Changes in brain perfusion in successive arterial spin labeling MRI scans in neonates with hypoxic-ischemic encephalopathy

Abstract

The primary objective of this study was to evaluate changes in cerebral blood flow (CBF) using arterial spin labeling MRI between day 4 of life (DOL4) and day 11 of life (DOL11) in neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. The secondary objectives were to compare CBF values between the different regions of interest (ROIs) and between infants with ischemic lesions on MRI and infants with normal MRI findings. We prospectively included all consecutive neonates with HIE admitted to the neonatal intensive care unit of our institution who were eligible for therapeutic hypothermia. Each neonate systematically underwent two MRI examinations as close as possible to day 4 (early MRI) and day 11 (late MRI) of life. A custom processing pipeline of morphological and perfusion imaging data adapted to neonates was developed to perform automated ROI analysis. Twenty-eight neonates were included in the study between April 2015 and December 2017. There were 16 boys and 12 girls. Statistical analysis was finally performed on 37 MRIs, 17 early MRIs and 20 late MRIs. Eleven neonates had both early and late MRIs of good quality available. Eight out of 17 neonates (47%) had an abnormal on late MRI as performed and 7/20 neonates (35%) had an abnormal late MRI. CBF values in the basal ganglia and thalami (BGT) and temporal lobes were significantly higher on DOL4 than on DOL11. There were no significant differences between DOL4 and DOL11 for the other ROIs. CBF values were significantly higher in the BGT vs. the cortical GM, on both DOL4 and DOL11. On DOL4, the CBF was significantly higher in the cortical GM, the BGT, and the frontal and parietal lobes in subjects with an abnormal MRI compared to those with a normal MRI. On DOL11, CBF values in each ROI were not significantly different between the normal MRI group and the abnormal MRI group, except for the temporal lobes. This article proposes an innovative processing pipeline for morphological and ASL data suited to neonates that enable automated segmentation to obtain CBF values over ROIs. We evaluate CBF on two successive scans within the first 15 days of life in the same subjects. ASL imaging in asphyxiated neonates seems more relevant when used relatively early, in the first days of life. The correlation of intra-subject changes in cerebral perfusion between early and late MRI with neurodevelopmental outcome warrants investigation in a larger cohort, to determine whether the CBF pattern change can provide prognostic information beyond that provided by visible structural abnormalities on conventional MRI.

Keywords: ASL; Asphyxia; Cerebral perfusion; MRI; Neonates.

Fig. 1

Overview of our processing pipeline illustrated in one subject, at day of life 4 (DOL4). The transformations T_R, T_O and T_C resulting from the different registration steps are indicated in diamonds. The circle symbol represents the composition of transformations.

Fig. 2

Steps of the construction of our custom atlas from ALBERTs data (20 neonate subjects along with 50 manually drawn ROIs). Our custom atlas results in an average T1w image with associated ROIs, as well as an extracted average brain and a binary brain mask.

Fig. 3

Processing steps for brain extraction. The transformations T_S, T_A and T_M resulting from the different registration steps are indicated in diamonds. The circle symbol represents the composition of transformations.

Fig. 4

Axial images of an ASL perfusion map (A) and ROI as overlay (B) with frontal (blue), parietal (dark green), occipital (pink) and temporal (purple) lobes, and basal ganglia and thalami (light green).

Fig. 5

Changes in cerebral blood flow in the basal ganglia and thalami for each subject (paired sample, n = 11) between day 4 and day 11 of life. The box-and-whisker plots show the lower and upper quartiles (box edges), medians (line in boxes) and minimum/maximum values (lines at ends of whiskers). The dot-and-line diagrams show infants with injury (n = 5) (red squares and lines) and without injury (n = 6) (green circles and lines) on MRI. Differences between DOL4 and DOL11 were significant (p = .049). BGT = Basal Ganglia and Thalami; CBF = Cerebral Blood Flow; DOL4 = day 4 of life, DOL11 = day 11 of life.

Fig. 6

Cerebral blood flow in ROIs on day 4 of life (n = 17) and day 11 of life (n = 20). Box-and-whisker plots show the lower to upper quartiles (box edges), medians (line in boxes) and minimum/maximum values (lines at ends of whiskers). The mark represents the mean. The dot-and-line diagrams (in blue) show infants with both early and late MRI (n = 11). The asterisk represents significant difference [p < .05] [Wilcoxon test for paired samples]. Differences between cortical GM and BGT were significant on both early and late MRI. Difference between frontal and temporal lobes was significant on early MRI. BGT = Basal Ganglia and Thalami; CBF = Cerebral Blood Flow; DOL4 = day 4 of life; DOL11 = day 11 of life; Cortical GM = Grey matter in lobes; ROI = Region Of Interest.

Fig. 7

Cerebral blood flow in brain, grey matter in lobes, and basal ganglia and thalami on day 4 of life for subjects with normal MRI (n = 9) vs. abnormal MRI (n = 8) and on day 11 of life for subjects with normal MRI (n = 13) vs. abnormal MRI (n = 7). Box-and-whisker plots show the lower and upper quartiles (box edges), medians (line in boxes) and minimum/maximum values (lines at ends of whiskers). Differences between infants with vs. without injury on MRI were significant (asterisk) on DOL 4 in the BGT (p = .0269) and in the cortical GM (p = .0433) [Mann-Whitney test for independent samples]. A = Abnormal MRI; BGT = Basal Ganglia and Thalami; CBF = Cerebral Blood Flow; DOL4 = day 4 of life; DOL11 = day 11 of life; Cortical GM = Grey matter in lobes; N = Normal MRI; ROI = Region Of Interest.