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MRI measurement of blood-brain barrier permeability followingspontaneous reperfusion in the starch microsphere model of ischemia.
Harris N.G, Gauden V, Fraser P.A, Williams SR, Parker GJM
Magnetic Resonance Imaging. 2002;20.
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Abstract
Quantification of the acute increases in blood-brain barrier (BBB) permeability that occur subsequent to experimental ischemic injuryhas been limited to single time-point, invasive methodologies. Although permeability can be qualitatively assessed to visualise regionalchanges during sequential studies on the same animal using contrast-enhanced magnetic resonance imaging (MRI), quantitative informationon the magnitude of change is required to compare barrier function during sequential studies on the same animal or between differentanimals. Recently, improvements in MRI tracer kinetic models and in MR hardware design mean that an estimate of permeability in vivocan now be obtained with acceptable accuracy and precision. We report here the use of such methods to study acute changes followingspontaneous reperfusion in an animal model of ischemia. We have obtained estimates of BBB permeability following spontaneousreperfusion, subsequent to forebrain ischemia by unilateral carotid injection of starch microspheres in the rat. T2*-weighted anddiffusion-trace imaging were used to monitor the initial reduction in CBF and the time-course of ischemia, respectively. Followingreperfusion, an intraveneous bolus of dimeglumine gadopentetate (Gd-DTPA) and horseradish peroxidase (HRP) was given during acontinuous acquisition of T1 maps with a 48s temporal resolution. Permeability maps were constructed using a 4-compartment model; Ktrans,the permeability-surface area product of the capillary walls was estimated to be 9.2 0.6 10 4 min 1 in the cortex. Visualisation of theregional extent of HRP extravasation on histological sections following termination of the experiment demonstrated very little correspondenceto the region of Gd-DTPA leakage. Quantitative MRI assessment of BBB permeability following ischemia-reperfusion is consistentwith published values obtained by invasive methods. Differences between Gd-DTPA-enhancement and HRP may reflect differences in themolecular size of the tracers.