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

Tatar I, Chou PC, Desouki MM, El Sayed H, Bilgen M - BMC Med Imaging (2009)

Bottom Line: 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.Diffusion computations included longitudinal and transverse diffusivities and fractional anisotropy index.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

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LFB, NSE and CD34 stained contiguous slices at the injury epicenter and at a normal section rostral to the epicenter. In the rostral segment (top row), LFB (a) and NSE (b) stains show normal myelination and intact neurons, and CD34 stain (c) shows intact vasculature. At the epicenter (bottom row), LFB (d) and NSE (e) stains show diffuse demyelination and damaged neurons, and the corresponding CD34 stain (f) shows damaged vasculature with leaky BSCB.
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Figure 9: LFB, NSE and CD34 stained contiguous slices at the injury epicenter and at a normal section rostral to the epicenter. In the rostral segment (top row), LFB (a) and NSE (b) stains show normal myelination and intact neurons, and CD34 stain (c) shows intact vasculature. At the epicenter (bottom row), LFB (d) and NSE (e) stains show diffuse demyelination and damaged neurons, and the corresponding CD34 stain (f) shows damaged vasculature with leaky BSCB.

Mentions: Figures 7, 8 and 9 show histologic sections stained with H&E, LFB, NSE or CD34. The slice in Figure 7 matches the images in Figure 6, but the others in Figures 8 and 9 are from a different injured SC. The vasculature was depicted by H&E staining in Figure 7 and better outlined in Figure 8 by CD34 immunostaining. The microscopic features of the neurovascular pathology revealed partially intact GM at the ventral horns, significant damage at the dorsal SC with substantial loss of tissue matrix and also small cavities distributed throughout the cord, but generally more prominent in WM than GM. These regions were evaluated more closely at higher magnification in three selected regions of interest – windows 1, 2 and 3. As expected, in the normal looking GM (window 1), the vessels were observed to be intact but mostly ruptured in the damaged region (window 2) that led to the extravasation of the red blood cells. The periphery of the damaged SC region (window 3) contained cavities that colocalized with small vessels or endothelial cells.


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

Tatar I, Chou PC, Desouki MM, El Sayed H, Bilgen M - BMC Med Imaging (2009)

LFB, NSE and CD34 stained contiguous slices at the injury epicenter and at a normal section rostral to the epicenter. In the rostral segment (top row), LFB (a) and NSE (b) stains show normal myelination and intact neurons, and CD34 stain (c) shows intact vasculature. At the epicenter (bottom row), LFB (d) and NSE (e) stains show diffuse demyelination and damaged neurons, and the corresponding CD34 stain (f) shows damaged vasculature with leaky BSCB.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2714086&req=5

Figure 9: LFB, NSE and CD34 stained contiguous slices at the injury epicenter and at a normal section rostral to the epicenter. In the rostral segment (top row), LFB (a) and NSE (b) stains show normal myelination and intact neurons, and CD34 stain (c) shows intact vasculature. At the epicenter (bottom row), LFB (d) and NSE (e) stains show diffuse demyelination and damaged neurons, and the corresponding CD34 stain (f) shows damaged vasculature with leaky BSCB.
Mentions: Figures 7, 8 and 9 show histologic sections stained with H&E, LFB, NSE or CD34. The slice in Figure 7 matches the images in Figure 6, but the others in Figures 8 and 9 are from a different injured SC. The vasculature was depicted by H&E staining in Figure 7 and better outlined in Figure 8 by CD34 immunostaining. The microscopic features of the neurovascular pathology revealed partially intact GM at the ventral horns, significant damage at the dorsal SC with substantial loss of tissue matrix and also small cavities distributed throughout the cord, but generally more prominent in WM than GM. These regions were evaluated more closely at higher magnification in three selected regions of interest – windows 1, 2 and 3. As expected, in the normal looking GM (window 1), the vessels were observed to be intact but mostly ruptured in the damaged region (window 2) that led to the extravasation of the red blood cells. The periphery of the damaged SC region (window 3) contained cavities that colocalized with small vessels or endothelial cells.

Bottom Line: 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.Diffusion computations included longitudinal and transverse diffusivities and fractional anisotropy index.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus