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

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.

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

“…Another strength is the investigation of medication-induced alterations in CBF. Few fMRI studies effectively test medication-related CBF changes despite evidence of an interaction between basal physiologic and metabolic states and task-induced BOLD changes (Wang et al, 2011). The well-ascertained and clinically representative sample of individuals with methamphetamine use disorder also represents a strength, as it is often difficult to recruit individuals with severe drug addiction for clinical neuroscience research, yet these are precisely the individuals with which addiction science aims to help.…”

Baseline brain perfusion and brain structure in patients with major depression: a multimodal magnetic resonance imaging study

“…It is important to note that CASL is a relatively new technique compared with PET, SPECT or even BOLD fMRI, 72 which might partly account for the lack of clinically relevant data in psychiatric samples 73 acquired with this specific method. Also, findings obtained under resting-state conditions do not necessarily imply either intact or deficient function of distinct brain regions when active cognitive, social or affective processing is required.…”

Optimization and Reliability of Multiple Postlabeling Delay Pseudo-Continuous Arterial Spin Labeling during Rest and Stimulus-Induced Functional Task Activation

“…6,8 While the exact dynamic relationship between neural function and CBF is not yet well known, considerable evidence suggests that imaging CBF alone offers a strong correlate of brain function. [9][10][11] While it has been shown that ASL provides an effective tool for rapid and safe estimation of blood flow in resting, task-related, and pharmacological functional MRI (FMRI) studies; 4,12,13 only a few studies have investigated how reliable these measures are and fewer still have looked at ways to improve this. For example, continuous ASL (CASL) techniques have been shown to be accurate and highly reproducible within 1-hour 14 and 7-week timeframes.…”