MAGNETIC-RESONANCE-IMAGING INVESTIGATION OF BLOOD-BRAIN-BARRIER DAMAGE IN ADOPTIVE TRANSFER EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Recent advances in fast magnetic resonance imaging (MRI) techniques have allowed quantification of parameters such as Tl relaxation time, which can be modified by changes in the water content of a tissue. We have used this new method to study the evolution of blood-brain barrier (BBB) changes after adoptive transfer of MBP-specific (AT-EAE) and ovalbumin-specific T cell lines in Lewis rats. Measurable changes in Tl relaxation time suggesting widespread increase in BBB permeability were found, starting on day 3 post inoculation (p.i.), in the midbrain and brainstem of AT-EAE rats. In addition, we noted a significant decrease in Tl relaxation time before injection of a paramagnetic agent, in the cisternal cerebrospinal fluid (CSF) of diseased animals, starting on day 5 p.i. In vitro measurement of Tl in CSF containing various concentrations of albumin, IgM and glucose showed that, at physiological concentrations, a Tl decrease is mainly associated with an increase in albumin concentration. A moderate increase in BBB and blood-CSF barrier permeability was found as early as 4-8 h p.i., in rats injected with MBP-specific as in animals injected with ovalbumin-specific T cell lines, suggesting a non-specific mechanism. Experimental MRI may become a powerful tool to sequentially analyse changes in barrier dynamics, for example following pharmacological intervention.