Quantification of microspheres appearance in brain vessels

Implications for residual flow velocity measurements, dose calculations, and potential drug delivery

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1476-1481
Number of pages6
JournalStroke
Volume39
Issue number5
DOIs
StatePublished - May 1 2008

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Microspheres
perflutren
Embolism
Brain
Erythrocytes
Pharmaceutical Preparations
Stroke
Lipids
Injections

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

@article{0d2d2841122049be8a247594b5c515ba,
title = "Quantification of microspheres appearance in brain vessels: Implications for residual flow velocity measurements, dose calculations, and potential drug delivery",
abstract = "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.",
author = "Sharma, {Vijay K.} and Georgios Tsivgoulis and Lao, {Annabelle Y.} and Marc Malkoff and Anne Alexandrov and Andrei Alexandrov",
year = "2008",
month = "5",
day = "1",
doi = "10.1161/STROKEAHA.107.501593",
language = "English (US)",
volume = "39",
pages = "1476--1481",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Quantification of microspheres appearance in brain vessels

T2 - Implications for residual flow velocity measurements, dose calculations, and potential drug delivery

AU - Sharma, Vijay K.

AU - Tsivgoulis, Georgios

AU - Lao, Annabelle Y.

AU - Malkoff, Marc

AU - Alexandrov, Anne

AU - Alexandrov, Andrei

PY - 2008/5/1

Y1 - 2008/5/1

N2 - 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.

AB - 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.

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U2 - 10.1161/STROKEAHA.107.501593

DO - 10.1161/STROKEAHA.107.501593

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JO - Stroke

JF - Stroke

SN - 0039-2499

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