Introduction

Periventricular leukomalacia (PVL) is a major form of white matter (WM) injury due to hypoxic-ischemic encephalopathy, etc¹.There are two types of PVL (cystic and non-cystic). Compared with cystic PVL, a low morbidity of CP was found in non-cystic PVL^2,3 Up to now, the accurate prediction of CP outcome is still a big challenges in non-cystic PVL infants. However, early CP diagnosis is important for early treatment strategies. Therefore, this study aims to determine the crucial WM lesions in spastic cerebral palsy (SCP) in non-cystic PVL infants using diffusion tensor imaging (DTI).

Methods

15 PVL infants with SCP, 11 non-spastic PVL infants, and 17 normal control infants were retrospectively enrolled. The children with SCP were diagnosed by two pediatric neurologists. MR examinations were performed between the ages of 6–18 months using a 3T scanner (GE, Signa HDxt) with an 8-channel head coil. The protocols sequence included 3D-MPRAGE T1WI(TR/TE, 10ms/4.6ms; matrix, 256×256; section-thickness, 1mm; FOV, 240mm), FSE-T2WI (TR/TE, 6500ms/124ms; matrix, 256×256; section-thickness, 4mm; FOV, 180mm) and DTI(35 directions; b-value, 1000 s/mm2; TR/TE, 5500ms/95ms; section-thickness,4mm; FOV, 180mm, matrix, 256×256). DTI data was processed with the aid of the FMRIB software library (FSL, www.fmrib.ox.au.uk/fsl). TBSS was used to align FA images of all subjects to the target image. The mean FA image and its skeleton were created. Each subject’s aligned FA images were projected onto the mean FA skeleton (threshold=0.2). Voxel-wise, cross-subject statistics was performed to assess differences in FA between bilateral SCP, No-CP, and control groups. Additionally, automated fiber-tract quantification (AFQ) software tools were used to identify WM tracts in each participant's brain (https://github.com/jyeatman/AFQ). The FA values along the core fiber which are plotted for 100 equidistant locations between two defining ROIs were compared between the groups. All statistical analysis were performed by using SPSS 17.0 and p<0.05 was considered as statistically significant difference.

Results

Group comparison of FA values between bilateral SCP, No-CP, and control groups were shown by TBSS maps(Fig.1). Compared with the control group, there was a significant decrease in FA in widespread areas of white matter in the PVL infants with SCP, while the FA decrease was mainly in the posterior white matter of the non-spastic infants (P<0.05). Compared with the non-spastic PVL infants, the SCP infants showed significantly lower FA values in regional WM, including bilateral cerebral peduncle, posterior limb of the internal capsule, corona radiata, external capsule, genu and splenium of corpus callosum (P<0.05).The AFQ results showed a decrease in FA in the bilateral corticospinal tract (CST) only in infants with SCP. The other tract profiles (posterior thalamic radiation, genu, and the splenium of corpus callosum) showed decreased FA values in both the bilateral SCP and No-CP groups (P<0.05) (Fig.2).

Discussion

This study found that PVL infants with bilateral SCP showed significantly lower FA values in regional WM, e.g. the cerebral peduncle，posterior limb of the internal capsule and corona radiata, than PVL infants without CP. There were deceased FA values, specifically along the CST, in the bilateral SCP group, but not in the No-CP group. Meanwhile, the posterior thalamic radiation, and the splenium of corpus callosum were damaged both in SCP and No-CP PVL infants due to immature blood vessels, pressure passive circulation, and selective vulnerability of preoligodendrocytes⁴. These results provide additional evidence that lesions in the CST may be the crucially damaged WM in bilateral SCP related to motor impairment. All these suggest that the CST may play a more important role than the other WM tracts in causing motor impairment.

Conclusion

Lower FA in the CST maybe a prerequisite and biomarker for identifying and predicting the outcome of SCP in infants with PVL.

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2016YFC0100300), National Natural Science Foundation of China (No.81171317, 81471631), and the 2011 New Century Excellent Talent Support Plan of the Ministry of Education, China (NCET-11-0438).

References

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