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The response to rapid infusion of fentanyl in the human brain measured using pulsed arterial spin labelling

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Abstract

Objective

We evaluated the sensitivity of pulsed Arterial Spin Labelling (pASL) for the detection of changes in regional cerebral blood perfusion (CBP) during and after intra-venous (i.v.) infusion of an opioid agonist (fentanyl) and an opioid antagonist (naloxone).

Materials and methods

Twenty-three subjects were scanned four times, receiving i.v. infusion of fentanyl, naloxone, placebo and a second fentanyl administration, in four separate scanning sessions in randomised order. End-tidal CO2, respiration rate and heart rate were recorded continuously throughout each scan. pASL time series were collected using single shot EPI for 15 min (including 5 min of baseline prior to infusion).

Results

Significant increases in CBP were detected during and after administration of fentanyl, (when compared to placebo and naloxone), in most areas of high concentration of mu-opioid receptors (thalamus, lingual gyrus, para-hippocampal gyrus, and insula); near-significant increases were also observed in the insula. No increases in perfusion were observed during or after naloxone infusion. No correlation was found between regional rCBF changes and end-tidal CO2, respiration rate or heart rate. Good reliability was found between the first and second fentanyl sessions but the regions of high reliability did not overlap completely with those of highest perfusion change.

Conclusion

pASL is a suitable method for examining rapid, dynamic effects of opioid administration on brain physiology.

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Acknowledgments

The authors are grateful to Pfizer Pharmaceuticals UK for funding towards this project, to Mr Jeffrey Dalton for help with the implementation of software for the measurement of physiological variables and to Dr Eric Wong for providing a hyperbolic secant adiabatic RF pulse for use with arterial spin labelling.

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Authors and Affiliations

  1. Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King’s College London, De Crespigny Park, London, SE5 8AF, UK

    Fernando O. Zelaya, David J. Lythgoe, Sarah Lee, Caroline Andrews, Steven C. R. Williams & Mitul A. Mehta

  2. Department of Addictions, Institute of Psychiatry, King’s College London, De Crespigny Park, London, UK

    Christopher Muller-Pollard & Patricia Conrod

  3. Department of Addictive Behavior and Addiction Medicine, J5, 68159, Mannheim, Germany

    Evangelos Zois

  4. Neuropsychopharmacology Unit, Imperial College London, London, UK

    Laurence J. Reed

  5. Pfizer Global Research and Development, Sandwich, Kent, UK

    Trevor Smart & William Vennart

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  1. Fernando O. Zelaya
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  2. Evangelos Zois
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  3. Christopher Muller-Pollard
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  4. David J. Lythgoe
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  8. Patricia Conrod
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  10. Steven C. R. Williams
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  11. Mitul A. Mehta
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Corresponding author

Correspondence to Fernando O. Zelaya.

Additional information

M. A. Mehta and L. J. Reed contributed equally to this work.

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Zelaya, F.O., Zois, E., Muller-Pollard, C. et al. The response to rapid infusion of fentanyl in the human brain measured using pulsed arterial spin labelling. Magn Reson Mater Phy 25, 163–175 (2012). https://doi.org/10.1007/s10334-011-0293-4

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  • DOI: https://doi.org/10.1007/s10334-011-0293-4

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