Contrast-enhanced transcranial and extracranial duplex sonography: Preliminary results of a multicenter phase II/III study with SonoVue (TM)

Transcranial sonography is an ultrasonographic application with real proble ms of insufficient signal to noise ratio, which make it a primary candidate for applying ultrasonographic contrast enhancing agents. Within an interna tional randomized multicenter phase II/III study, we investigated ten, pati ents with insufficient Doppler signal retrieval using transcranial and extr acranial color-coded duplex sonography to define safety, toxicity, optimal dosing, and the potential of the new ultrasound contrast agent SonoVue(TM) Patients were studied with standard color duplex systems. SonoVue(TM) was a dministered by IV bolus injection at four different doses. Efficacy paramet ers included the assessment of global quality of Doppler investigations, co lor Doppler (CD), and spectral Doppler (SD) evaluated by semiquantitative a nalysis using a four-point scale from 0 to 3 (very poor to excellent) and t he duration of clinically useful signal enhancement. In addition, CD enhanc ement, evaluated at best signal enhancement, was assessed using a five-poin t scale, from no enhancement, slight, moderate, optimal to excessive (0-4). All examinations were compared to "gold" standard imaging (magnetic resona nce imaging, digital subtraction, angiography) to evaluate diagnostic confi dence at optimum dosage. No serious adverse events were observed. Mean sign al increase over baseline in CD or SD was 2 out of 4 points. Mean time to a ppearance of contrast enhancement was 22.8 seconds (9-52 sec) at the optima l dosage. The mean duration of enhancement was 281 seconds (20-593 sec) at the optimal dosage, which was of 2.4 mi of SonoVue(TM) in nine patients. CD and SD signal enhancement (n = 20, CD + SD) was considered optimal in 12 o f 20, excessive in 1 of 20, and moderate or insufficient in 5 of 20 and 2 o f 20 cases, respectively. There was a tendency for superior improvement in CD signal enhancement. Diagnostic confidence was improved in 8 of 10 cases without false diagnostic conclusions. SonoVue(TM) has been demonstrated to be a powerful and safe echo signal enhancing agent, which significantly imp roves transcranial and extracranial ultrasound investigations and increases the confidence in diagnosis.