The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20817, USA; The Center for Neuroscience and Regenerative Medicine, Uniformed Service University of the Health Sciences, Bethesda, MD 20814, USA.
The Department of Biomedical Engineering, The University of Arizona, Tucson, Arizona 85721, USA.
Neuroimage. 2020 Nov 1;221:117195. doi: 10.1016/j.neuroimage.2020.117195. Epub 2020 Jul 26.
We describe a practical two-dimensional (2D) diffusion MRI framework to deliver specificity and improve sensitivity to axonal injury in the spinal cord. This approach provides intravoxel distributions of correlations of water mobilities in orthogonal directions, revealing sub-voxel diffusion components. Here we use it to investigate water diffusivities along axial and radial orientations within spinal cord specimens with confirmed, tract-specific axonal injury. First, we show using transmission electron microscopy and immunohistochemistry that tract-specific axonal beading occurs following Wallerian degeneration in the cortico-spinal tract as direct sequelae to closed head injury. We demonstrate that although some voxel-averaged diffusion tensor imaging (DTI) metrics are sensitive to this axonal injury, they are non-specific, i.e., they do not reveal an underlying biophysical mechanism of injury. Then we employ 2D diffusion correlation imaging (DCI) to improve discrimination of different water microenvironments by measuring and mapping the joint water mobility distributions perpendicular and parallel to the spinal cord axis. We determine six distinct diffusion spectral components that differ according to their microscopic anisotropy and mobility. We show that at the injury site a highly anisotropic diffusion component completely disappears and instead becomes more isotropic. Based on these findings, an injury-specific MR image of the spinal cord was generated, and a radiological-pathological correlation with histological silver staining % area was performed. The resulting strong and significant correlation (r=0.70,p < 0.0001) indicates the high specificity with which DCI detects injury-induced tissue alterations. We predict that the ability to selectively image microstructural changes following axonal injury in the spinal cord can be useful in clinical and research applications by enabling specific detection and increased sensitivity to injury-induced microstructural alterations. These results also encourage us to translate DCI to higher spatial dimensions to enable assessment of traumatic axonal injury, and possibly other diseases and disorders in the brain.
我们描述了一种实用的二维（2D）扩散 MRI 框架，以提供特异性并提高脊髓轴突损伤的敏感性。该方法提供了各向异性水迁移率的体素内分布，揭示了亚体素扩散分量。在这里，我们使用它来研究具有明确的、束特异性轴突损伤的脊髓标本中沿轴向和径向方向的水扩散率。首先，我们通过透射电子显微镜和免疫组织化学显示，皮质脊髓束中的束特异性轴突珠状形成发生在沃勒变性之后，这是闭合性颅脑损伤的直接后果。我们证明，尽管一些体素平均扩散张量成像（DTI）指标对这种轴突损伤敏感，但它们是非特异性的，即它们不能揭示损伤的潜在生物物理机制。然后，我们采用 2D 扩散相关成像（DCI）通过测量和绘制与脊髓轴垂直和平行的水迁移率分布来改善对不同水微环境的区分。我们确定了六个不同的扩散光谱分量，它们根据其微观各向异性和迁移率而有所不同。我们表明，在损伤部位，高度各向异性的扩散分量完全消失，取而代之的是更各向同性的扩散分量。基于这些发现，生成了脊髓的损伤特异性 MR 图像，并与组织银染色%面积进行了放射病理学相关性分析。结果表明，相关性很强且具有统计学意义（r=0.70，p<0.0001），这表明 DCI 检测损伤诱导的组织改变具有很高的特异性。我们预测，选择性成像脊髓轴突损伤后微观结构变化的能力可以通过特异性检测和增加对损伤诱导的微观结构改变的敏感性，在临床和研究应用中非常有用。这些结果还鼓励我们将 DCI 转化为更高的空间维度，以评估创伤性轴突损伤，以及可能的大脑中的其他疾病和障碍。
