Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 40, Issue 9, Pages 1890-1901Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X19879230
Keywords
Ordered subset expectation maximization reconstruction; positron emission tomography; reference region; synaptic vesicle glycoprotein 2A; synaptic density
Categories
Funding
- NINDS [R01NS094253]
- NIA [R01AG052560]
- UCB Pharma
- CTSA Grant from the National Center for Advancing Translational Science, a component of the NIH [UL1 TR000142]
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C-11-UCB-J is a positron emission tomography (PET) radioligand that has been used in humans for synaptic vesicle glycoprotein 2A (SV2A) imaging and as a potential synaptic density marker. The centrum semiovale (CS) is a proposed reference region for noninvasive quantification of C-11-UCB-J, due to negligible concentrations of SV2A in this region in baboon brain assessed by in vitro methods. However, in displacement scans with SV2A-specific drug levetiracetam in humans, a decrease in C-11-UCB-J concentration was observed in the CS, consistent with some degree of specific binding. The current study aims to validate the CS as a reference region by (1) optimizing CS region of interest (ROI) to minimize spill-in from gray matter with high radioactivity concentrations; (2) investigating convergence of CS ROI values using ordered subset expectation maximization (OS-EM) reconstruction, and (3) comparing baseline CS volume of distribution (V-T) to nondisplaceable uptake in gray matter, V-ND. Improving ROI definition and increasing OS-EM iterations during reconstruction decreased the difference between CS V-T and V-ND. However, even with these corrections, CS V-T overestimated V-ND by similar to 35-40%. These measures showed significant correlation, suggesting that, though biased, the CS may be a useful estimate of nondisplaceable uptake, allowing for noninvasive quantification for SV2A PET.
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