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

Mette S. Nielsen, Flemming Andersen, Paul Cumming, Arne Møller, Albert Gjedde, Jens C. Sørensen, Carsten R. Bjarkam

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.

Original languageEnglish (US)
Title of host publicationDeep Brain Stimulation: New Developments, Procedures and Applications
PublisherNova Science Publishers, Inc.
Pages141-157
Number of pages17
ISBN (Print)9781619425996
StatePublished - 2012
Externally publishedYes

Fingerprint

Deep Brain Stimulation
Positron-Emission Tomography
Cerebrovascular Circulation
Swine
Regional Blood Flow
Oxygen Consumption
Parkinson Disease
Miniature Swine
Electrodes
Oxygen
Animal Disease Models
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Water
Mesencephalon
Neck
Animal Models
Medicine
Weights and Measures
Brain

Keywords

  • Animal model
  • Basal ganglia
  • Cerebral oxygen consumption
  • Göttingen minipig
  • MPTP
  • Regional cerebral blood flow (rCBF)

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

Cite this

Nielsen, M. S., Andersen, F., Cumming, P., Møller, A., Gjedde, A., Sørensen, J. C., & Bjarkam, C. R. (2012). Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model. In Deep Brain Stimulation: New Developments, Procedures and Applications (pp. 141-157). Nova Science Publishers, Inc..

Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model. / Nielsen, Mette S.; Andersen, Flemming; Cumming, Paul; Møller, Arne; Gjedde, Albert; Sørensen, Jens C.; Bjarkam, Carsten R.

Deep Brain Stimulation: New Developments, Procedures and Applications. Nova Science Publishers, Inc., 2012. p. 141-157.

Research output: Chapter in Book/Report/Conference proceedingChapter

Nielsen, MS, Andersen, F, Cumming, P, Møller, A, Gjedde, A, Sørensen, JC & Bjarkam, CR 2012, Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model. in Deep Brain Stimulation: New Developments, Procedures and Applications. Nova Science Publishers, Inc., pp. 141-157.
Nielsen MS, Andersen F, Cumming P, Møller A, Gjedde A, Sørensen JC et al. Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model. In Deep Brain Stimulation: New Developments, Procedures and Applications. Nova Science Publishers, Inc. 2012. p. 141-157
Nielsen, Mette S. ; Andersen, Flemming ; Cumming, Paul ; Møller, Arne ; Gjedde, Albert ; Sørensen, Jens C. ; Bjarkam, Carsten R. / Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model. Deep Brain Stimulation: New Developments, Procedures and Applications. Nova Science Publishers, Inc., 2012. pp. 141-157
@inbook{9751818bc27b45b7a24737e6e3523234,
title = "Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model",
abstract = "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 G{\"o}ttingen 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.",
keywords = "Animal model, Basal ganglia, Cerebral oxygen consumption, G{\"o}ttingen minipig, MPTP, Regional cerebral blood flow (rCBF)",
author = "Nielsen, {Mette S.} and Flemming Andersen and Paul Cumming and Arne M{\o}ller and Albert Gjedde and S{\o}rensen, {Jens C.} and Bjarkam, {Carsten R.}",
year = "2012",
language = "English (US)",
isbn = "9781619425996",
pages = "141--157",
booktitle = "Deep Brain Stimulation: New Developments, Procedures and Applications",
publisher = "Nova Science Publishers, Inc.",

}

TY - CHAP

T1 - Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine Parkinson model

AU - Nielsen, Mette S.

AU - Andersen, Flemming

AU - Cumming, Paul

AU - Møller, Arne

AU - Gjedde, Albert

AU - Sørensen, Jens C.

AU - Bjarkam, Carsten R.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Animal model

KW - Basal ganglia

KW - Cerebral oxygen consumption

KW - Göttingen minipig

KW - MPTP

KW - Regional cerebral blood flow (rCBF)

UR - http://www.scopus.com/inward/record.url?scp=84892037752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892037752&partnerID=8YFLogxK

M3 - Chapter

SN - 9781619425996

SP - 141

EP - 157

BT - Deep Brain Stimulation: New Developments, Procedures and Applications

PB - Nova Science Publishers, Inc.

ER -