CONTRAST-ENHANCED TRANSCRANIAL IMAGING - RESULTS OF AN AMERICAN PHASE-2 STUDY

Background and Purpose Pulsed color Doppler imaging of cerebrovascular structures permits rapid visual identification of the intracranial vessels. In some patients, however, the clinical utility of transcranial ultrasound examinations is limited by poor tissue penetration and inadequate imaging of vessels. This phase-two clinical trial evaluates whether administration of an echocontrast agent in such ultrasound-refractory patients enhances image acquisition enough to yield meaningful diagnostic impressions. Methods This is a phase-two clinical trial of safety and efficacy of the ''galactose/palmitic acid-based microbubble preparation'' Levovist injection (Berlex Laboratories). Thirty subjects with clinical indications for cerebrovascular imaging but refractory to transcranial Doppler studies were enrolled in a nonrandomized, single-center study. Echocontrast agent was administered intravenously in a tiered-dose protocol. Safety was determined by clinical and laboratory monitoring for 18 to 24 hours. Efficacy of contrast enhancement was determined by comparisons between each patient's precontrast (control) and postcontrast images. Results No significant patient discomfort, side effects, or adverse reactions occurred that were due to-the intravenous administration of the echocontrast agent. Optimal image enhancement was obtained using the 300-mg/mL concentration (3 g bolus) of contrast. Visualization of both individual arterial segments and/or the entire circle of Willis was demonstrated. Clinical confidence of diagnostic impressions was achieved in 77% (23/30) of subjects. Conclusions The transpulmonary ultrasound contrast agent (Levovist injection) was easily administered and found to be safe in the 30 patients studied and increased the diagnostic utility of transcranial ultrasound in 77% of the patients studied.