Brain injury is a frequent complication in newborns with complex congenital heart disease (CHD) secondary to hemodynamic instability and increased risk for hypoxic-ischemic injury. In this study quantitative susceptibility mapping (QSM) was performed in newborns with complex CHD prior to open heart surgery and was compared to healthy control newborns. Mean susceptibility was significantly higher in the cortical gray matter of neonates with CHD versus controls suggesting reduced oxygenation in the cerebral vasculature in CHD preoperatively. QSM images also depicted less contrast in the CHD, which may be associated with delayed brain development. This is the first report to demonstrate the feasibility of neonatal QSM and susceptibility differences between CHD and controls.
METHODS
Five neonates diagnosed with CHD and 14 healthy control neonates were recruited in the context of a separate prospective study. MR phase imaging was performed using a 3D multi-echo flow-compensated gradient echo sequence with imaging parameters of TR = 55 ms, TE = 5.8, 12.2, 18.6, 25.0, 31.4, 37.8, 44.2 ms, BW = 50 kHz, flip-angle = 20°, FOV = 16 cm, and spatial revolution of 0.38 x 0.5 x 2 mm3. Total scan time was 6:09 min with parallel imaging (acceleration factor=2). All MRI scans were performed on a GE MR 750 3T scanner using an 8-channel head coil while the infants were breathing room air. QSM reconstruction was performed using the approach of morphology-enabled dipole inversion (MEDI)7. Estimated susceptibility maps were registered to T2-weighted images of the same subject using rigid-body image registration with SPM (Wellcome Trust Center for NeuroImaging, UCL, UK) and then registered to the templates of the neonatal brain using nonrigid-body registration with ANTS (http://stnava.github.io/ANTs). Brain regions were segmented using the Draw-EM neonatal atlas (https://github.com/MIRTK/DrawEM). All other analysis was performed using Matlab (MathWorks, Natick, MA).RESULTS
One neonate with CHD and 1 healthy neonate were excluded from the analysis due to image artifacts caused by subject motion during MR image acquisition. Data from the remaining 4 neonates with CHD and 13 healthy neonates were used for QSM analysis. Mean age at the time of MRI scan was 7±12 days for CHD and 14±8 days for healthy neonates (p=0.11). Cardiac diagnoses included ventricular septal defect, hypoplastic left heart syndrome, d-transposition of the great arteries, and truncus arteriosus. Measured mean susceptibility was 40±13 vs 20±14 in the cortical gray matter, 12±30 vs 11±17 in the white matter, and -61±38 vs -38±40 in the deep gray matter for CHD vs healthy controls, respectively (all in unit of 10-4 ppm). Figure 1 shows the box and whisker plot of measured susceptibility in the three regions. Among those regions, only cortical gray matter showed a significant difference in susceptibility between CHD and controls when controlling for age (p=0.02). Figure 2 shows QSM images of representative infants (one CHD and one control) and demonstrates increased cortical gray matter susceptibility in the infant diagnosed with CHD. In addition, the healthy infant showed greater spatially variant contrast representing more developed brain structure than the infant with CHD. Unlike adult brain, the neonatal brains showed no hyperintensity in the basal ganglia on QSM images due to insufficient iron deposition.1. Licht DJ, Wang J, Silvestre DW, et al. Preoperative cerebral blood flow is diminished in neonates with severe congenital heart defects. J Thorac Cardiovasc Surg. 2004;128:841-849.
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