Supplementary Material for: Distinguishing Laterality in Brain Injury in Rabbit Fetal MRI Using Novel Volume Rendering Techniques

Introduction: Our laboratory has been exploring the MRI detection of fetal brain injury, which previously provided a prognostic biomarker for newborn hypertonia in an animal model of cerebral palsy (CP). The biomarker relies on distinct patterns of diffusion-weighted imaging-defined apparent diffusion coefficient (ADC) in fetal brains during uterine ischemia (H-I). Despite the challenges posed by small brains and tissue acquisition, our objective was to differentiate between left and right brain ADC changes. Methods: A novel aspect involved utilizing three-dimensional rendering techniques to refine ADC measurements within spheroids encompassing fetal brain tissue. 25-day gestation rabbit fetuses underwent global hypoxia due to maternal uterine ischemia. Results: Successful differentiation of left and right brain regions was achieved in 28% of the fetal brains. Ordinal analysis revealed predominantly higher ADC on the left side compared to the right at baseline and across the entire time series. During H-I and reperfusion-reoxygenation, the right side exhibited a favored percentage change. Among these fetal brains, 73% exhibited the ADC pattern predictive of hypertonia. No significant differences between left and right sides were observed in patterns predicting hypertonia, except for one time point during hypoxia-ischemia. This study also highlights a balance between left-sided and right-sided alterations within the population.
Conclusion: This study emphasizes the importance of investigating laterality and asymmetric hemispheric lesions for early diagnosis of brain injury leading to CP. The technological limitations in obtaining a clear picture of the entire fetal brain for every fetus mirror the challenges encountered in human studies.

引言：本实验室长期开展磁共振成像（Magnetic Resonance Imaging, MRI）检测胎儿脑损伤的相关研究，此前曾在脑瘫（Cerebral Palsy, CP）动物模型中，为新生儿肌张力增高症筛选出一款预后生物标志物。该生物标志物基于子宫缺血（H-I）状态下胎儿脑内弥散加权成像（Diffusion-Weighted Imaging, DWI）定义的表观扩散系数（Apparent Diffusion Coefficient, ADC）特征模式。尽管受限于脑组织体积微小且样本获取难度大，本研究的目标仍是区分左右脑的ADC变化特征。

方法：本研究的创新点在于采用三维渲染技术，优化包裹胎儿脑组织的球体区域内的ADC测量流程。实验对象为因母体子宫缺血诱发全脑缺氧的妊娠25天兔胎。

结果：28%的胎儿脑成功实现左右脑区域的区分。有序分析显示，在基线状态及整个时间序列中，左侧脑的ADC值整体高于右侧。在子宫缺血（H-I）及再灌注-复氧阶段，右侧脑的ADC百分比变化更为显著。其中73%的胎儿脑呈现出与肌张力增高症相关的ADC特征模式。在该特征模式下，除缺氧缺血期间的一个时间点外，左右脑间未观察到显著差异。本研究还揭示了群体层面左右脑改变的平衡特征。

结论：本研究强调，针对导致脑瘫的脑损伤进行早期诊断时，需重视偏侧性及半球不对称病变的研究价值。为每一例胎儿获取完整清晰的全脑影像所面临的技术限制，与人类临床研究中遇到的挑战相一致。