Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates
Introduction
One of the most vulnerable processes in fetal life is the development of the brain. During the initial stages of brain development, up to 20 weeks of gestation, neurons proliferate and migrate. In the last trimester of fetal life brain maturation is more refined with processes such as white matter myelinization, glial cell migration and cortical folding [1]. Even after birth, brain maturation is an ongoing process [2], [3]. It is known that different prenatal, perinatal and postnatal events can disturb this process. For instance, it has been shown that twins have a delayed cortical gyrification and that the gyrification of intra-uterine growth restricted newborns is discordant to the normal developmental trajectory with a reduced brain surface compared to normal newborns [4]. Similarly, it has been shown that premature birth has an influence on structural maturation manifested as a decrease in cortical and deep gray matter volume, a smaller cerebral surface area and cerebral volume and a decreased myelinization and gray and white matter differentiation [5], [6], [7]. In addition, neurobehavioural testing has shown a relation between structural deviations and functional maturation at a later time point [4], [5], [7].
Cerebral metabolic rate of glucose (CMRGlc), measured with positron emission tomography (PET), and cerebral blood flow (CBF), measured with xenon-enhanced computed tomography (Xe-CT), are representatives of functional activity and as such brain maturation. These techniques have been used in the past to evaluate brain maturation in infants [8], [9], [10], [11], [12], [13], [14]. At term age functional activity was most prominent in the sensory and motor cortex, the cingulate cortex, the thalamus, the brain stem, the cerebellar vermis and the hippocampal region and it increased in the parietal-, temporal- and visual cortex, the basal ganglia and cerebellar hemispheres by 3 months-equivalent age. Furthermore, associations between local CMRGlc or CBF and outcome have been shown [15], [16], [17]. For instance, moderate CBF values obtained with Xe-CT were related to better outcome than either low or high CBF values [17]. However, major drawbacks such as their invasiveness, the exposure to radiation, the use of radioisotopes and their expense have limited these techniques. A non-invasive tool to assess either the local CMRGlc or CBF might enable us to evaluate brain maturation and to depict abnormal brain development.
In adults, Arterial Spin Labeling (ASL) MR imaging is a well-established technique which enables non-invasive assessment of brain perfusion. Arterial hydrogen protons are inverted in the neck region and a labeled image is acquired after a certain time delay allowing the labeled spins to reach the brain tissue. Control images are acquired as well and when pair-wise subtracting these images a perfusion-weighted image is achieved. In order to increase the signal-to-noise ratio (SNR) this label-control scheme is repeated multiple times resulting in a perfusion map. An earlier study has demonstrated the feasibility of ASL MR imaging to evaluate brain maturation in infants aged 7–13-months old [18]. However, technical difficulties in neonates such as low cerebral blood flow, resulting in lower SNR, and longer tracer lifetime, causing negative perfusion [19], [20], have limited the application of ASL in the younger ‘neonatal’ population. A few studies have described the use of ASL perfusion MR imaging to study brain perfusion in neonates with varying conditions such as asphyxia, stroke and congenital heart defects [20], [21], [22], [23], [24]. A higher perfusion in the brain stem, the thalamus, the basal ganglia and the sensorimotor cortex has been noticed [20], [22] and is in agreement with the earlier described PET studies. However, only perfusion data of infants around term-equivalent age (TEA) have been acquired and a thorough investigation of regional brain perfusion changes with postmenstrual age has not been executed.
The purpose of this research was to evaluate ASL MR imaging as a tool to assess changes in neonatal brain perfusion with age which reflect brain maturation. For this purpose, regional CBF values obtained with ASL MR imaging were evaluated quantitative (ml/100 g min) and relative to the whole brain CBF.
Section snippets
Subjects
Arterial Spin Labeling MR imaging was part of our neonatal imaging protocol. In our institution MR imaging is performed on clinical indication and in infants born before 30 weeks gestational age. In this analysis, 33 subjects were included. Of these 33 infants, Arterial Spin Labeling MR images were evaluated based on image quality which led to the exclusion of 4 infants. As such, data of 29 infants were used for further analysis. Included subjects were infants born before 30 weeks gestational
Results
Arterial Spin Labeling MR images of all included infants were evaluated, 4 of the 33 infants had bad image quality due to motion artifacts (success rate of 87%), data of these infants were excluded from further analysis.
Discussion
The current study shows that ASL perfusion MR imaging can be used to assess brain perfusion in the neonatal population. Results show an increase of wbCBF with age. Furthermore, regional differences in brain perfusion and changes in these differences with age were shown which reflect maturation of the brain.
