Differential responses in CBF and CBV to cocaine as measured by fMRI: Implications for pharmacological MRI signals derived oxygen metabolism assessment

Abstract

Introduction Cognitive performance-induced brain oxygen metabolism has been successfully measured by functional magnetic resonance imaging (fMRI) in human studies. The measurement of the cerebral metabolic rate of oxygen consumption (CMRO 2) is typically achieved by assuming a fixed coupling of cerebral blood flow (CBF) and cerebral blood volume (CBV) and by performing a separate experiment to assess the vascular response to a hypercapnic challenge. Psychoactive drugs may have directly effect on the cerebral vasculature, potentially confounding the interpretation of pharmacological MRI (phMRI) data. In this study, we tested the assumptions of the standard CMRO 2 calculation following the administration of cocaine, in order to test the validity of this measurement in phMRI studies. The initial transient state and later steady state CBF and CBV responses to a hypercapnic challenge were measured. Methods CBF and CBV responses were directly measured by fMRI using continuous arterial spin-labeling (ASL) and contrast-enhanced fMRI, respectively. The coupling between changes in CBF and CBV during a hypercapnic challenge was examined under normal conditions and following the administration of cocaine. Results A decoupling of changes in CBF and CBV was observed during the transient state immediately following the administration of cocaine, and an altered coupling of CBF and CBV was found during the steady state after cocaine injection. Discussion These data suggest caution in interpreting CMRO 2 measurements from phMRI studies and may also lead to an improved understanding of the complex neuronal and vascular mechanisms of drug action.