Introduction

Neonatal hyperbilirubinemia (NHB) is a common clinical problem in the neonatal period, especially in the first week after birth1. Severe NHB (4.8%) can lead to bilirubin encephalopathy (BE), in which 50% to 70% of severe BE patients die in the acute phase, while 75% to 90% of survivors can have severe neurological sequelae such as cerebral palsy, audiovisual impairment, and intellectual impairment2. In previous studies on NHB, it was believed that the high signal of T1 in globus pallidus (GP) can be used as an objective indicator to evaluate NHB and BE3, but it is prone to change due to different imaging techniques, and it is more likely to present high signal in high field intensity and 3D sequence4. Therefore, it is still necessary to find a method that can correctly quantify the signal strength of GP. T1 mapping technology can directly measure the T1 value of tissues and reflect the water content of cells5. This study aims to use T1 mapping imaging to measure the T1 value of each brain area of neonates with NHB, quantify the degree of brain injury accurately, and observe the change trend of T1 value with serum Total Bilirubin (TBil), and provide objective imaging basis for clinical.

Material and Methods

Our Institutional Review Board approved the protocol and written informed consent was obtained from guardians of each neonate. 40 neonates with hyperbilirubinemia (H group, average TBil 250.617±41.574μmol/L) and 26 neonates with encephalopathy (E group, average TBil 391.146±84.791μmol/L) were retrospectively analyzed, and 27 neonates with physiologic jaundice (C group, average TBil 150.089±70.917μmol/L) were selected as control group. All newborns were examined on a 3.0T MR scanner (MR750W; GE Healthcare, Milwaukee, USA) equipped with a 12-channel head coil. The scan sequences include routine axial(AX) T1-weighted imaging, T2-weighted imaging and T1 mapping. The T1 mapping parameters were as follows: TR=3500ms, TE=25.2ms, Bandwidth=62.5kHz, phase encoding FOV=1, frequency coding FOV=22, matrix=128x128, slice thickness/gap=4/0 mm, six different reversal times (TI), respectively 200ms, 400ms, 600ms, 800ms, 1000ms, 1200ms, and scanning time=7min6s. The raw data were imported into the post-processing software FuncTool to generate T1 maps. The six pairs of brain regions, namely bilateral GP, PU, caudate nucleus head (CA), dorsal thalamus (TH), anterior limb of internal capsule (ALIC) and PLIC, were measured. The ROI was manually set at the maximum level of each brain region. The mean value of T1 was obtained by measuring the same part three times, and the T1 value of each ROI was recorded. One-way analysis of variance was used to compare T1 values in each brain area among the three groups. If there were differences, LSD-T test was used for pairwise comparison. Correlation analysis between TBil and T1 value of each brain region was conducted by Pearson correlation.

Results

The results of statistical analysis showed that T1 values in each brain area were arranged from large to small as C group, H group and E group (Table 1, Figure 1). T1 values of GP and PLIC were significantly different among all groups (F=5.979 and F=6.943, respectively, P < 0.05) (Table 1). T1 values of GP and PLIC were significantly different between C group and E group (P=0.002, P=0.008) and between H group and E group (P=0.023, P=0.028) (Table 2). Linear correlation analysis showed that T1 values of GP, PU and PLIC were negatively correlated with TBil (r values were -0.338, -0.414 and -0.352, respectively, P < 0.05) (Table 3).

Discussion and Conclusion

In this study, T1 mapping can reflect the changes of T1 values in various brain regions of neonates with hyperbilirubinemia, suggesting the damage of different brain regions by bilirubin and the possibility of corresponding neurological function changes. T1 values of GP, PU and PLIC were negatively correlated with bilirubin values, suggesting that these brain regions were significantly affected by bilirubin. GP is related to muscle tension and postural reflex of limbs. PU participates in the regulation of learning and movement. Internal capsule (IC) is an important structure in the cerebral hemisphere. It contains a large number of fasciculus, in which the corticospinal tract, optic radiation and auditory radiation pass through the PLIC6. Our findings suggest that bilirubin may have shortened the longitudinal relaxation time of GP, PU and PLIC, and potentially weakened the function of corresponding brain regions, which was consistent with the neurological dysfunction induced by bilirubin. But it's not clear why bilirubin lowers T1 in these brain regions. Bin-nun et al.7 believed that bilirubin could damage nerve cell membranes and cause calcium to deposit in damaged neurons, thus shortening T1 relaxation time. But Hansen T et al.8 recognized that when neurons and glial cells were damaged by bilirubin, nerve fibers could be dys-myelinated to a certain extent or the phospholipin of myelin was destroyed or lost, which reduced the macromolecules in these brain regions, thus decreasing the T1 value. The major limitations of our study were the relatively small number of cases and the lack of comparison with other neonatal encephalopathy to highlight its specificity. Thus, multi-center and large sample size research is still needed. To conclude, T1 mapping could be used to evaluate brain injury in neonates with NHB quantificationally.

Acknowledgements

We acknowledge Dr. Xiaocheng Wei from MR Research, GE Healthcare for technical support on T1 mapping sequence as well as helpful discussions.