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Blood-brain barrier disruption in experimental focal ischemia: comparison between in vivo MRI and immunocytochemistry
1Center for Imaging and Pharmaceutical Research, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
Abstract:
The definition of blood-brain barrier (BBB) damage in cerebral ischemia using contrast-enhanced MRI has not been clearly correlated to the spread of edema or other histological measures of barrier disruption. In this study, we used a rabbit model of focal cerebral ischemia to compare GdDTPA-enhanced MRI with spin-echo images of brain injury and immunocytochemical detection of BBB damage and vasogenic edema. After 4 h of transient ischemia followed by 6 h of reperfusion, in vivo T2W and T1W images were obtained in a 1.5 T magnet using a 3-inch surface coil. After MRI, the animals were sacrificed and anti-serum protein (IgG) monoclonal antibodies were used to detect regions of increased BBB permeability to serum proteins. Ischemic neuronal damage was confirmed with cresyl-violet histology. T2W scans showed focal regions of increased signal intensity in the ischemic hemisphere (17.0 +/- 4.1%) that primarily involved the cortex and striatum. T1W scans showed corresponding regions of hypointensity but demonstrated, in general, smaller lesion sizes (10.1 +/- 2.9%). GdDTPA-enhanced images showed variable areas of BBB disruption that included regions of intense leakage as well as lesions that only showed subtle enhancement along the periphery of damaged tissue. It appeared that large and more severe lesions corresponded to peripheral enhancement whereas smaller lesions showed central parenchymal enhancement. The extent of MR contrast enhancement did not correlate well with immunocytochemical images of serum protein leakage. Anti-IgG stains demonstrated widespread regions of BBB damage corresponding with areas of damaged neurons that appeared pyknotic on cresyl-violet sections.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Contrast-enhanced MRI shows blood-brain barrier damage in cerebral ischemia, but its correlation with edema and histological measures remains unclear. This study compared MRI findings with immunocytochemistry, revealing discrepancies in assessing blood-brain barrier permeability and edema extent.
Area of Science:
- Neuroimaging
- Cerebrovascular Research
- Histopathology
Background:
- Assessing blood-brain barrier (BBB) damage in cerebral ischemia via contrast-enhanced MRI lacks clear correlation with edema and histological damage.
- Understanding BBB disruption is crucial for evaluating stroke severity and guiding treatment.
Purpose of the Study:
- To compare Gadolinium-Diethylenetriaminepentaacetic acid (GdDTPA)-enhanced MRI with histological measures of BBB damage and edema in a rabbit model of focal cerebral ischemia.
- To investigate the correlation between MRI findings and immunocytochemical detection of BBB permeability and vasogenic edema.
Main Methods:
- Focal cerebral ischemia was induced in rabbits, followed by transient ischemia and reperfusion.
- In vivo T2-weighted and T1-weighted MRI scans were acquired using a 1.5 T magnet.
- Post-MRI, animals were sacrificed for immunocytochemical detection of serum protein (IgG) leakage and cresyl-violet histology for neuronal damage.
Main Results:
- T2W scans revealed increased signal intensity in the ischemic hemisphere (17.0 +/- 4.1%), primarily in the cortex and striatum.
- T1W scans showed smaller hypointense regions (10.1 +/- 2.9%).
- GdDTPA-enhanced MRI demonstrated variable BBB disruption, with enhancement patterns not consistently correlating with immunocytochemical IgG staining or histological damage.
Conclusions:
- MRI contrast enhancement extent did not strongly correlate with immunocytochemical BBB damage or vasogenic edema.
- Immunocytochemistry revealed widespread BBB damage and neuronal injury in ischemic regions.
- Further refinement is needed to accurately correlate MRI findings with the extent of blood-brain barrier disruption and edema in cerebral ischemia.