Diffusion into rat brain of contrast and shift reagents for magnetic resonance imaging and spectroscopy

A sensitive radiotracer technique was used to measure transfer constants (Kis) for blood to brain diffusion of the MR contrast reagent gadolinium diethylenetriaminepentaacetate (GdDTPA2-) and the MR shift reagent dysprosium triethylenetetraminehexaacetate (DyTTHA3-) across the normal and the ischemically injured blood-brain barrier (BBB) of rats. In rats with a normal BBB mean Kis (nL/g/s) for these reagents ranged from 0.3 to 1.4 across eight brain regions and were significantly lower in each region than Kis for sucrose (1.5-3.2), a substance known to be a poor permeant of the intact BBB. Kis 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 and 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 Kis of 25-30 in forebrain regions. Estimates of reagent concentrations in brain interstitial fluid 30 min after dosing the animals indicated that both an extremely high dose of DyTTHA3- and severe disruption of the BBB would be required to shift the resonance frequency of extracellular Na+ appreciably. With 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 mmol/kg would be required to quantify the injury by dynamic MRI.