Quantification of cerebral blood flow as biomarker of drug effect: Arterial spin labeling phMRI after a single dose of oral citalopram

Y. Chen*, H. I. Wan, J. P. O'Reardon, D. J J Wang, Z. Wang, M. Korczykowski, J. A. Detre

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Arterial spin labeling (ASL) allows noninvasive quantification of cerebral blood flow (CBF), which can be used as a biomarker of drug effects in pharmacological magnetic resonance imaging (phMRI). In a double-blind, placebo-controlled crossover study, we investigated the effects of a single oral dose of citalopram (20mg) on resting CBF in 12 healthy subjects, using ASL phMRI. Support-vector machine (SVM) analysis detected significant drug-induced reduction in CBF in brain regions including the amygdala, fusiform gyrus, insula, and orbitofrontal cortex. These regions have been shown to have abnormally elevated CBF in patients with major depression, as well as in subjects genetically prone to depression. Mixed-effects analysis on data extracted from selected regions of interest (ROIs) revealed significant drug effect only in serotonergic areas of the brain (z = 4.45, P< 0.005). These results demonstrate the utility of ASL phMRI as a biomarker of pharmacological activity of orally administered drugs in the brain.

Original languageEnglish (US)
Pages (from-to)251-258
Number of pages8
JournalClinical pharmacology and therapeutics
Volume89
Issue number2
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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