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Optical imaging to map blood-brain barrier leakage.

Jaffer H, Adjei IM, Labhasetwar V - Sci Rep (2013)

Bottom Line: Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB).The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations.The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.

ABSTRACT
Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB). We have developed an optical imaging method, based on excitation and emission spectra of Evans Blue dye, that is >1000-fold more sensitive than conventional ultraviolet spectrophotometry. We used a rat thromboembolic stroke model to validate the usefulness of our method for vascular leakage. Optical imaging data show that vascular leakage varies in different areas of the post-stroke brain and that administering tissue plasminogen activator causes further leakage. The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations. The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

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Vascular leakage in stroke.(a) Photographic image of a stroke brain harvested 2 hrs following EB injection which is 5 hr after induction of stroke. Arrow indicates the infarcted side of the brain. (b) Optical imaging of whole brain, areas of leakage is evident from color codes. (c) Optical imaging of brain slices that show vascular leakage. Areas with more leakage show as red, those with less leakage as blue. A filter paper disc loaded with 20 ng EB dye was used as an internal standard. (d) Photographic images of brain slices showing blue color of EB.
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f2: Vascular leakage in stroke.(a) Photographic image of a stroke brain harvested 2 hrs following EB injection which is 5 hr after induction of stroke. Arrow indicates the infarcted side of the brain. (b) Optical imaging of whole brain, areas of leakage is evident from color codes. (c) Optical imaging of brain slices that show vascular leakage. Areas with more leakage show as red, those with less leakage as blue. A filter paper disc loaded with 20 ng EB dye was used as an internal standard. (d) Photographic images of brain slices showing blue color of EB.

Mentions: The photograph of the entire brain harvested 2 hrs following infusion of EB (5 hrs after stroke induction) showed slightly blue discoloration of the stroke side of the brain due to extravasation of the injected EB dye (Fig. 2a). However, optical imaging of the same brain clearly showed areas of vascular leakage, obtained from the emission of optical signals from the EB accumulated in the infarcted brain (Fig. 2b). Since animals were perfused extensively with saline prior to harvesting the brain, the imaging signal seen is due to the EB localized in the brain tissue. Similar to color codes seen in the standard plot by optical imaging with EB amount (Fig. 1b), the areas with more EB leakage appeared red, those with less leakage as blue-grey, and areas of intermediate leakage appeared yellow (Fig. 2b). The corresponding brain slices showed similar color-coding as in intact brain (Fig. 2c). The regular photographic images of the same brain slices showed blue color of EB but it is difficult to distinguish areas of low or high EB leakage from these images as from optical images (Fig. 2c vs. 2d).


Optical imaging to map blood-brain barrier leakage.

Jaffer H, Adjei IM, Labhasetwar V - Sci Rep (2013)

Vascular leakage in stroke.(a) Photographic image of a stroke brain harvested 2 hrs following EB injection which is 5 hr after induction of stroke. Arrow indicates the infarcted side of the brain. (b) Optical imaging of whole brain, areas of leakage is evident from color codes. (c) Optical imaging of brain slices that show vascular leakage. Areas with more leakage show as red, those with less leakage as blue. A filter paper disc loaded with 20 ng EB dye was used as an internal standard. (d) Photographic images of brain slices showing blue color of EB.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814906&req=5

f2: Vascular leakage in stroke.(a) Photographic image of a stroke brain harvested 2 hrs following EB injection which is 5 hr after induction of stroke. Arrow indicates the infarcted side of the brain. (b) Optical imaging of whole brain, areas of leakage is evident from color codes. (c) Optical imaging of brain slices that show vascular leakage. Areas with more leakage show as red, those with less leakage as blue. A filter paper disc loaded with 20 ng EB dye was used as an internal standard. (d) Photographic images of brain slices showing blue color of EB.
Mentions: The photograph of the entire brain harvested 2 hrs following infusion of EB (5 hrs after stroke induction) showed slightly blue discoloration of the stroke side of the brain due to extravasation of the injected EB dye (Fig. 2a). However, optical imaging of the same brain clearly showed areas of vascular leakage, obtained from the emission of optical signals from the EB accumulated in the infarcted brain (Fig. 2b). Since animals were perfused extensively with saline prior to harvesting the brain, the imaging signal seen is due to the EB localized in the brain tissue. Similar to color codes seen in the standard plot by optical imaging with EB amount (Fig. 1b), the areas with more EB leakage appeared red, those with less leakage as blue-grey, and areas of intermediate leakage appeared yellow (Fig. 2b). The corresponding brain slices showed similar color-coding as in intact brain (Fig. 2c). The regular photographic images of the same brain slices showed blue color of EB but it is difficult to distinguish areas of low or high EB leakage from these images as from optical images (Fig. 2c vs. 2d).

Bottom Line: Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB).The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations.The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.

ABSTRACT
Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB). We have developed an optical imaging method, based on excitation and emission spectra of Evans Blue dye, that is >1000-fold more sensitive than conventional ultraviolet spectrophotometry. We used a rat thromboembolic stroke model to validate the usefulness of our method for vascular leakage. Optical imaging data show that vascular leakage varies in different areas of the post-stroke brain and that administering tissue plasminogen activator causes further leakage. The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations. The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

Show MeSH
Related in: MedlinePlus