Evaluating regional blood spinal cord barrier dysfunction following spinal cord injury using longitudinal dynamic contrast-enhanced MRI.
BACKGROUND
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.


METHODS
C57BL/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.


RESULTS
Quantitative 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.


CONCLUSIONS
The 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.
Tatar
Ilkan
I
Preclinical Imaging in Translational Research Laboratory, Radiology and Radiological Science, Medical University of South Carolina, 169 Ashley Avenue, Charleston, SC 29425, USA. ilkan@hacettepe.edu.tr
Chou
Peter Cheng-te
PC
Desouki
Mohamed Mokhtar
MM
El Sayed
Hanaa
H
Bilgen
Mehmet
M
D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D019786:Gadolinium DTPA; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D013119:Spinal Cord Injuries / Q000150:complications* / Q000175:diagnosis*; D020760:Spinal Cord Ischemia / Q000175:diagnosis* / Q000209:etiology*; D013382:Subtraction Technique
D003287:Contrast Media; D019786:Gadolinium DTPA