Skip to main content
SpringerLink
Log in

Magnetic Resonance Imaging of Pharmacological Systems

  • Chapter
  • First Online:
Imaging in CNS Drug Discovery and Development

  • 638 Accesses

Abstract

With the appropriate hardware, pulse sequences and analysis methods, modern MRI research is able to measure numerous neurobiologically relevant parameters including functional activation (fMRI) using blood oxygen level dependent, diffusion tensor imaging – either to measure integrity of white matter or to follow white matter fiber tracts, MR spectroscopy, changes in cerebral blood flow, cerebral blood volume and oxygen metabolism (CMRO2) and of course its more traditional applications to measure, qualitatively and recently quantitatively, brain anatomy. More recently, investigators have added various pharmacological probes to research paradigms to better mechanistically understand both the healthy and diseased brain. This chapter outlines some of the issues related to using pharmacological agents in MRI studies, some of the research question applications, limitations and potential pitfalls.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aguirre GK, Detre JA, Zarahn E et al (2002) Experimental design and the relative sensitivity of BOLD and perfusion fMRI. Neuroimage 15:488–500

    Article  PubMed  CAS  Google Scholar 

  • Biswal B, Yetkin FZ, Haughton VM et al (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34:537–541

    Article  PubMed  CAS  Google Scholar 

  • Bloom AS, Hoffmann RG, Fuller SA et al (1999) Determination of drug-induced changes in functional MRI signal using a pharmacokinetic model. Hum Brain Mapp 8:235–244

    Article  PubMed  CAS  Google Scholar 

  • Breiter HC, Gollub RL, Weisskoff RM et al (1997) Acute effects of cocaine on human brain activity and emotion. Neuron 19:591–611

    Article  PubMed  CAS  Google Scholar 

  • Calhoun VD, Adali T, Pearlson GD et al (2001) A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp 14:140–151

    Article  PubMed  CAS  Google Scholar 

  • Choi JK, Chen YI, Hamel E et al (2006) Brain hemodynamic changes mediated by dopamine receptors: role of the cerebral microvasculature in dopamine-mediated neurovascular coupling. NeuroImage 30:700–712

    Article  PubMed  Google Scholar 

  • Comon P (1994) Independent component analysis, a new concept. Signal Processing 36:287–314

    Article  Google Scholar 

  • Cotzias GC, Horiuchi K, Fuenzalida S et al (1968) Chronic manganese poisoning. Clearance of tissue manganese concentrations with persistance of the neurological picture. Neurology 18:376–382

    PubMed  CAS  Google Scholar 

  • Dacey RG Jr, Bassett JE, Takayasu M (1988) Vasomotor responses of rat intracerebral arterioles to vasoactive intestinal peptide, substance P, neuropeptide Y, and bradykinin. J Cereb Blood Flow Metab 8:254–261

    Article  PubMed  CAS  Google Scholar 

  • Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711

    Article  PubMed  CAS  Google Scholar 

  • Friston KJ, Williams S, Howard R et al (1996) Movement-related effects in fMRI time-series. Magn Reson Med 35:346–355

    Article  PubMed  CAS  Google Scholar 

  • Glover GH, Li TQ, Ress D (2000) Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med 44:162–167

    Article  PubMed  CAS  Google Scholar 

  • Gollub RL, Breiter HC, Kantor H et al (1998) Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects. J Cereb Blood Flow Metab 18:724–734

    Article  PubMed  CAS  Google Scholar 

  • Hahn B, Ross TJ, Yang Y et al (2007) Nicotine enhances visuospatial attention by deactivating areas of the resting brain default network. J Neurosci 27:3477–3489

    Article  PubMed  CAS  Google Scholar 

  • Herkenham M (1987) Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. Neuroscience 23:1–38

    Article  PubMed  CAS  Google Scholar 

  • Hoge RD, Atkinson J, Gill B et al (1999) Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. Proc Natl Acad Sci USA 96:9403–9408

    Article  PubMed  CAS  Google Scholar 

  • Honey G, Bullmore E (2004) Human pharmacological MRI. Trends Pharmacol Sci 25:366–374

    Article  PubMed  CAS  Google Scholar 

  • Hong LE, Gu H, Yang Y, et al (2008) Nicotine addiction and nicotine’s action are associated with separate cingulate functional circuits. Arch Gen Psychiatry 66(4):431–441

