Longitudinal Trajectories of Regional Cerebral Blood Flow in Very Preterm Infants during Third Trimester Ex Utero Development Assessed with MRI

Abstract

N eurodevelopmental disabilities after premature exposure to extrauterine life remain prevalent and manifold and include motor, cognitive, behavioral, and socioaffective impairments (1). Notably, these neurodevelopmental impairments often take years to manifest, and early biomarkers of risk are needed to guide medical and rehabilitative interventions that mitigate risk.Coincident with premature extrauterine exposure are critical periods of brain development that may place the preterm infant at risk for impaired brain development. Third trimester brain development is particularly accelerated (2,3), presumably because of energy-dependent processes that demand an increasing supply of blood-borne oxygen and nutrients to the brain. Until recently, our ability to safely measure and monitor the developmental trajectories of regional cerebral blood flow (CBF) in the ex utero preterm infant over the third trimester of development was limited.Arterial spin labeling (ASL) has emerged as a powerful MRI tool to use in the quantitative measurement of regional CBF, as there is no contrast agent or exposure to ionizing radiation (4,5). Several prior studies have used ASL to study CBF in preterm infants, but ASL has largely been used at term-equivalent age (TEA) or in studies with a cross-sectional design (6-15). Longitudinal noninvasive assessment of CBF in different regions of the immature brain during the ex utero third trimester will allow better understanding of the role of premature exposure to the extrauterine milieu and its association with brain injury and clinical risk factors. Background:The third trimester of gestation is a crucial phase of rapid brain development, but little has been reported on the trajectories of cerebral blood flow (CBF) in preterm infants in this period.Purpose: To quantify regional CBF in very preterm infants longitudinally across the ex utero third trimester and to determine its relationship with clinical factors associated with brain injury and premature birth. Materials and Methods:In this prospective study, very preterm infants were enrolled for three longitudinal MRI scans, and 22 healthy full-term infants were enrolled for one term MRI scan between November 2016 and February 2019. Global and regional CBF in the cortical gray matter, white matter, deep gray matter, and cerebellum were measured using arterial spin labeling with postlabeling delay of 2025 msec at 1.5 T and 3.0 T. Brain injury and clinical risk factors in preterm infants were investigated to determine associations with CBF. Generalized estimating equations were used to account for correlations between repeated measures in the same individual.Results: A total of 75 preterm infants (mean postmenstrual age [PMA]: 29.5 weeks  2.3 [standard deviation], 34.9 weeks  0.8, and 39.3 weeks  2.0 for each scan; 43 male infants) and 22 full-term infants (mean PMA, 42.1 weeks  2.0; 13 male infants) were evaluated. In preterm infants, global CBF was 11.9 mL/100 g/min  0.2 (standard error). All regional CBF increased significantly with ad...

Association of Cerebral Blood Flow and Brain Tissue Relaxation Time With Neurodevelopmental Outcomes of Preterm Neonates

“…6,19 By using multidelay ASL with longer postlabeling delays, we were able to overcome the slow CBF of neonates that would normally affect CBF estimations. In addition, we reconstructed the tCBF maps with multiple postlabeling delays, and during this process, we adjusted the T1 relaxation times for blood and tissue in neonates 6,7 because these values would differ between neonates and adults. T1 blood relaxation times were adjusted according to the hematocrit level of each neonate, and T1 tissue relaxation times for WM were adjusted according to the values obtained from synthetic MRI.…”

“…Although preterm neonates at termequivalent age would generally show less brain maturation compared with term neonates, 9,33 several studies have shown faster maturation in preterm neonates for specific brain regions. 7,9,33,34 Likewise, when a semiquantitative scoring system was applied, preterm neonates showed a higher degree of maturation in frontal and occipital WM compared with term neonates. 33 This advanced maturation in preterm neonates has been interpreted as a result of early exposure to the extrauterine environment.…”

“…According to our results, we can postulate that higher CBF in frontal WM reflects abnormally accelerated brain maturation that has been affected by preterm birth. Although preterm neonates at term-equivalent age would generally show less brain maturation compared with term neonates, 9,33 several studies have shown faster maturation in preterm neonates for specific brain regions 7,9,33,34 . Likewise, when a semiquantitative scoring system was applied, preterm neonates showed a higher degree of maturation in frontal and occipital WM compared with term neonates 33 .…”

“…Studies have shown that regional CBF measured with ASL can be used to quantify brain maturation in neonates. [5][6][7] Compared with older children, neonates have lower CBF, lower blood flow velocity, smaller brain size, and different relaxation times for blood and brain tissue that make it harder to apply ASL. With multidelay ASL using the Hadamard encoding method, 8 however, it has been possible to obtain transit timecorrected CBF (tCBF) maps within reasonable scanning times in neonates.…”

Change and clinical significance of serum cortisol, BNP, and PGE-2 levels in premature infants with patent ductus arteriosus

“…However, the influence mechanism of cortisol on the closure of the arterial catheter is unclear (17). Animal experiments have shown that cortisol can reduce prostaglandin synthesis by inhibiting phospholipase A, and can reduce the sensitivity of the arterial catheter to the prostaglandin expansion effect (18,19). Studies have also found that cortisol itself has a weak contractile effect on the artery (20).…”