title: Heterogeneous increases of regional cerebral blood flow during preterm brain development: Preliminary assessment with pseudo-continuous arterial spin labeled perfusion MRI.
abstract: The human brain develops rapidly during 32-45 postmenstrual weeks (PMW), a critical stage characterized by dramatic increases of metabolic demand. The increasing metabolic demand can be inferred through measurements of regional cerebral blood flow (CBF), which might be coupled to regional metabolism in preterm brains. Arterial spin labeled (ASL) perfusion MRI is one of the few viable approaches for imaging regional CBF of preterm brains, but must be optimized for the extremely slow blood velocity unique in preterm brains. In this study, we explored the spatiotemporal CBF distribution in newborns scanned at the age of 32-45PMW using a pseudo-continuous ASL (pCASL) protocol adapted to slow blood flow in neonates. A total of 89 neonates were recruited. PCASL MRI was acquired from 34 normal newborns and phase contrast (PC) images from 19 newborns. Diffusion tensor images (DTI) were acquired from all 89 neonates for measuring cortical fractional anisotropy (FA), which characterizes cortical microstructure. Reproducible CBF measurements were obtained with the adjusted pCASL sequence. Global CBF measurement based on PC MRI was found to double its value in the 3rd trimester. Regional CBF increases were heterogeneous across the brain with a significantly higher rate of CBF increase in the frontal lobe and a lower rate of CBF increase in the occipital lobe. A significant correlation was found between frontal cortical CBF and cortical FA measurements (p<0.01). Increasing CBF values observed in the frontal lobe corresponded to lower FA values, suggesting that dendritic arborization and synaptic formation might be associated with an elevated local CBF. These results offer a preliminary account of heterogeneous regional CBF increases in a vital early developmental period and may shed the light on underlying metabolic support for cortical microstructural changes during the developmental period of 32-45PMW. Preterm effects and limitations of pCASL techniques in newborns need to be carefully considered for interpretation these results.
authors.affiliation: Radiology Research, Children's Hospital of Philadelphia, PA, United States; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, TX, United States; Biomedical Engineering Joint Graduate Program, University of Texas at Arlington-University of Texas Southwestern Medical Center, TX, United States.
authors.forename: Minhui
authors.initials: M
authors.lastname: Ouyang
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, TX, United States; Department of Radiology, School of Medicine, Johns Hopkins University, MD, United States.
authors.forename: Peiying
authors.initials: P
authors.lastname: Liu
authors.affiliation: Radiology Research, Children's Hospital of Philadelphia, PA, United States; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, TX, United States; Biomedical Engineering Joint Graduate Program, University of Texas at Arlington-University of Texas Southwestern Medical Center, TX, United States.
authors.forename: Tina
authors.initials: T
authors.lastname: Jeon
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Lina
authors.initials: L
authors.lastname: Chalak
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Roy
authors.initials: R
authors.lastname: Heyne
authors.affiliation: Departemnt of Radiology, Children's Medical Center, Dallas, TX, United States.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Rollins
authors.affiliation: Division of Neurology, Children's Hospital of Philadelphia, PA, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Licht
authors.affiliation: Department of Neurology, University of Pennsylvania, PA, United States; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, PA, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.affiliation: Radiology Research, Children's Hospital of Philadelphia, PA, United States; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, PA, United States.
authors.forename: Timothy P L
authors.initials: TPL
authors.lastname: Roberts
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, TX, United States; Department of Radiology, School of Medicine, Johns Hopkins University, MD, United States.
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Lu
authors.affiliation: Radiology Research, Children's Hospital of Philadelphia, PA, United States; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, TX, United States; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, PA, United States. Electronic address: huangh6@email.chop.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
mesh_terms: D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D013113:Spin Labels
chemical_list: D013113:Spin Labels
keywords: Arterial spin labeled; Brain development; Cerebral blood flow; Cortical microstructure; Heterogeneous; Preterm brain