Phase I: transcranial echo contrast studies in healthy volunteers.
OBJECTIVE
Transcranial ultrasound diagnostics are particularly hindered by insufficient ultrasound penetration through the temporal bone. The use of ultrasonic contrast media to enhance the Doppler signal is an important step toward the solution of this problem. In the present study we investigated the tolerability and the diagnostic value of a new intravenous transpulmonary ultrasonic contrast medium, BY963.


METHODS
In two phase I studies, 8 healthy volunteers received a spherosome suspension containing a phospholipid as the active ingredient. The intravenous injection was performed in three doses (2.5, 5, and 10 mL) at four different injection rates (0.25, 0.5, and 1 mL/s and bolus). The duration and degree of the signal enhancement were measured by two transcranial ultrasonic procedures presently used in clinical practice: transcranial Doppler sonography (TCD) and transcranial color-coded sonography (TCCS). The assessment of tolerability was based on chemical laboratory parameters and hemodynamic data (heart rate, blood pressure, electrocardiogram) and on questionnaires relating to general well-being.


RESULTS
BY963 was tolerated without complications. All 38 administrations of the echo contrast medium produced a marked increase in the TCD signal (> 30 dB) in the intracranial basal cerebral arteries. To obtain the optimum time window for diagnostic use, higher doses with slower injection rates are advantageous. The duration of optimal contrasting was 42 to 68 seconds (TCD) and 12 to 132 seconds (TCCS), depending on the method and mode of administration. Bolus injections gave rise to an increased incidence of color artifacts.


CONCLUSIONS
BY963 significantly improves intracranial Doppler imaging while being well tolerated. The signal enhancement lasts long enough for TCCS to display all basal cerebral arteries after just one injection.
D000328:Adult; D003287:Contrast Media / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D012680:Sensitivity and Specificity; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods*
C096494:BY 963; D003287:Contrast Media; D010713:Phosphatidylcholines