A TRANSPULMONARY CONTRAST-MEDIUM ENHANCES THE TRANSCRANIAL DOPPLER SIGNAL IN HUMANS

Background and Purpose: Transtemporal insonation in transcranial Doppler sonography is often impaired by an insufficient signal-to-noise ratio, especially in elderly patients. A transpulmonary stable air microbubble suspension was injected intravenously in humans as an intracranial ultrasonic contrast agent. Methods: In a clinical phase II study, 20 patients (15 women, 5 men; mean age, 65.5+/-11.5 years) presenting with clinical indications for transcranial Doppler investigation were examined. A total of 97 intravenous injections with different concentrations (200,300, and 400 mg/mL of suspension) of air microbubbles bound to galactose microparticles as a carrier were performed. The signal enhancement of color-coded pulse curves of basal cerebral arteries was evaluated off-line in comparison to an integrated color-coded decibel scale, considering quality, quantity, and time course of enhancement requiring a 3-dB level above the native signal. The overall diagnostic information was assessed according to a reliability score. Results: The first acoustic signal increase was registered after an average of 21 seconds. Time intervals for a dose-dependent peak intensity and maximal duration were 41.3+/-17.1 seconds and 118.0+/-69.8 seconds (200 mg/mL); 55.5+/-27.7 seconds and 237.0+/-112.3 seconds (300 mg/mL); and 66.1+/-31.8 seconds and 293.0+/-122.0 seconds (400 mg/mL), respectively. Duration of signal enhancement increased significantly (P<.05) with higher concentrations. The extent of signal enhancement during the whole pulse curve reached an average of 9.1+/-5.0 dB for 200 mg/ml, 12.0+/-5.4 dB for 300 mg/mL (significant on P<.05 level), and 13.1+/-5.6 dB for 400 mg/mL concentration (P=NS). Respective maximal intensity spots reached 17.5+/-6.0, 20.7+/-5.5, and 22.7+/-5.9 dB for increasing concentrations, respectively. Overall visual assessment of enhanced pulse curves for diagnostic reliability showed a sufficient result in 38.1% of all injections with 200 mg/mL, in 88.6% with 300 mg/mL, and in 84.2% with 400 mg/mL concentration. Minimal side effects occurring in 12.4% of all injections were all reversible. Conclusions. Transpulmonary stable air microbubbles bound to a galactose carrier represent a useful and safe contrast agent in case of an insufficient native signal in transcranial Doppler investigation.