Abstract
BackgroundIn vivo preclinical imaging of spinal cord injury (SCI) in rodent models provides clinically relevant information in translational research. This paper uses multimodal magnetic resonance imaging (MRI) to investigate neurovascular pathology and changes in blood spinal cord barrier (BSCB) permeability following SCI in a mouse model of SCI.MethodsC57BL/6 female mice (n = 5) were subjected to contusive injury at the thoracic T11 level and scanned on post injury days 1 and 3 using anatomical, dynamic contrast-enhanced (DCE-MRI) and diffusion tensor imaging (DTI). The injured cords were evaluated postmortem with histopathological stains specific to neurovascular changes. A computational model was implemented to map local changes in barrier function from the contrast enhancement. The area and volume of spinal cord tissue with dysfunctional barrier were determined using semi-automatic segmentation.ResultsQuantitative maps derived from the acquired DCE-MRI data depicted the degree of BSCB permeability variations in injured spinal cords. At the injury sites, the damaged barriers occupied about 70% of the total cross section and 48% of the total volume on day 1, but the corresponding measurements were reduced to 55% and 25%, respectively on day 3. These changes implied spatio-temporal remodeling of microvasculature and its architecture in injured SC. Diffusion computations included longitudinal and transverse diffusivities and fractional anisotropy index. Comparison of permeability and diffusion measurements indicated regions of injured cords with dysfunctional barriers had structural changes in the form of greater axonal loss and demyelination, as supported by histopathologic assessments.ConclusionThe results from this study collectively demonstrated the feasibility of quantitatively mapping regional BSCB dysfunction in injured cord in mouse and obtaining complementary information about its structural integrity using in vivo DCE-MRI and DTI protocols. This capability is expected to play an important role in characterizing the neurovascular changes and reorganization following SCI in longitudinal preclinical experiments, but with potential clinical implications.
Highlights
In vivo preclinical imaging of spinal cord injury (SCI) in rodent models provides clinically relevant information in translational research
The surgical procedures, injuries, and prolonged anesthesia during magnetic resonance imaging (MRI) scans were well tolerated by all mice
The intensity contrasts on these images from normal sections delineate gross anatomical details of the cord within the white matter (WM) and grey matter (GM) as well as the surrounding spinal structures
Summary
In vivo preclinical imaging of spinal cord injury (SCI) in rodent models provides clinically relevant information in translational research. This paper uses multimodal magnetic resonance imaging (MRI) to investigate neurovascular pathology and changes in blood spinal cord barrier (BSCB) permeability following SCI in a mouse model of SCI. Knowledge of barrier properties and its status is essential if potential intravascular drugs with capabilities to improve neurovascular protection and to promote repair and recovery will be administered. Such treatment is possible provided that the drugs can pass through the open barriers to reach the destined regions in the SC parenchyma. A complete understanding of the vascular response to spinal cord injury (SCI) is required for developing intervention strategies aimed at rapidly restoring the barrier integrity as well as blood supply to the ischemic areas of the traumatized cord
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