During the brain development of premature infants, DKI can reveal the microstructure changes and maturation processes in different brain regions. Through comparison with term infants, our research shows that DKI can effectively diagnose delayed brain development in premature infants. Compared with the parameter FA, the parameters MK and RK of DKI can better capture microstructure changes. When describing gray matter structure, such as TH and CN, MK is better than FA. These results indicate that MK is superior to FA in diagnosing premature infants with delayed brain development. It is more advantageous in discovering changes in the microstructure of the brain.
Because premature birth may lead to relatively slow brain development in premature infants, there are some brain regions that are less developed than full-term infants. In this study we found that the MK and RK values of PLIC and ALIC were lower than those of the full-term infants. The fibers that made up the internal capsule (IC) came from the descending fibers of the cerebral cortex. The following factors affected the development of the complex structure of IC [12, 13], i.e. the increase of nerve cell axon diameter, change of nerve cell membrane composition, myelination of axons continued to improve, increase in the number of microglia, and decreased extracellular space. The parameters of DKI, such as MK, RK can sensitively reflect these microstructure complexity. This is also in line with Paydar’s view that MK and RK allow more comprehensive characterization of microstructural changes during children brain development, especially in PLIC and ALIC. Frontal-parietal white matter (FWM, PWM) reflected the degree of brain development in the front and middle brain. In this study, the FA values of PWM and FWM were lower than those in the term infant group. FWM was the language and motor center , so it was speculated that preterm infants lag behind full-term infants in language and motor development. Similarly, when PWM of premature babies was underdeveloped, the ability to integrate sensory and language was also lacking. The thalamus was the gray matter nucleus, one of the areas where neonatal metabolism was vigorous. Its myelin development was also very active. At the same time, the thalamus was also the highest sensory center and the most important sensory conduction relay station [16–18].The results showed that the FA value of TH was lower than that in term infants. It was assumed that premature babies were delayed in perception, cognition, and motor development. DKI can be used as an effective tool to assess brain developmental delay in premature infants.
By comparing DKI parameters in different brain regions between the two groups, we selected four ROIs with significant differences, including ALIC, PLIC, PWM and FWM. Our results shown that the area under curves (AUC) of MK in ALIC and PLIC were statistically significant. Studies have shown that neonatal brain development follows a backward-to-forward pattern. Due to early myelination of ALIC and PLIC, the metabolism is vigorous and the oxygen demand is high. When exposed to risk factors for preterm birth,the metabolically active areas are the first to be damaged. At the same time, MK can reflect the backward development of PLIC and ALIC by capturing the changes in microstructure. When brain development is impaired, the decreased density of cells and axon membranes may also lead to the decreased MK values, which are significantly different from those in the control group. In our study, FA did not show good diagnostic value in ALIC and PLIC. Because the internal capsule acts as a white matter plate connecting the upper and lower fibers of the cerebral cortex to the brainstem, the structure is more complicated. For this complex structure, the diffusion of water molecules actually deviates from the normal distribution, and MK can quantify this deviation.
RK represents the degree to which the molecular diffusion deviates radially from the Gaussian pattern. Compared with the FA value, RK changes more significantly in premature infants brain, which is confirmed in our study. The diagnostic value of RK in PWM was statistically significant. We speculated that the RK value may more sensitively reflect the limited radial diffusion of PWM.
With the same view as Vasung, the FA value of FWM has certain diagnostic value in premature infants with brain development disorders. There was a significant difference in the FA value of FWM. It may be because FA is mainly affected by cell changes and fiber bundle density, while MK is mainly affected by the complexity of the microstructure [24, 25]. Therefore, as a major functional area of the brain, we believe that FA value is sensitive in FWM.
This study confirmed that the correlations between MK, RK and PMA was higher than the correlations between FA, MD and PMA in the TH or CN. For homogeneous structures, such as gray matter, MK and RK are more sensitive than FA and MD. MK,RK played an important role in detecting the development of isotropic tissues (such as gray matter). In the gray matter region, the changes of MK and RK parameters may be related to the increased concentration of mature neuronal macromolecules and the decrease of tissue water content[27, 28], or to other special structures occurring in the development of gray matter. As an advanced and sensitive imaging technique, MK and RK can be used to detect the subtle structural changes of thalamic neurons in premature infants.MK and RK can show hidden manifestations that FA and MD cannot detect in vivo. Therefore, we speculate that the MK and RK parameters have an advantage in reflecting the development of the deep nucleus in premature infants. MK and RK parameters can better reflect the brain maturity of premature infants.
There were several limitations in this study. This study was only a cross-sectional study. The long-period developmental mechanism still need to be further verified by longitudinal data. In addition, the sample size was not large enough. Next we will continue to enlarge sample size. Finally, the PMA range of the research subjects was relatively large. If the same newborn brain template is used, the accuracy of image registration may be improved. The next step will be to establish brain templates for different PMA segments.