Publication details

A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound Activated Perflutren Lipid Microspheres for Acute Ischemic Stroke



Year of publication 2008
Type Article in Periodical
Magazine / Source Stroke : a journal of cerebral circulation
MU Faculty or unit

Faculty of Medicine

Field Neurology, neurosurgery, neurosciences
Keywords microspheres; thrombolysis; stroke; occlusion; transcranial Doppler
Description Background and Purpose: Ultrasound transiently expands perflutren lipid microspheres (microspheres), transmitting energy momentum to surrounding fluids. We report a pilot safety/feasibility study of ultrasound-activated microspheres with systemic tissue plasminogen activator (tPA). Methods: Stroke subjects treated within 3 hours had abnormal Thrombolysis in Brain Ischemia (TIBI) residual flow grades 0 to 3 before tPA on transcranial Doppler (TCD). Randomization included Controls (tPA plus TCD) or Target (tPA plus TCD plus 2.8 mL microspheres). The primary safety end point was symptomatic intracranial hemorrhage (sICH) with worsening by 4 or more NIHSS points within 72 hours. Results: Fifteen subjects were randomized 3:1 to Target, n=12 or Control, n=3. After treatment, asymptomatic ICH occurred in 3 Target and 1 Control, and sICH was not seen in any study subject. Microspheres reached MCA occlusions in all Target subjects at velocities higher than surrounding residual red blood cell flow: 39.8 plus minus 11.3 vs 28.8 plus minus 13.8 cm/s,P=0.001. In 75% of subjects, microspheres permeated to areas with no pretreatment residual flow, and in 83% residual flow velocity improved at a median of 30 minutes from start of microspheres infusion (range 30 s to 120 minutes) by a median of 17 cm/s (118% above pretreatment values). To provide perspective, current study recanalization rates were compared with the tPA control arm of the CLOTBUST trial: complete recanalization 50% versus 18%, partial 33% versus 33%, none 17% versus 49%, P=0.028. At 2 hours, sustained complete recanalization was 42% versus 13%, P=0.003, and NIHSS scores 0 to 3 were reached by 17% versus 8%, P=0.456. Conclusions: Perflutren microspheres reached and permeated beyond intracranial occlusions with no increase in sICH after systemic thrombolysis suggesting feasibility of further microspheres dose escalation studies and development of drug delivery to tissues with compromised perfusion.

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