    Article  Google Scholar 

  • Hudetz AG, Biswal BB, Shen H et al (1998) Spontaneous fluctuations in cerebral oxygen supply. An introduction. Adv Exp Med Biol 454:551–559

    PubMed  CAS  Google Scholar 

  • Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 5:347–360

    Article  PubMed  CAS  Google Scholar 

  • Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10:1369–1376

    Article  PubMed  CAS  Google Scholar 

  • Jenkins BG, Sanchez-Pernaute R, Brownell AL et al (2004) Mapping dopamine function in primates using pharmacologic magnetic resonance imaging. J Neurosci 24:9553–9560

    Article  PubMed  CAS  Google Scholar 

  • Kim SG, Rostrup E, Larsson HB et al (1999) Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation. Magn Reson Med 41:1152–1161

    Article  PubMed  CAS  Google Scholar 

  • Krimer LS, Muly EC III, Williams GV et al (1998) Dopaminergic regulation of cerebral cortical microcirculation. Nat Neurosci 1:286–289

    Article  PubMed  CAS  Google Scholar 

  • Lawrence NS, Ross TJ, Stein EA (2002) Cognitive mechanisms of nicotine on visual attention. Neuron 36:539–548

    Article  PubMed  CAS  Google Scholar 

  • Lin YJ, Koretsky AP (1997) Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function. Magn Reson Med 38:378–388

    Article  PubMed  CAS  Google Scholar 

  • Logothetis NK, Pauls J, Augath M et al (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature 412:150–157

    Article  PubMed  CAS  Google Scholar 

  • Lu H, Golay X, Pekar JJ et al (2003) Functional magnetic resonance imaging based on changes in vascular space occupancy. Magn Reson Med 50:263–274

    Article  PubMed  Google Scholar 

  • Lu H, Patel S, Luo F et al (2004) Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation with neuronal activity localized by Fos expression. Magn Reson Med 52:1060–1068

    Article  PubMed  Google Scholar 

  • Lu H, Scholl CA, Zuo Y et al (2007a) Quantifying the blood oxygenation level dependent effect in cerebral blood volume-weighted functional MRI at 9.4T. Magn Reson Med 58:616–621

    Article  PubMed  Google Scholar 

  • Lu H, Xi ZX, Gitajn L et al (2007b) Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI). Proc Natl Acad Sci USA 104:2489–2494

    Article  PubMed  CAS  Google Scholar 

  • Lu H, Zuo Y, Gu H et al (2007c) Synchronized delta oscillations correlate with the resting-state functional MRI signal. Proc Natl Acad Sci USA 104:18265–18269

    Article  PubMed  CAS  Google Scholar 

  • Mandeville JB, Marota JJ, Kosofsky BE et al (1998) Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation. Magn Reson Med 39:615–624

    Article  PubMed  CAS  Google Scholar 

  • Marota JJ, Mandeville JB, Weisskoff RM et al (2000) Cocaine activation discriminates dopaminergic projections by temporal response: an fMRI study in Rat. Neuroimage 11:13–23

    Article  PubMed  CAS  Google Scholar 

  • McKeown MJ, Makeig S, Brown GG et al (1998) Analysis of fMRI data by blind separation into independent spatial components. Hum Brain Mapp 6:160–188

    Article  PubMed  CAS  Google Scholar 

  • McKie S, Del Ben C, Elliott R et al (2005) Neuronal effects of acute citalopram detected by pharmacoMRI. Psychopharmacology (Berl) 180:680–686

    Article  CAS  Google Scholar 

  • Mendonca-Dias MH, Gaggelli E, Lauterbur PC (1983) Paramagnetic contrast agents in nuclear magnetic resonance medical imaging. Semin Nucl Med 13:364–376

    Article  PubMed  CAS  Google Scholar 

  • Nehlig A, Daval JL, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev 17:139–170

    Article  PubMed  CAS  Google Scholar 

  • Ogawa S, Menon RS, Tank DW et al (1993) Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J 64:803–812

    Article  PubMed  CAS  Google Scholar 

  • Raichle ME, Hartman BK, Eichling JO et al (1975) Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Natl Acad Sci USA 72:3726–3730

    Article  PubMed  CAS  Google Scholar 

  • Reinhard JF Jr, Liebmann JE, Schlosberg AJ et al (1979) Serotonin neurons project to small blood vessels in the brain. Science 206:85–87

