
Introduction of Cholinergic System
Acetylcholine is an important neurotransmitter that regulates brain neurons and glial activity. Significant loss of cholinergic cells was observed in the brains of patients with Alzheimer’s disease (AD) in the nucleus basalis of Meynert (NBM) and Parkinson’s disease (PD) patients after death. In addition, studies have shown that cholinergic nerve defects in Lewy body disease (LBD) may be more pronounced than AD. Recent neuroscience research has further confirmed the important role of cholinergic neurotransmission in cognitive function, especially attention and memory coding.
Cholinergic Receptor Imaging
Molecular imaging methods, such as positron emission tomography (PET) or single photon computed tomography (SPECT), can assess the cholinergic neurotransmission system of the living brain. Magnetic resonance imaging (MRI) plays a key role in the assessment of cholinergic basal forebrain (CBFB) containing NBM. By controlling the presence of important cognitive disease markers, such as proteinopathy or dopaminergic degeneration, multimodal imaging methods are of particular importance for studying the more specific relationship between cholinergic marker changes and cognition.
Studies have found that there is a significant correlation between reduced receptor binding in AD and PD and cognitive ability. Recently, spatial covariance studies using VAChT or AChE ligands have been used to explore the brain networks of cholinergic AD and LBD.
Fig.1 Acetylcholine nerve terminal presynaptic and postsynaptic molecular choline imaging target map. (Bohnen, 2018)
Applications of Cholinergic System Imaging
- MRI CBFB measurement research
- PET study PD cholinergic system changes
The MRI CBFB measurement study serves as a complement to molecular imaging techniques to assess cholinergic denervation control. Volume analysis of CBFB in high-resolution MRI scans can be used as a surrogate measurement of cholinergic degeneration in aging and disease in vivo, allowing the assessment of cholinergic degeneration in different CBFB subregions.
In the early stages of in vivo acetylcholine transport and acetylcholinesterase imaging studies in PD, it has consistently been shown that the presence of dementia in PD is associated with more severe and extensive cortical choline loss compared to PD without dementia. Fig.2 showed that PET imaging in PD patients has significant differences in brain absorption in different simulated regions of the cholinergic system.
Fig.2 Multiligand cholinergic PET study in a single PD subject. (Bohnen, 2018)
- Multimodal CBFB MRI volume measurement and PET imaging of glucose metabolism
Combining MRI-based CBFB volume measurement with additional imaging methods PET (such as glucose metabolism) for the assessment of cortical synaptic function, the results indicate that the effect of CBFB degeneration on cognitive impairment may be mediated by cortical neuronal dysfunction, cortical neuron dysfunction is the result of choline exhaustion in the target area of the denervated cortex.
Choline molecular imaging technology mainly focused on imaging the projection area to assess the integrity of cholinergic neurons in the primary cell group, increasing the camera resolution will allow direct visualization and quantification of cholinergic binding in the primary cell group. Choline molecular imaging can also assess striatal cholinergic internal medicine and brain cholinergic nerve endings. The molecular imaging assessment of the cholinergic system will help the future development of choline drugs for AD and PD.
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- Bohnen, N.I.; et al. Molecular imaging of the cholinergic system in Parkinson's disease. International review of neurobiology. 2018, 141: 211-250.