Los Angeles -- A new PET imaging approach that
measures synaptic density in the spinal cord provides a quantitative way to
assess the brain's functional wiring in patients with multiple sclerosis. With
this personalized information, physicians can monitor disease progression and evaluate
whether new treatments are working to protect or restore these critical
connections. This research was presented at the Society of Nuclear Medicine and
Molecular Imaging's 2026 Annual Meeting.
Multiple sclerosis is a condition that affects millions of
people worldwide and can cause physical disability, fatigue, and cognitive
impairment. While multiple sclerosis is traditionally viewed as a disease that
damages the protective coating of nerves, there is also another, more subtle
type of damage: the loss of synapses, which are the vital connection points
where brain cells communicate.
"Although the spinal cord is a primary and often early site
of inflammatory and neurodegenerative pathology in multiple sclerosis, in vivo
quantification of synaptic density in this region has not yet been explored," said Pou Hong Justin Chia, a graduate student at the Centre for Addiction and
Mental Health at the University of Toronto, the lead presenter of the study. "To address this knowledge
gap, my colleagues and I investigated a specialized imaging technique called
SV2A PET to visualize and quantify this loss of connections in the spinal cord
of a mouse model of multiple sclerosis
and, crucially, in the brains and spinal cords of living multiple sclerosis
patients."
In the study, researchers conducted 18F-SynVesT-1 PET scans in mice with experimental autoimmune encephalomyelitis, a widely used mouse
model of multiple sclerosis,
and in healthy control mice. Spinal cord regions of
interest were defined, and total volume of distribution and radiotracer binding were quantified and compared between groups. To
provide a translational context, 11C-UCB-J PET imaging was performed on six multiple
sclerosis patients and six healthy controls in collaboration with Yale University. Total volume of
distribution maps were generated and human PET data
were compared.
In the multiple sclerosis-model mice, 18F-SynVesT-1 PET
successfully detected significant reductions in synaptic density within specific regions of the spinal cord,
which were corroborated by binding studies. In the human PET study, multiple
sclerosis patients exhibited a 16.4 percent reduction in 11C-UCB-J binding
across the brain as compared to healthy controls. Widespread reductions were
also observed in subcortical and spinal cord regions, mirroring the extensive
synaptic pathology seen in the preclinical model.
"This work represents an important step toward applying SV2A PET to quantify synaptic
pathology in multiple sclerosis across
preclinical and human studies," said Chao Zheng, PhD, senior author and
principal investigator of the study,
based at the Centre for Addiction and Mental Health and the University
of Toronto. "Our team demonstrated that SV2A PET can detect spinal cord
synaptic loss in a mouse model of multiple sclerosis and led the translational
framework linking these findings to pilot human multiple sclerosis PET imaging.
Together, these cross-species data support SV2A PET as a quantitative tool for
monitoring synaptic pathology and evaluating future therapeutic strategies."
According to Chia, this research provides direct evidence in
living subjects that synaptic loss is a widespread feature of multiple
sclerosis. "Understanding how and where these connections are lost can help
explain the symptoms patients experience and give doctors and researchers a
more sensitive way to detect disease-related changes, monitor progression over
time, and better understand how multiple sclerosis and other neurological
diseases affect the brain and spinal
cord," he said.
Currently, SV2A PET imaging in multiple sclerosis is
available for clinical trials at specialized academic centers. While it is not
yet a routine part of standard clinical care, the data from this pilot study is
a necessary step toward larger clinical trials. If validated in larger studies, this imaging approach could be integrated into clinical practice and
drug development over the next several years.