Combes Benjamin F, Kalva Sandeep Kumar, Benveniste Pierre-Louis, Tournant Agathe, Law Man Hoi, Newton Joshua, Krüger Maik, Weber Rebecca Z, Dias Inês, Noain Daniela, Dean-Ben Xose Luis, Konietzko Uwe, Baumann Christian R, Gillberg Per-Göran, Hock Christoph, Nitsch Roger M, Cohen-Adad Julien, Razansky Daniel, Ni Ruiqing
Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
Institute for Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland.
Eur J Nucl Med Mol Imaging. 2025 Jan;52(2):427-443. doi: 10.1007/s00259-024-06938-w. Epub 2024 Oct 9.
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.
In vivo spiral volumetric optoacoustic tomography (SVOT) was performed to assess oxygen saturation (sO) 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.
In vivo SVOT imaging revealed a lower sO 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.
We developed tools for deep-learning-based analysis for the segmentation of mouse spinal cord structural MRI data, and volumetric analysis of sO data. We demonstrated non-invasive high-resolution imaging of reduced sO in the absence of volumetric structural changes in the spinal cord of PD M83 mouse model.
中枢神经系统的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。在此，我们采用多模态成像方法，评估与非转基因同窝小鼠相比，过表达突变型A53Tα-突触核蛋白形式的转基因M83小鼠模型脊髓中的氧合变化。
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（sO）。使用9.4T的离体高场T1加权（T1w）磁共振成像（MRI）来评估脊髓的体积变化。开发了用于小鼠脊髓T1w MRI数据的3D SVOT分析和基于深度学习的自动分割以进行定量。在MRI扫描后进行磷酸化α-突触核蛋白（pS129α-突触核蛋白）以及血管组织（CD31和GLUT1）的免疫染色。
体内SVOT成像显示，在低于100μm的空间分辨率下，与非转基因同窝小鼠相比，M83小鼠脊髓中的sO较低。在50μm的空间分辨率下，由内部开发的基于深度学习的自动分割辅助的离体MRI（经手动分析验证）显示，与非转基因同窝小鼠相比，M83小鼠脊髓中没有体积萎缩。在存在pS129α-突触核蛋白积累的情况下，M83小鼠脊髓中的血管网络未受损。
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数据的分割以及sO数据的体积分析。我们展示了在PD M83小鼠模型脊髓中不存在体积结构变化的情况下，对降低的sO进行非侵入性高分辨率成像。
