Published online November 1, 2007
PEDIATRICS Vol. 120 No. 5 November 2007, pp. e1245-e1254 (doi:10.1542/peds.2006-2596)
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ARTICLE

Altered Resting Cerebral Blood Flow in Adolescents With in Utero Cocaine Exposure Revealed by Perfusion Functional MRI

Hengyi Rao, PhDa, Jiongjiong Wang, PhDa, Joan Giannetta, BAb, Marc Korczykowski, MSa, David Shera, ScDc, Brian B. Avants, PhDa, James Gee, PhDa, John A. Detre, MDa and Hallam Hurt, MDb

a Department of Radiology and Neurology, Center for Functional Neuroimaging, University of Pennsylvania, Philadelphia, Pennsylvania
b Divisions of Neonatology
c Biostatistics and Epidemiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

OBJECTIVES. Animal studies have clearly demonstrated the effects of in utero cocaine exposure on neural ontogeny, especially in dopamine-rich areas of cerebral cortex; however, less is known about how in utero cocaine exposure affects longitudinal neurocognitive development of the human brain. We used continuous arterial spin-labeling perfusion functional MRI to measure the effect of in utero cocaine exposure on resting brain function by comparing resting cerebral blood flow of cocaine-exposed adolescents with non–cocaine-exposed control subjects.

PATIENTS AND METHODS. Twenty-four cocaine-exposed adolescents and 25 matched non–cocaine-exposed control subjects underwent structural and perfusion functional MRI during resting states. Direct subtraction, voxel-wise general linear modeling, and region-of-interest analyses were performed on the cerebral blood flow images to compare the resting cerebral blood flow between the 2 groups.

RESULTS. Compared with control subjects, cocaine-exposed adolescents showed significantly reduced global cerebral blood flow. The decrease of cerebral blood flow in cocaine-exposed adolescents was observed mainly in posterior and inferior brain regions, including the occipital cortex and thalamus. After adjusting for global cerebral blood flow, however, a significant increase in relative cerebral blood flow in cocaine-exposed adolescents was found in anterior and superior brain regions, including the prefrontal, cingulate, insular, amygdala, and superior parietal cortex. Furthermore, the functional modulations by in utero cocaine exposure on all of these regions except amygdala cannot be accounted for by the variation in brain anatomy.

CONCLUSIONS. In utero cocaine exposure may reduce global cerebral blood flow, and this reduction may persist into adolescence. The relative increase of cerebral blood flow in anterior and superior brain regions in cocaine-exposed adolescent participants suggests that compensatory mechanisms for reduced global cerebral blood flow may develop during neural ontogeny. Arterial spin-labeling perfusion MRI may be a valuable tool for investigating the long-term effects of in utero drug exposure.

Key Words: in utero cocaine exposure • ASL perfusion fMRI • cerebral blood flow • frontal lobe • adolescence

Abbreviations: IUCE—in-utero cocaine exposure • ASL—arterial spin labeling • fMRI—functional MRI • CBF—cerebral blood flow • BOLD—blood oxygen-dependent level • ROI—region of interest • VBM—voxel-based morphometry • COC—cocaine-exposed adolescent • CON—non–cocaine-exposed control • TR—repetition time • FDR—false-discovery rate

Accepted Apr 19, 2007.