Spiral volumetric optoacoustic tomography of reduced oxygen saturation in the spinal cord of M83 mouse model of Parkinson's disease.

Abstract

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 (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. 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. 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.