Direct and specific assessment of axonal injury and spinal cord microenvironments using diffusion correlation imaging

Abstract

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.

MRI metrics at the epicenter of spinal cord injury are correlated with the stepping process in rhesus monkeys

“…However, the diffusivity parallel to the axonal pathways remained stable after injury. This showed that the axonal pathways in the residual tissue were preserved [41,42] but underwent demyelination [43].…”

Multidimensional MRI for characterization of subtle axonal injury accelerated using an adaptive nonlocal multispectral filter

“…Multidimensional MRI is an emerging approach [37] that is now being applied to address a range of medical conditions such as prediction of pregnancy complications via placenta characterization [9], spinal cord injury [6,38], prostate cancer [39], breast cancer [40], and axonal injury due to TBI [22]. Recent in vivo proof-of-concept applications of subvoxel T 1 -T 2 correlation spectra using 105 images [41] and of subvoxel diffusion-T 1 correlation spectra using 363 [11] and 304 [42] images are promising.…”

Diffusion MRI Based Myometrium Tractography for Detection of Placenta Accreta Spectrum Disorder

“…Diffusion MRI (dMRI) is a widely used tool that characterizes the microstructural organization of biological tissues based on the diffusion behaviors of water molecules 17–19 . Due to the anisotropic diffusion of water molecules in fiber microstructures, dMRI can be used to reconstruct the fiber tracts 20 (so‐called tractography) in both brain white matter 21 and muscular tissues, such as skeletal muscle, 22 myocardium, 23 tongue, 24 and myometrium 25 .…”

“…Diffusion MRI (dMRI) is a widely used tool that characterizes the microstructural organization of biological tissues based on the diffusion behaviors of water molecules. [17][18][19] Due to the anisotropic diffusion of water molecules in fiber microstructures, dMRI can be used to reconstruct the fiber tracts 20 (so-called tractography) in both brain white matter 21 and muscular tissues, such as skeletal muscle, 22 myocardium, 23 tongue, 24 and myometrium. 25 The myometrium that is adhesive to the outer rim of the placenta is comprised of three layers-the subendometrium circular layer of myometrium that wraps the placenta in the coronal plane, the outer longitudinal layer that wraps the placenta in the sagittal plane, and the middle intertwined layer that comprises the major part of the myometrium.…”