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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 agentIn 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.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.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.