Applying a New Imaging Tool to Common Brain Disorders

Summary: A new imaging technique may provide researchers with better insights into neurological disorders.

Source: Yale.

A Yale-led team of researchers developed a new approach to scanning the brain for changes in synapses that are associated with common brain disorders. The technique may provide insights into the diagnosis and treatment of a broad range of disorders, including epilepsy and Alzheimer’s disease.

The study was published July 20 in Science Translational Medicine.

Certain changes in synapses — the junctions between nerve cells in the brain — have been linked with brain disorders. But researchers have only been able to evaluate synaptic changes during autopsies. For their study, the research team set out to develop a method for measuring the number of synapses, or synaptic density, in the living brain.

To quantify synapses throughout the brain, professor of radiology and biomedical imaging Richard Carson and his coauthors combined PET scanning technology with biochemistry. They developed a radioactive tracer that, when injected into the body, binds with a key protein that is present in all synapses across the brain. They observed the tracer through PET imaging and then applied mathematical tools to quantify synaptic density.

Image shows a brain.
Human synaptic density images derived from PET scans. The sequential images are coronal slices (from front to back of the brain), sagittal slices (from left to right), and transverse images (from bottom to top). NeuroscienceNews.com image is credited to Yale PET Center.

The researchers used the imaging technique in both baboons and humans. They confirmed that the new method did serve as a marker for synaptic density. It also revealed synaptic loss in three patients with epilepsy compared to healthy individuals.

“This is the first time we have synaptic density measurement in live human beings,” said Carson, who is senior author on the study. “Up to now any measurement of synaptic density was postmortem.”

The finding has several potential applications. With this noninvasive method, researchers may be able to follow the progression of many brain disorders, including epilepsy and Alzheimer’s disease, by measuring changes in synaptic density over time. Another application may be in assessing how pharmaceuticals slow the loss of neurons. “This opens the door to follow the natural evolution of synaptic density with normal aging and follow how drugs can alter synapses or synapse formation.”

Carson and his colleagues plan future studies involving PET imaging of synapses to research epilepsy and other brain disorders, including Alzheimer’s disease, schizophrenia, depression, and Parkinson’s disease. “There are many diseases where neuro-degeneration comes into play,” he noted.

About this neuroscience research article

Other authors on the study include Sjoerd J. Finnema, Nabeel B. Nabulsi, Tore Eid, Kamil Detyniecki, Shu-fei Lin, Ming-Kai Chen, Roni Dhaher, David Matuskey, Evan Baum, Daniel Holden, Dennis D. Spencer, Joël Mercier, Jonas Hannestad, and Yiyun Huang.

Funding: The study was supported in part by the Swebilius Foundation, UCB Pharma, and the National Center for Advancing Translational Science, a component of the National Institutes of Health. Mercier and Hannestad were employed by UCB Pharma at the time this work was planned, conducted, and analyzed.

Source: Jules Asher – Yale
Image Source: This NeuroscienceNews.com image is credited to Yale PET Center.
Original Research: Abstract for “Imaging synaptic density in the living human brain” by Sjoerd J. Finnema, Nabeel B. Nabulsi, Tore Eid, Kamil Detyniecki, Shu-fei Lin, Ming-Kai Chen, Roni Dhaher, David Matuskey, Evan Baum, Daniel Holden, Dennis D. Spencer, Joël Mercier, Jonas Hannestad, Yiyun Huang and Richard E. Carson in Science Translational Medicine. Published online July 20 2016 doi:10.1126/scitranslmed.aaf6667

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Yale. “Applying a New Imaging Tool to Common Brain Disorders.” NeuroscienceNews. NeuroscienceNews, 21 July 2016.
<https://neurosciencenews.com/neuroimaging-brain-disorders-4719/>.[/cbtab][cbtab title=”APA”]Yale. (2016, July 21). Applying a New Imaging Tool to Common Brain Disorders. NeuroscienceNew. Retrieved July 21, 2016 from https://neurosciencenews.com/neuroimaging-brain-disorders-4719/[/cbtab][cbtab title=”Chicago”]Yale. “Applying a New Imaging Tool to Common Brain Disorders.” https://neurosciencenews.com/neuroimaging-brain-disorders-4719/ (accessed July 21, 2016).[/cbtab][/cbtabs]


Abstract

Imaging synaptic density in the living human brain

Chemical synapses are the predominant neuron-to-neuron contact in the central nervous system. Presynaptic boutons of neurons contain hundreds of vesicles filled with neurotransmitters, the diffusible signaling chemicals. Changes in the number of synapses are associated with numerous brain disorders, including Alzheimer’s disease and epilepsy. However, all current approaches for measuring synaptic density in humans require brain tissue from autopsy or surgical resection. We report the use of the synaptic vesicle glycoprotein 2A (SV2A) radioligand [11C]UCB-J combined with positron emission tomography (PET) to quantify synaptic density in the living human brain. Validation studies in a baboon confirmed that SV2A is an alternative synaptic density marker to synaptophysin. First-in-human PET studies demonstrated that [11C]UCB-J had excellent imaging properties. Finally, we confirmed that PET imaging of SV2A was sensitive to synaptic loss in patients with temporal lobe epilepsy. Thus, [11C]UCB-J PET imaging is a promising approach for in vivo quantification of synaptic density with several potential applications in diagnosis and therapeutic monitoring of neurological and psychiatric disorders.

“Imaging synaptic density in the living human brain” by Sjoerd J. Finnema, Nabeel B. Nabulsi, Tore Eid, Kamil Detyniecki, Shu-fei Lin, Ming-Kai Chen, Roni Dhaher, David Matuskey, Evan Baum, Daniel Holden, Dennis D. Spencer, Joël Mercier, Jonas Hannestad, Yiyun Huang and Richard E. Carson in Science Translational Medicine. Published online July 20 2016 doi:10.1126/scitranslmed.aaf6667

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