Blood‐brain barrier permeability in rats is altered by exposure to magnetic fields associated with magnetic resonance imaging at 1.5 T

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Abstract
We have previously reported that exposure of rats to low-field (0.15 T) magnetic resonance imaging (MRI) increases blood-brain barrier (BBB) permeability. However, a number of investigators have failed to observe this effect when high-field MRI (1.5 T or higher) is used. Therefore, we investigated whether or not we would observe changes using our technique at these higher fields. Adult male Sprague-Dawley rats were anaesthetised and then exposed to a 22.5 min imaging or sham procedure. Immediately following exposure, rats were injected with 1 MBq of 153Gd-DTPA intracardially and then immediately re-exposed for an additional 22.5 min. The rats were killed 1h following the second MRI exposure, at which time the brain was resected and 3ml of venous blood collected. The ratio of radioactivity per gram of brain to radioactivity per per milliliter of blood, known as the brain-blood partition coefficient, was determined and used as a measure of BBB permeability. Groups of animals had different exposures. Group 1 (n = 9) was exposed to a clinically relevant MRI procedure. Group 2 (n = 20) was exposed to the same procedure except the rf specific absorption rate (SAR) was reduced to 25% and the animals were positioned 15 cm from imager centre to increase the time-varying magnetic field from 0.4 to 2.8 T/s. For the sham exposures (n = 21), the animals were placed in the imager with the static field ramped down to zero and exposed to a sound recording simulating a MRI examination. In a third group (n = 11), exposure to only the static 1.5 T was investigated, while in a fourth group (n = 15), the exposure field was only to a static 1.89 T. Sham controls for groups 3 (n = 12) and 4 (n = 19) were silent. Group 1 showed an increase in BBB permeability (5.7 ± 0.5, mean ± SEM, P < 0.04, n = 9); however, group 2 showed a decrease (3.9 ± 0.2, P < 0.002, n = 20). Static field exposure of 1.5 T increased permeability (5.7 ± 0.5, P < 0.05, n = 11) as did 1.89 T (4.7 ± 0.4, P < 0.02, n = 15). Although there was no difference between sound and silent shams, shams done at night (4.8 ± 0.2, n = 32) were significantly greater (P < 0.0004) than those done during the day (3.7 ± 0.2, n = 19). Our results suggest changes in the rf and/or gradient field exposure can produce opposite effects on BBB permeability. Further, experiments involving only rf and only gradient field exposure are needed. The estimation of changes in BBB permeability by measuring the partition coefficient of compounds normally excluded by the BBB offers an objective quantitative technique which can detect changes of the order of 25%. This sensitivity is needed to explore the important, albeit subtle, effects of magnetic fields.