Application unit for the administration of contrast gases for pulmonary magnetic resonance imaging: optimization of ventilation distribution for (3) He-MRI.

PURPOSE: MRI of lung airspaces using gases with MR-active nuclei ((3) He, (129) Xe, and (19) F) is an important area of research in pulmonary imaging. The volume-controlled administration of gas mixtures is important for obtaining quantitative information from MR images. State-of-the-art gas administration using plastic bags (PBs) does not allow for a precise determination of both the volume and timing of a (3) He bolus. METHODS: A novel application unit (AU) was built according to the requirements of the German medical devices law. Integrated spirometers enable the monitoring of the inhaled gas flow. The device is particularly suited for hyperpolarized (HP) gases (e.g., storage and administration with minimal HP losses). The setup was tested in a clinical trial (n = 10 healthy volunteers) according to the German medicinal products law using static and dynamic ventilation HP-(3) He MRI. RESULTS: The required specifications for the AU were successfully realized. Compared to PB-administration, better reproducibility of gas intrapulmonary distribution was observed when using the AU for both static and dynamic ventilation imaging. CONCLUSION: The new AU meets the special requirements for HP gases, which are storage and administration with minimal losses. Our data suggest that gas AU-administration is superior to manual modes for determining the key parameters of dynamic ventilation measurements.

Preclinical toxicology and safety pharmacology of brodimoprim in comparison to trimethoprim and analogs.

The toxicology and safety pharmacology of brodimoprim (Ro 10-5970), a new dihydrofolate reductase inhibitor for antimicrobial chemotherapy, are reported. The toxicity is compared to trimethoprim and other dihydrofolate reductase inhibitors of the trimethoprim type. In safety pharmacological tests brodimoprim showed no significant activity in the cardiovascular, autonomic neuroeffector or central nervous systems. Effects on urine volume and sodium and potassium excretion were not noted. The acute toxicity of brodimoprim after oral administration is low. In repeated dose studies in rats, oral doses up to 50 mg/kg/day were generally well tolerated. In the baboon no toxic effects were seen even at repeated doses up to 150 mg/kg/day; on the other hand the dog was found to be particularly sensitive to treatment as 20 mg/kg/day were poorly tolerated. Target organ systems included central nervous system, liver, red blood cell parameters and thyroid gland. Doses up to 100 mg/kg/day were not teratogenic or embryotoxic in rabbits. However, treatment with 100 mg/kg/day in reproductive toxicity studies in rats induced effects on fetal/litter weight, survival of offspring and litter size and increased the incidence of skeletal variations and malformed offspring. No mutagenicity was found in the tests performed with brodimoprim. In comparison brodimoprim shows the typical toxicity known for trimethoprim and analogs. In pyrimethamine toxic effects occurred at considerably lower doses than in the other compared compounds.