title: Simultaneous fMRI-PET of the opioidergic pain system in human brain.
abstract: MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET data were acquired with an opioid radioligand, [(11)C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting that pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo.
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: wey@nmr.mgh.harvard.edu.
authors.forename: Hsiao-Ying
authors.initials: HY
authors.lastname: Wey
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Darin D
authors.initials: DD
authors.lastname: Dougherty
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California at Los Angeles, CA 90095, USA.
authors.forename: Danny J J
authors.initials: DJ
authors.lastname: Wang
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Chonde
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosen
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.affiliation: Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: kongj@nmr.mgh.harvard.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D001931:Brain Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004174:Diprenorphine; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009292:Narcotic Antagonists; D010146:Pain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D011957:Receptors, Opioid / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D004174:Diprenorphine
keywords: Hemodynamic response; Neurotransmission; Opioid receptor; Pain; Simultaneous MRI/PET
references.citation: Pain. 1978 Jun;5(1):19-29
references.pmid: 673439
references.citation: Pain. 2007 Jan;127(1-2):183-94
references.pmid: 17137714
references.citation: J Cereb Blood Flow Metab. 2002 Dec;22(12):1440-52
references.pmid: 12468889
references.citation: Behav Brain Res. 2010 Aug 25;211(2):215-9
references.pmid: 20347878
references.citation: J Pain. 2009 Nov;10(11):1113-20
references.pmid: 19878862
references.citation: Neuroimage. 2012 Aug 15;62(2):782-90
references.pmid: 21979382
references.citation: Hum Brain Mapp. 2006 Sep;27(9):715-21
references.pmid: 16342273
references.citation: Anesthesiology. 2007 Mar;106(3):548-56
references.pmid: 17325514
references.citation: Hum Brain Mapp. 1997;5(4):238-42
references.pmid: 20408222
references.citation: AJNR Am J Neuroradiol. 1999 Apr;20(4):686-90
references.pmid: 10319982
references.citation: Neuroimage. 2012 Aug 15;62(2):1072-85
references.pmid: 22495143
references.citation: Brain. 2008 May;131(Pt 5):1171-96
references.pmid: 18048446
references.citation: Eur J Pharmacol. 2003 Jan 17;459(2-3):217-9
references.pmid: 12524149
references.citation: Pain. 2002 Oct;99(3):589-598
references.pmid: 12406535
references.citation: Exp Neurol. 2012 Apr;234(2):382-8
references.pmid: 22245158
references.citation: J Neurosci. 2013 Sep 11;33(37):14729-37
references.pmid: 24027273
references.citation: Pain. 2010 Feb;148(2):257-267
references.pmid: 20005043
references.citation: J Neurosci. 2002 Aug 1;22(15):6773-80
references.pmid: 12151557
references.citation: Nat Neurosci. 2007 Dec;10(12):1515-7
references.pmid: 17982452
references.citation: J Neurosci. 2008 Dec 3;28(49):13354-62
references.pmid: 19052227
references.citation: Synapse. 2007 Sep;61(9):707-14
references.pmid: 17559096
references.citation: J Neurosci Methods. 1994 Mar;51(2):123-34
references.pmid: 8051944
references.citation: J Cereb Blood Flow Metab. 1997 Sep;17(9):932-42
references.pmid: 9307606
references.citation: Neuroimage. 2007 Feb 1;34(3):1042-53
references.pmid: 17169578
references.citation: Nat Rev Neurosci. 2008 Apr;9(4):314-20
references.pmid: 18354400
references.citation: Hum Brain Mapp. 2012 Feb;33(2):455-65
references.pmid: 21416560
references.citation: J Nucl Med. 2012 Dec;53(12):1916-25
references.pmid: 23143086
references.citation: Med Image Anal. 2001 Jun;5(2):143-56
references.pmid: 11516708
references.citation: Hum Brain Mapp. 2002 Nov;17(3):143-55
references.pmid: 12391568
references.citation: Synapse. 2002 Jul;45(1):25-30
references.pmid: 12112410
references.citation: Pain. 2006 May;122(1-2):63-7
references.pmid: 16527398
references.citation: J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40
references.pmid: 8784228
references.citation: Neuron. 2007 Aug 2;55(3):377-91
references.pmid: 17678852
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5069-73
references.pmid: 22411802
references.citation: Cereb Cortex. 2004 Jan;14(1):11-22
references.pmid: 14654453
references.citation: Hum Brain Mapp. 2007 Nov;28(11):1194-205
references.pmid: 17266101
references.citation: J Nucl Med. 2006 Dec;47(12):1968-76
references.pmid: 17138739
references.citation: J Nucl Med. 2012 Jun;53(6):845-55
references.pmid: 22534830
references.citation: Science. 2001 Jul 13;293(5528):311-5
references.pmid: 11452128
references.citation: Neuroimage. 2002 Oct;17(2):825-41
references.pmid: 12377157
references.citation: Neuroimage. 2009 Oct 15;48(1):63-72
references.pmid: 19573611
references.citation: J Cereb Blood Flow Metab. 2000 Mar;20(3):423-51
references.pmid: 10724107
references.citation: Brain Res. 1986 Nov 12;397(2):395-400
references.pmid: 3801880
references.citation: J Neurosci. 2006 Jan 11;26(2):381-8
references.pmid: 16407533