DIFFUSION INTO RAT-BRAIN OF CONTRAST AND SHIFT-REAGENTS FOR MAGNETIC-RESONANCE-IMAGING AND SPECTROSCOPY

A sensitive radiotracer technique was used to measure transfer constan ts (K(i)s) for blood to brain diffusion of the MR contrast reagent gad olinium diethylenetriaminepentaacetate (GdDTPA2-) and the MR shift rea gent dysprosium triethylenetetraminehexaacetate (DyTTHA3-) across the normal and the ischemically injured blood-brain barrier (BBB) of rats. In rats with a normal BBB mean K(i)s (nL/g/s) for these reagents rang ed from 0.3 to 1.4 across eight brain regions and were significantly l ower in each region than K(i)s for sucrose (1.5-3.2), a substance know n to be a poor permeant of the intact BBB. K(i)s measured 6 h after a 10 min period of normothermic forebrain ischemia were increased to 4.0 -6.2 (reagents) and 6.6-7.5 (sucrose) in two brain regions, striatum a nd hippocampus, known to be especially vulnerable to ischemic injury. Measurements of BBB permeability to DyTTHA3- after osmotic opening of the barrier with hypertonic arabinose gave K(i)s of 25-30 in forebrain regions. Estimates of reagent concentrations in brain interstitial fl uid 30 min after dosing the animals indicated that both an extremely h igh dose of DyTTHA3- and severe disruption of the BBB would be require d to shift the resonance frequency of extracellular Na+ appreciably. W ith the moderate degrees of BBB injury produced by short-term ischemia , a dose of GdDTPA2- about 25 times the usual clinical dose of 0.1 mmo l/kg would be required to quantify the injury by dynamic MRI.