TY - JOUR
T1 - PET measurement of changes in D2/D3 dopamine receptor binding in a nonhuman primate during chronic deep brain stimulation of the bed nucleus of the stria terminalis
AU - Vandehey, Nicholas T.
AU - Garell, P. Charles
AU - Hampel, Joseph A.
AU - Murali, Dhanabalan
AU - Smith, Elizabeth M.
AU - Davidson, Richard
AU - Converse, Alexander K.
AU - Nickles, R. Jerry
AU - Christian, Bradley T.
PY - 2009/1/30
Y1 - 2009/1/30
N2 - 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.
AB - 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.
KW - BNST
KW - D2/D3
KW - DBS
KW - Deep brain stimulation
KW - Dopamine
KW - Fallypride
KW - PET
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U2 - 10.1016/j.jneumeth.2008.08.033
DO - 10.1016/j.jneumeth.2008.08.033
M3 - Article
C2 - 18824196
AN - SCOPUS:57649178918
VL - 176
SP - 129
EP - 135
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
IS - 2
ER -