Purpose

Metabolism and bioenergetics in the central nervous system play important roles in the pathophysiology of Parkinson’s disease (PD). Here, we employed a multimodal imaging approach to assess oxygenation changes in the spinal cord of the transgenic M83 murine model of PD overexpressing the mutated A53T alpha-synuclein form in comparison with non-transgenic littermates.

Methods

In vivo spiral volumetric optoacoustic tomography (SVOT) was performed to assess oxygen saturation (sO₂) in the spinal cords of M83 mice and non-transgenic littermates. Ex vivo high-field T1-weighted (T1w) magnetic resonance imaging (MRI) at 9.4T was used to assess volumetric alterations in the spinal cord. 3D SVOT analysis and deep learning-based automatic segmentation of T1w MRI data for the mouse spinal cord were developed for quantification. Immunostaining for phosphorylated alpha-synuclein (pS129 α-syn), as well as vascular organization (CD31 and GLUT1), was performed after MRI scan.

Results

In vivo SVOT imaging revealed a lower sO₂^SVOT in the spinal cord of M83 mice compared to non-transgenic littermates at sub-100 μm spatial resolution. Ex vivo MRI-assisted by in-house developed deep learning-based automatic segmentation (validated by manual analysis) revealed no volumetric atrophy in the spinal cord of M83 mice compared to non-transgenic littermates at 50 μm spatial resolution. The vascular network was not impaired in the spinal cord of M83 mice in the presence of pS129 α-syn accumulation.

Conclusion

We developed tools for deep-learning-based analysis for the segmentation of mouse spinal cord structural MRI data, and volumetric analysis of sO₂^SVOT data. We demonstrated non-invasive high-resolution imaging of reduced sO₂^SVOT in the absence of volumetric structural changes in the spinal cord of PD M83 mouse model.

中文翻译：

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帕金森病 M83 小鼠脊髓氧饱和度降低的螺旋体积光声断层扫描

 目的

中枢神经系统的新陈代谢和生物能量学在帕金森病 （PD） 的病理生理学中起重要作用。在这里，我们采用多模态成像方法来评估与非转基因同窝同窝小鼠相比，过表达突变的 A53T α-突触核蛋白形式的 PD 的转基因 M83 小鼠模型脊髓的氧合变化。

 方法

进行体内螺旋体积光声断层扫描 （SVOT） 以评估 M83 小鼠和非转基因同窝小鼠脊髓中的氧饱和度 （sO₂）。使用 9.4T 的离体高场 T1 加权 （T1w） 磁共振成像 （MRI） 评估脊髓的体积变化。开发了 3D SVOT 分析和基于深度学习的小鼠脊髓 T1w MRI 数据自动分割用于量化。MRI 扫描后对磷酸化 α-突触核蛋白 （pS129 α-syn） 以及血管组织 （CD31 和 GLUT1） 进行免疫染色。

 结果

体内 SVOT 成像显示，在亚 100 μm 空间分辨率下，与非转基因同窝小鼠相比，M83 小鼠脊髓中的 sO₂^SVOT 较低。由内部开发的基于深度学习的自动分割（通过人工分析验证）辅助的离体 MRI 显示，在 50 μm 空间分辨率下，与非转基因同窝小鼠相比，M83 小鼠的脊髓没有体积萎缩。在 pS129 α-syn 积累存在的情况下，M83 小鼠脊髓中的血管网络未受损。

 结论

我们开发了基于深度学习的分析工具，用于小鼠脊髓结构 MRI 数据的分割和 sO₂^SVOT 数据的体积分析。我们展示了在 PD M83 小鼠模型的脊髓没有体积结构变化的情况下，sO₂^SVOT 降低的无创高分辨率成像。