Previously, regional differences in brain metabolism during brain maturation were shown with PET and Xe-CT [8], [9], [10], [11], [12], [13], [14] and this was shown to reflect regional
Conclusion
In conclusion, regional differences in CBF and changes with postmenstrual age could be detected with ASL in neonates. Our results suggest that ASL may be used as a non-invasive tool to investigate brain maturation in healthy neonates. Future studies should evaluate if ASL can be used to depict abnormal brain development.
Conflict of interest
None declared.
Acknowledgements
This research is supported by the Dutch Technology Foundation STW, applied science division of NOW and the Technology Program of the Ministry of Economic Affairs.
References (30)
- et al.
Myelination progression in language-correlated regions in brain of normal children determined by quantitative MRI assessment
International Journal of Pediatric Otorhinolaryngology
(2008) A critical period of brain development: studies of cerebral glucose utilization with PET
Preventive Medicine
(1998)- et al.
Regional variations in human newborn cerebral blood flow
Journal of Pediatrics
(1988) - et al.
Assessment of functional development in normal infant brain using arterial spin labeled perfusion MRI
Neuroimage
(2008) - et al.
Noninvasive cerebral perfusion imaging in high-risk neonates
Seminars in Perinatology
(2010) - et al.
Why perfusion in neonates with congenital heart defects is negative--technical issues related to pulsed arterial spin labeling
Magnetic Resonance Imaging
(2006) - et al.
Preoperative cerebral blood flow is diminished in neonates with severe congenital heart defects
Journal of Thoracic and Cardiovascular Surgery
(2004) - et al.
Cerebral maturation in premature infants: quantitative assessment using MR imaging
American Journal of Neuroradiology
(2001) - et al.
Diffusion tensor imaging assessment of brain white matter maturation during the first postnatal year
American Journal of Roentgenology
(2007) - et al.
Primary cortical folding in the human newborn: an early marker of later functional development
Brain
(2008)
Structural and neurobehavioral delay in postnatal brain development of preterm infants
Pediatric Research
Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth
PLoS Med
Abnormal cerebral structure is present at term in premature infants
Pediatrics
Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography
Science
Positron emission tomography study of human brain functional development
Annals of Neurology
Cited by (54)
Brain perfusion imaging in neonates
2021, NeuroImage: ClinicalArterial spin labeling perfusion in neonates
2020, Seminars in Fetal and Neonatal MedicineDevelopment of Brain Networks In Utero: Relevance for Common Neural Disorders
2020, Biological PsychiatryArterial spin-labeling magnetic resonance imaging of brain maturation in early childhood: Mathematical model fitting to assess age-dependent change of cerebral blood flow
2019, Magnetic Resonance ImagingCitation Excerpt :Furthermore, the vascularized basal ganglia may be subject to variable contribution of the vascular signal during perfusion measurement [11], reducing the reliability of CBF measurement using ASL imaging. Unlike the neonatal study reported by De Vis et al. [11], our study investigated a population comprising neonates, infants, and young children, the trajectory results were based on mathematical fitting of the data obtained from all patients and not only from the neonates. Moreover, only common models were selected to fit the CBF measurements in our study, a more complicated model that better fit the measurements may exist that was not selected for our analysis.
- 1
Department of Radiology, University Medical Center Utrecht Postbus 85500, Hp E.01.132 3508 GA Utrecht, The Netherlands. Tel.: +3188 7556687.
- 2
Department of Neonatology, University Medical Center Utrecht Postbus 85090, KE 04.1231 3508 GA Utrecht, The Netherlands. Tel.: +3188 7554545.
- 3
Department of Neonatology, University Medical Center Utrecht Postbus 85090, KE 04.1231 3508 GA Utrecht, The Netherlands. Tel.: +3188 7554545.
- 4
Department of Neonatology, University Medical Center Utrecht Postbus 85090, KE 04.1231 3508 GA Utrecht, The Netherlands. Tel.: +3188 7554545.
- 5
Department of Neonatology, University Medical Center Utrecht Postbus 85090, KE 04.1231 3508 GA Utrecht, The Netherlands. Tel.: +3188 7554545.
- 6
Department of Radiology, University Medical Center Utrecht Postbus 85500, Hp E.01.132. 3508 GA Utrecht, The Netherlands. Tel: +3188 7556687.
- 7
Department of Neonatology, University Medical Center Utrecht Postbus 85090, KE 04.1231 3508 GA Utrecht, The Netherlands. Tel.: +3188 7554545.