title: Altered resting cerebral blood flow in adolescents with in utero cocaine exposure revealed by perfusion functional MRI.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Radiology and Neurology, Center for Functional Neuroimaging, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Hengyi
authors.initials: H
authors.lastname: Rao
authors.forename: Jiongjiong
authors.initials: J
authors.lastname: Wang
authors.forename: Joan
authors.initials: J
authors.lastname: Giannetta
authors.forename: Marc
authors.initials: M
authors.lastname: Korczykowski
authors.forename: David
authors.initials: D
authors.lastname: Shera
authors.forename: Brian B
authors.initials: BB
authors.lastname: Avants
authors.forename: James
authors.initials: J
authors.lastname: Gee
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.forename: Hallam
authors.initials: H
authors.lastname: Hurt
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001776:Blood Circulation Time / Q000379:methods; D001783:Blood Flow Velocity; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012146:Rest / Q000502:physiology*
chemical_list: D003042:Cocaine