Friesen Emma, Gosal Rubeena, Herrera Sheryl, Mercredi Morgan, Buist Richard, Matsuda Kant, Martin Melanie
Department of Chemistry, University of Winnipeg, Winnipeg, MB, Canada.
Department of Physics, University of Winnipeg, Winnipeg, MB, Canada.
Magn Reson Imaging. 2025 Jan;115:110255. doi: 10.1016/j.mri.2024.110255. Epub 2024 Oct 12.
Degeneration of white matter (WM) microstructure in the central nervous system is characteristic of many neurodegenerative conditions. Previous research indicates that axonal degeneration visible in ex vivo electron microscopy (EM) photomicrographs precede the onset of clinical symptoms. Measuring WM microstructural features, such as axon diameter and packing fraction, currently require these highly invasive methods of analysis and it is therefore of great importance to develop methods for in vivo measurements. Diffusion weighted Magnetic Resonance Imaging (MRI) is a non-invasive method which can be used in conjunction with temporal diffusion spectroscopy (TDS) and an oscillating gradient spin echo (OGSE) pulse sequence to probe micron-scale structures within neural tissue. The current experiment aims to compare axon diameter measurements, mean effective axon diameter (AxD¯), and packing fractions calculated from EM histopathological analysis and inferred values from MR images. Mathematical models of axon diameters used for analysis include the ActiveAx Frequency-Dependent Extra-Axonal Diffusion (AAD) model and the AxCaliber Frequency-Dependent Extra-Axonal Diffusion (ACD) model using ROI (Region of Interest) based analysis (RBA) and voxel-based analysis (VBA), respectively. Overall, it was observed that MRI inferred WM microstructural parameters overestimate those calculated from EM. This may be attributable to tissue shrinkage during EM dehydration, the sensitivity of MR pulse sequences to larger diameter axons, and/or inaccurate model assumptions. The results of the current study provide a means to characterize the precision and accuracy of RBA-ACD and VBA-AAD OGSE-TDS and highlight the need for further research investigating the relationship between ex vivo MRI and EM, with the goal of reaching in vivo MRI.
中枢神经系统白质（WM）微观结构的退化是许多神经退行性疾病的特征。先前的研究表明，在离体电子显微镜（EM）显微照片中可见的轴突退化先于临床症状的出现。测量WM微观结构特征，如轴突直径和堆积分数，目前需要这些高度侵入性的分析方法，因此开发体内测量方法非常重要。扩散加权磁共振成像（MRI）是一种非侵入性方法，可与时间扩散光谱（TDS）和振荡梯度自旋回波（OGSE）脉冲序列结合使用，以探测神经组织内的微米级结构。当前实验旨在比较轴突直径测量值、平均有效轴突直径（AxD¯），以及由EM组织病理学分析计算得出的堆积分数和从MR图像推断的值。用于分析的轴突直径数学模型分别包括基于感兴趣区域（ROI）分析（RBA）的ActiveAx频率依赖性轴外扩散（AAD）模型和基于体素分析（VBA）的AxCaliber频率依赖性轴外扩散（ACD）模型。总体而言，观察到MRI推断的WM微观结构参数高估了由EM计算得出的参数。这可能归因于EM脱水过程中的组织收缩、MR脉冲序列对较大直径轴突的敏感性，和/或不准确的模型假设。当前研究结果提供了一种表征RBA - ACD和VBA - AAD OGSE - TDS精度和准确性的方法，并强调需要进一步研究离体MRI与EM之间的关系，目标是实现体内MRI。
