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Research ArticleJPET Miniseries: Imaging

Potentials and Challenges for Arterial Spin Labeling in Pharmacological Magnetic Resonance Imaging

Danny J. J. Wang, Yufen Chen, María A. Fernández-Seara and John A. Detre
Journal of Pharmacology and Experimental Therapeutics May 2011, 337 (2) 359-366; DOI: https://doi.org/10.1124/jpet.110.172577
Danny J. J. Wang
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Yufen Chen
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María A. Fernández-Seara
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John A. Detre
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Abstract

Pharmacological magnetic resonance imaging (phMRI) is increasingly being used in drug discovery and development to speed the translation from the laboratory to the clinic. The two primary methods in phMRI include blood-oxygen-level-dependent (BOLD) contrast and arterial spin-labeled (ASL) perfusion MRI. BOLD contrast has been widely applied in existing phMRI studies. However, because of the lack of absolute quantification and poor reproducibility over time scales longer than hours or across scanning sessions, BOLD fMRI may not be suitable to track oral and other long-term drug effects on baseline brain function. As an alternative method, ASL provides noninvasive, absolute quantification of cerebral blood flow both at rest and during task activation. ASL perfusion measurements have been shown to be highly reproducible over minutes and hours to days and weeks. These two characteristics make ASL an ideal tool for phMRI for studying both intravenous and oral drug action as well as understanding drug effects on baseline brain function and brain activation to cognitive or sensory processing. When ASL is combined with BOLD fMRI, drug-induced changes in cerebral metabolic rate of oxygen may also be inferred. Representative phMRI studies using ASL perfusion MRI on caffeine, remifentanil, and metoclopramide (dopamine antagonist) are reviewed here, with an emphasis on the methodologies used to control for potentially confounding vascular and systemic effects. Both the potentials and limitations of using ASL as an imaging marker of drug action are discussed.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of Mental Health [Grants MH080892, MH080729]; the National Institutes of Health National Center for Research Resources [Grant RR002305]; the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS058386]; the National Institutes of Health National Institute on Aging [Grant AG01657011A]; and the American Recovery and Reinvestment Act [Grant MH080892S1].

  • J.A.D. is an inventor on the University of Pennsylvania's patent for ASL MRI and is entitled to institutional royalty sharing for its licensure. D.J.J.W. is a consultant for Pfizer Inc.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.172577.

  • ABBREVIATIONS:

    PET
    positron emission tomography
    ASL
    arterial spin labeled
    CASL
    continuous ASL
    pCASL
    pseudo-CASL
    PASL
    pulsed ASL
    BOLD
    blood-oxygen-level-dependent
    MRI
    magnetic resonance imaging
    phMRI
    pharmacological MRI
    fMRI
    functional MRI
    CBF
    cerebral blood flow
    3D
    three-dimensional
    GRASE
    gradient and spin echo
    BS
    background suppression
    PC
    phase-contrast
    ICC
    intraclass correlation coefficient
    CMRO2
    cerebral metabolic rate of oxygen
    CMRGlu
    cerebral metabolic rate of glucose
    OEF
    oxygen extraction fraction
    ATT
    arterial transit time
    ROI
    region of interest
    PaCO2
    partial pressure of carbon dioxide in the arterial blood.

  • Received July 9, 2010.
  • Accepted December 2, 2010.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 381 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 381, Issue 2
1 May 2022
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Research ArticleJPET Miniseries: Imaging

Potentials and Challenges for Arterial Spin Labeling in Pharmacological Magnetic Resonance Imaging

Danny J. J. Wang, Yufen Chen, María A. Fernández-Seara and John A. Detre
Journal of Pharmacology and Experimental Therapeutics May 1, 2011, 337 (2) 359-366; DOI: https://doi.org/10.1124/jpet.110.172577

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Research ArticleJPET Miniseries: Imaging

Potentials and Challenges for Arterial Spin Labeling in Pharmacological Magnetic Resonance Imaging

Danny J. J. Wang, Yufen Chen, María A. Fernández-Seara and John A. Detre
Journal of Pharmacology and Experimental Therapeutics May 1, 2011, 337 (2) 359-366; DOI: https://doi.org/10.1124/jpet.110.172577
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