Quantification of microspheres appearance in brain vessels: implications for residual flow velocity measurements, dose calculations, and potential drug delivery.

BACKGROUND AND PURPOSE Characteristics of ultrasound-activated gaseous microspheres (muS) 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 microS traces included large (>8 micro) microS from agitated saline injections in the right-to-left shunt (RLS) positive stroke patients and small (<5 micro) microS from acute patients without shunts receiving thrombolysis and perflutren-lipid microS. RESULTS In 101 microS traces from 50 RLS-positive and 10 thrombolysis+microS treated patients, a large microS passage had median maximum duration 30.8 ms (interquartile range [IQR] 22.0 ms), multi-gate travel time (MGTT) 58.6+/-19.3 ms versus small microS: duration 8.3 ms (IQR 4.3 ms), MGTT 43.2+/-13.9 ms, P<0.001. Small microS 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 microS can produce continuous flow enhancement for 4 seconds. Small microS velocities on m-mode in obstructed vessels (39.8+/-11.3 cm/s) were similar to large microS 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 muS passage duration through a small power motion Doppler gate can quantify the dose of delivered microS. Ultrasound can determine a minimum number of microS needed to achieve constant flow enhancement and targeted drug delivery. Propagation speed of microS smaller than red blood cells may reflect plasma flow velocities around acute occlusions.