Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model

Background: Subthalamic high-frequency deep brain stimulation (STN DBS) has during the last decade been widely used in the treatment of Parkinson's disease (PD) complicated by motor fluctuations and medicine-induced adverse effects. The exact mechanism of STN DBS is, however, still unelucidated. Objective: To evaluate whether STN DBS changes regional cerebral blood flow (rCBF) and oxygen consumption, by positron emission tomography (PET) in a non-primate large animal PD model of STN DBS. Methods: Three MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intoxicated female Göttingen minipigs (age 8-12 months, weight 16-20 kg) were stereotaxically implanted unilaterally with a DBS electrode (Medtronic, model 3387) connected to a pulse generator (Medtronic, model 7424) placed subcutaneously in the neck region. Four to six weeks later the animals were anesthetized and placed in a PET scanner. Three water (H₂¹⁵O) and three oxygen (¹⁵O₂) scans were performed, before stimulation with clinical parametres (continuous unipolar stimulation (electrode negative, case positive), amplitude 3V, frequency 160 Hz, and pulse-width 60 μs) was initiated and followed by 5 water and oxygen scans 5, 30, 60, 120 and 240 min thereafter. The obtained data (the three baseline scans versus the five poststimulation scans) were analysed by parametric DOT-analysis after semiautomatic coregistration to an average MRI pig brain. Results: rCBF was significantly increased (t-value = 5.47, p-value < 0.05) at the electrode tip after initiation of stimulation, and non-significant increases of oxygen consumption occurred in the ipsilateral- (t-value = 3.67, p-value < 0.1), and contralateral cortex (t-value = 3.34, p-value < 0.1). Conclusion: Our results indicate that STN DBS increases local midbrain rCBF and oxygen consumption in centrally placed cortical areas. The minipig may thus be a well-suited animal model for further studies of the mechanism of STN DBS in PD.