    Article  PubMed  CAS  Google Scholar 

  • Risinger RC, Salmeron BJ, Ross TJ et al (2005) Neural correlates of high and craving during cocaine self-administration using BOLD fMRI. Neuroimage 26:1097–1108

    Article  PubMed  Google Scholar 

  • Rostrup E, Larsson HB, Toft PB et al (1994) Functional MRI of CO2 induced increase in cerebral perfusion. NMR Biomed 7:29–34

    Article  PubMed  CAS  Google Scholar 

  • Roy CS, Sherrington CS (1890) On the Regulation of the Blood-supply of the Brain. J Physiol 11:85–158

    PubMed  CAS  Google Scholar 

  • Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nat Neurosci 10:1110–1115

    Article  PubMed  CAS  Google Scholar 

  • Saleem KS, Pauls JM, Augath M et al (2002) Magnetic resonance imaging of neuronal connections in the macaque monkey. Neuron 34:685–700

    Article  PubMed  CAS  Google Scholar 

  • Salmeron BJ, Stein EA (2002) Pharmacological applications of magnetic resonance imaging. Psychopharmacol Bull 36:102–129

    PubMed  Google Scholar 

  • Sato A, Sato Y (1992) Regulation of regional cerebral blood flow by cholinergic fibers originating in the basal forebrain. Neurosci Res 14:242–274

    Article  PubMed  CAS  Google Scholar 

  • Silva AC, Bock NA (2008) Manganese-enhanced MRI: an exceptional tool in translational neuroimaging. Schizophr Bull 34:595–604

    Article  PubMed  Google Scholar 

  • Sokoloff L (1976) [1–14C]-2-deoxy-d-glucose method for measuring local cerebral glucose utilization. Mathematical analysis and determination of the “lumped” constants. Neurosci Res Program Bull 14:466–468

    PubMed  CAS  Google Scholar 

  • Stein EA, Pankiewicz J, Harsch HH et al (1998) Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. Am J Psychiatry 155:1009–1015

    PubMed  CAS  Google Scholar 

  • Takeda A, Ishiwatari S, Okada S (1998) In vivo stimulation-induced release of manganese in rat amygdala. Brain Res 811:147–151

    Article  PubMed  CAS  Google Scholar 

  • Vincent JL, Patel GH, Fox MD et al (2007) Intrinsic functional architecture in the anaesthetized monkey brain. Nature 447:83–86

    Article  PubMed  CAS  Google Scholar 

  • Wise RG, Tracey I (2006) The role of fMRI in drug discovery. J Magn Reson Imaging 23:862–876

    Article  PubMed  Google Scholar 

  • Wise RG, Rogers R, Painter D et al (2002) Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by remifentanil. Neuroimage 16:999–1014

    Article  PubMed  Google Scholar 

  • Yang Y, Gu H, Stein EA (2004) Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation. Magn Reson Med 52:1407–1417

    Article  PubMed  Google Scholar 

  • Zhao F, Wang P, Hendrich K et al (2005) Spatial specificity of cerebral blood volume-weighted fMRI responses at columnar resolution. Neuroimage 27:416–424

    Article  PubMed  CAS  Google Scholar 

  • Zonta M, Angulo MC, Gobbo S et al (2003) Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6:43–50

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Institute on Drug Abuse, Intramural Research Program, Neuroimaging Research Branch, National Institutes of Health, Baltimore, MD, 21224, USA

    Elliot A. Stein

Authors
  1. Hanbing Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas J. Ross
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elliot A. Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elliot A. Stein .

Editor information

Editors and Affiliations

  1. Mill Street 115, Belmont, 02478, U.S.A.

    David Borsook

  2. Mill Street 115, Belmont, 02478, U.S.A.

    Lino R. Beccera

  3. Dept. Psychiatry, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom

    Edward Bullmore

  4. Sumneytown Pike , West Point, 19486, U.S.A.

    Richard J. Hargreaves

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Lu, H., Ross, T.J., Stein, E.A. (2010). Magnetic Resonance Imaging of Pharmacological Systems. In: Borsook, D., Beccera, L., Bullmore, E., Hargreaves, R. (eds) Imaging in CNS Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0134-7_6

Download citation

Publish with us

Policies and ethics

Search

Navigation