Yanghong Yang1, Mika Naganawa1, Nora Hernadenz2, Neil Nguyen2, Nabeel Nabulsi1, Yiyun Huang1, Richard Carson1, David Matuskey1, Elan Louis2
1Department of Radiology and Biochemical Imaging, Yale University, 2University of Texas Southwestern Medical Center
Objective:
To utilize positron emission tomography (PET) imaging with the synaptic density tracer [11 C] UCB-J to characterize the distribution in the cerebellum and other brain areas in essential tremor (ET) compared to healthy controls (HC).
Background:
Numerous lines of evidence point to a cerebellar origins of ET, with a number of studies pointing to Purkinje cell loss. Studying potential markers of cell loss in vivo would be of great value. [11 C] UCB-J has been found to be an excellent tracer for quantitative imaging of synaptic vesicle glycoprotein 2A (SV2A), a marker of synaptic density, in the human brain. This tracer has not been used to study the ET brain.
Design/Methods:
Six individuals with ET with a mean age (SD) of 65 (10); three males), and sixteen demographically matched healthy comparison controls (HC; 63 (9); six males) participated in an [ 11 C] UCB-J PET scan. Binding potential value (BPND: binding potential of available receptors) was the primary outcome measure and using the centrum semiovale as the reference region. Muller Gartner partial volume correction (PVC) was applied to control for possible volumetric differences. T-tests were calculated for between group differences, and p values were uncorrected for multiple comparisons given the exploratory nature.
Results:
We observed significantly lower synaptic availability in ET compared to HC in the cerebellum (-11%, p=0.04), right cerebellum (-11%, p=0.03), vermis (-12%, p=0.04), motor cortex (-21%, p=0.001), and supplementary motor cortex (-20%, p=0.006).
Conclusions:
This in vivo investigation with [11 C] UCB-J PET in ET is the first sample to date (to our knowledge) and found preliminary evidence of lower synaptic availability in key brain areas. Additional data analysis is ongoing, such as applying Iterative-Yang PVC, correlating synaptic changes with clinical scores, and exploring network-based analyses.