Abstract
Pharmacological MRI (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, due to 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, hours to days and weeks. These two characteristics make ASL an ideal tool for phMRI to study both intravenous and oral drug action as well as to understand drug effects on baseline brain function and on brain activation to cognitive or sensory processing. When ASL is combined with BOLD fMRI, drug induced changes in cerebral metabolic rate of oxygen (CMRO2) 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.
- Arterial Spin Labeling (ASL)
- Blood Oxygen Level Dependent (BOLD)
- Caffeine
- Perfusion MRI
- Pharmacological MRI (phMRI)
- Remifentanil
- Received July 9, 2010.
- Revision received December 1, 2010.
- Accepted December 2, 2010.
- The American Society for Pharmacology and Experimental Therapeutics