Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury

Mahdi, Eman; Bouyssi-Kobar, Marine; Jacobs, Marni; Murnick, Jonathan; Chang, Taeun; Limperopoulos, Catherine

doi:10.3174/ajnr.a5669

Cited by 11 publications

(9 citation statements)

References 41 publications

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“…Measurement of exact arterial transit delay in newborns may be warranted in future studies to confirm optimal postlabeling delay. Our quantified global CBF measurements in preterm infants are largely in agreement with previous preterm ASL studies (6)(7)(8)(9)(12)(13)(14)(15). Our measurements are most comparable to those in the studies by De Vis et al (7)(8)(9), in which T1 b was measured in each infant, similar to our study.…”

Section: Discussionsupporting

confidence: 92%

“…We report a significant association between CBF and IVH in preterm infants. Previous studies also demonstrated associations between brain injury and low ASL CBF (12)(13)(14) or low oxygen delivery based on results of near-infrared spectroscopy (32,33). Particularly, one study showed that oxygen delivery in the preterm brain was associated with IVH but not parenchymal injury (32).…”

Section: Discussionmentioning

confidence: 97%

“…Second, T1 b needs to be measured in each infant for accurate quantification because T1 b of newborns is different from that of adults and because there is a wide variation across different infants and different ages (19). Last, while many preterm ASL studies used small regions of interest drawn manually on a few slices (6,7,11,(13)(14)(15), larger regions of interest may be desirable for increased confidence in ASL measurements through massive signal averaging within each region (26). In this study, we addressed these obstacles to acquire reliable measurements of regional CBF in newborn infants.…”

Section: Discussionmentioning

confidence: 99%

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

Zun¹,

Kapse²,

Jacobs³

et al. 2021

Radiology

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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...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Zun¹,

Kapse²,

Jacobs³

et al. 2021

Radiology

Self Cite

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“…However, studies beyond early adulthood are limited, with most studies employing a single method approach. Further, to our knowledge, GM perfusion has not been examined in this population beyond infancy despite preliminary data showing that preterm birth may be associated with both increased and decreased cerebral perfusion (Mahdi et al, 2018). Perfusion dysfunction may be associated with structural alterations, and has even been shown to precede structural loss in some scenarios (Chételat et al, 2007; Gonzalez-Redondo et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Altered grey matter volume, perfusion and white matter integrity in very low birthweight adults

Pascoe

Melzer

Horwood

et al. 2019

NeuroImage: Clinical

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This study examined the long-term effects of being born very-low-birth-weight (VLBW, <1500 g) on adult cerebral structural development using a multi-method neuroimaging approach. The New Zealand VLBW study cohort comprised 413 individuals born VLBW in 1986. Of the 338 who survived to discharge, 229 were assessed at age 27–29 years. Of these, 150 had a 3 T MRI scan alongside 50 healthy term-born controls. The VLBW group included 53/57 participants born <28 weeks gestation. MRI analyses included: a) structural MRI to assess grey matter (GM) volume and cortical thickness; b) arterial spin labelling (ASL) to quantify GM perfusion; and c) diffusion tensor imaging (DTI) to measure white matter (WM) integrity. Compared to controls, VLBW adults had smaller GM volumes within frontal, temporal, parietal and occipital cortices, bilateral cingulate gyri and left caudate, as well as greater GM volumes in frontal, temporal and occipital areas. Thinner cortex was observed within frontal, temporal and parietal cortices. VLBW adults also had less GM perfusion within limited temporal areas, bilateral hippocampi and thalami. Finally, lower fractional anisotropy (FA) and axial diffusivity (AD) within principal WM tracts was observed in VLBW subjects. Within the VLBW group, birthweight was positively correlated with GM volume and perfusion in cortical and subcortical regions, as well as FA and AD across numerous principal WM tracts. Between group differences within temporal cortices were evident across all imaging modalities, suggesting that the temporal lobe may be particularly susceptible to disruption in development following preterm birth. Overall, findings reveal enduring and pervasive effects of preterm birth on brain structural development, with individuals born at lower birthweights having greater long-term neuropathology.

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“…The results of this study showed that compared with healthy mice, the apoptosis of hippocampal CA1 and cortical neurons in the brain injury model of preterm mice increased significantly, and the level of Bax protein increased significantly and the level of Bcl-2 protein decreased significantly. It shows that obvious damage occurred in the brain tissue of preterm mice [ 25 ]. EPO can reduce neuronal apoptosis and increase the ratio of Bcl-2/Bax in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of erythropoietin-induced M2 microglia polarization via Akt / Mtor / P70S6k signaling pathway in the treatment of brain injury in premature mice and its effect on biofilm

Wang

et al. 2022

Bioengineered

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We investigated the mechanism of erythropoietin (EPO) in brain injury in premature mice based on Akt/mTOR/p70S6K signaling pathway. The brain injury model group of premature mice was obtained by intraperitoneal injection of lipopolysaccharide during pregnancy. Normal mice were taken as the control group. The model mice were divided into low-dose EPO (1,000 IU/kg, L-EPO), medium-dose EPO (2,500 IU/kg, M-EPO), and high-dose EPO groups (5,000 IU/kg, H-EPO) by intraperitoneal injection. The levels of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were detected. TUNEL staining and Western blotting were used to detect the differences in neuronal apoptosis index (AI), microglial polarization marker protein, and Akt/mTOR/p70S6K-related protein expression levels in each group. Compared with the control group, the protein levels of AI, MDA, Bax, and iNOS in the model, L-EPO, and M-EPO groups were significantly increased, while the T-SOD level and Bcl-2, ARG1, p-Akt, p-mTOR, and p-70S6K protein levels were significantly decreased ( P < 0.05). Compared with the model group, AI, MAD levels and Bax, iNOS protein expression levels in L-EPO, M-EPO, and H-EPO groups were significantly decreased, while T-SOD level and Bcl-2, ARG1, p-Akt, p-mTOR, and p-70S6K protein levels were significantly increased. The changes were dose-dependent. In summary, EPO can activate microglia transformation from M1 to M2 through Akt/mTOR/p70S6K signaling pathway.

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Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury

Abstract: We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry.

Cited by 11 publications

References 41 publications

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

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

Altered grey matter volume, perfusion and white matter integrity in very low birthweight adults

Mechanism of erythropoietin-induced M2 microglia polarization via Akt / Mtor / P70S6k signaling pathway in the treatment of brain injury in premature mice and its effect on biofilm

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