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(Stroke. 2008;39:1476.)
© 2008 American Heart Association, Inc.

Original Contributions

Quantification of Microspheres Appearance in Brain Vessels

Implications for Residual Flow Velocity Measurements, Dose Calculations, and Potential Drug Delivery

Vijay K. Sharma, MD; Georgios Tsivgoulis, MD; Annabelle Y. Lao, MD; Marc D. Malkoff, MD; Anne W. Alexandrov, PhD Andrei V. Alexandrov, MD

From the Comprehensive Stroke Center (V.K.S., G.T., A.W.A., A.V.A.), University of Alabama at Birmingham; the National University Hospital (V.K.S.), Singapore; the Department of Neurology (G.T.), Eginition Hospital, University of Athens, Greece; and the Stroke and Critical Care Program (A.Y.L., M.D.M.), Barrow Neurological Institute, Phoenix, Ariz.

Correspondence to Dr Andrei V. Alexandrov, UAB Comprehensive Stroke Center, RWUH M226, 619 19th St South, Birmingham, AL 35249-3280. E-mail avalexandrov{at}att.net

Background and Purpose— Characteristics of ultrasound-activated gaseous microspheres (µS) reflective of their size and quantities are needed for future dose-escalation and drug delivery trials.

Methods— A double-blind, interobserver-validated analysis of multi-gate power-motion Doppler µS traces included large (>8µ) µS from agitated saline injections in the right-to-left shunt (RLS) positive stroke patients and small (<5µ) µS from acute patients without shunts receiving thrombolysis and perflutren-lipid µS.

Results— In 101 µS traces from 50 RLS-positive and 10 thrombolysis+µS treated patients, a large µS passage had median maximum duration 30.8 ms (interquartile range [IQR] 22.0ms), multi-gate travel time (MGTT) 58.6±19.3 ms versus small µS: duration 8.3ms (IQR 4.3ms), MGTT 43.2±13.9ms, P<0.001. Small µS had higher embolus-to-blood ratio (EBR): 17.5 (IQR 9.3) versus 7.5 (IQR 4), P<0.001. Receiver-operating curve areas were: duration 0.989 (95% CI 0.968 to 1.000), MGTT 0.766 (0.672 to 0.859), and EBR (Embolus-to-Blood Ratio) 0.927 (0.871 to 0.982), P<0.001. A 15.1-ms duration discriminated size ranges with 98% to 99% accuracy. On average, 130 sequential large (range 51 to 260) and 500 (265–588) small µS can produce continuous flow enhancement for 4 seconds. Small µS velocities on m-mode in obstructed vessels (39.8±11.3 cm/s) were similar to large µS in patent vessels (40.8±11.5 cm/s; P=0.719) and higher than surrounding red blood cell velocities (28.8±13.8 cm/s, P<0.001).

Conclusions— With normal or reduced flow, activated µS passage duration through a small power motion Doppler gate can quantify the dose of delivered µS. Ultrasound can determine a minimum number of µS needed to achieve constant flow enhancement and targeted drug delivery. Propagation speed of µS smaller than red blood cells may reflect plasma flow velocities around acute occlusions.

Key Words: microspheres • stroke • occlusion • transcranial Doppler

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				A. V. Alexandrov, R. Mikulik, M. Ribo, V. K. Sharma, A. Y. Lao, G. Tsivgoulis, R. M. Sugg, A. Barreto, P. Sierzenski, M. D. Malkoff, et al. A Pilot Randomized Clinical Safety Study of Sonothrombolysis Augmentation With Ultrasound-Activated Perflutren-Lipid Microspheres for Acute Ischemic Stroke Stroke, May 1, 2008; 39(5): 1464 - 1469. [Abstract] [Full Text] [PDF]