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 6h after a 10min 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.