PET imaging is a powerful tool for measuring physiological changes in the brain during deep brain stimulation (DBS). In this work, we acquired five PET scans using a highly selective D2/D3 dopamine antagonist, 18F-fallypride, to track changes in dopamine receptor availability, as measured by the distribution volume ratio (DVR), through the course of DBS in the bed nucleus of the stria terminalis (BNST) in a nonhuman primate. Methods: PET scans were performed on a rhesus monkey with unilateral BNST stimulation during periods of baseline, chronic high frequency (130 Hz) and low frequency (50 Hz) DBS stimulation, and during a washout period between stimulation periods. A final scan was performed with the electrode stimulation starting 110 min into the scan. Whole brain parametric images of 18F-fallypride DVR were calculated for each condition to track changes in both striatal and extrastriatal D2/D3 availability. Results: The monkey displayed significant increases in receptor binding throughout the brain during DBS relative to baseline for 130 and 50 Hz, with changes in DVR of: caudate 42%, 51%; putamen 56%, 57%; thalamus 33%, 49%; substantia nigra 29%, 26%; and prefrontal cortex 28%, 56%, respectively. Washout and post-stimulation scans revealed DVR values close to baseline values. Activating the stimulator midway through the final scan resulted in no statistically significant changes in binding. Conclusions: PET neuroligand imaging has demonstrated the sensitivity to track changes in dopamine D2/D3 binding during the course of DBS. These methods show great potential for providing insight into the neurochemical consequences of DBS.
Bibliographical noteFunding Information:
The authors would like to thank the following for their contributions to this research, making it possible: Wendy Newton and Vicky Carter for nonhuman primate handling and scheduling; Terry Oakes for help in image processing; as well as Dr. Erwin Montgomery and Dr. Ankur Garg for technical discussions and the journal reviewers. This material is based upon work supported in part by the Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs. N.T.V. was supported by NIH training grant T90 DK070079. The DBS electrodes were donated by Medtronic of Minneapolis, MN.
- Deep brain stimulation