Department of Anatomy and Cell Biology, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA.
Department of Bioengineering, University of Illinois at Chicago, School of Engineering, Chicago, IL 60612, USA.
Brain Res. 2018 Jan 15;1679:45-52. doi: 10.1016/j.brainres.2017.11.017. Epub 2017 Nov 23.
Extensive pathological evidence indicates that axonal degeneration represents an early and critical event in amyotrophic lateral sclerosis (ALS). Unfortunately, few MRI studies have focused in the early detection of white matter (WM) alterations in the spinal cord region. To unveil these WM changes, we performed high resolution diffusion tensor imaging (DTI) and correlated the results with histological analysis of adjacent slices taken from the spinal cords of presymptomatic mice. The DTI studies demonstrated a significant reduction in fractional anisotropy (FA) as well as axial diffusivities (AD) and an increase in radial diffusivity (RD), predominantly at lower segments of the spinal cord. Increases in FA and a reduction in AD and RD were observed in spinal cord (SC) gray matter (GM). Diffusion changes are associated with early and progressive alterations in axonal connectivity following a distal to proximal progression. Histological data tagging neuronal, axonal and glial cell markers demonstrated presymptomatic alterations in spinal cord WM and GM. This study demonstrates that DTI methods are optimal preclinical imaging tools to detect structural anomalies in WM and GM spinal cord during early stages of the disease.
大量病理学证据表明，轴突变性是肌萎缩侧索硬化症（ALS）的早期关键事件。不幸的是，很少有 MRI 研究关注脊髓区域的白质（WM）早期改变。为了揭示这些 WM 变化，我们进行了高分辨率弥散张量成像（DTI），并将结果与取自无症状小鼠脊髓的相邻切片的组织学分析相关联。DTI 研究表明，FA 以及轴突弥散系数（AD）显著降低，而径向弥散系数（RD）增加，主要在脊髓的较低节段。在脊髓（SC）灰质（GM）中观察到 FA 增加和 AD 及 RD 减少。弥散变化与远端到近端进展后的轴突连接的早期和进行性改变有关。标记神经元、轴突和神经胶质细胞标志物的组织学数据表明，脊髓 WM 和 GM 在疾病早期就出现了改变。本研究表明，DTI 方法是在疾病早期检测 WM 和 GM 脊髓结构异常的最佳临床前成像工具。
