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Microbubble

Microbubble-Mediated Sonothrombolysis Improves Outcome After Thrombotic Microembolism–Induced Acute Ischemic Stroke

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Year of Publication: 2016

Authors: Yongkang Lu, Junfen Wang, Ruizhu Huang, ..., Jianping Bin

Journal: Stroke

Citation: Stroke. 2016;47:1344–1353. doi:10.1161/STROKEAHA.115.012056

Link: https://www.ahajournals.org/doi/10.1161/STROKEAHA.115.012056

PDF: https://www.ahajournals.org/doi/reader/1...EAHA.115.012056

Clinical Question

Can microbubble-mediated sonothrombolysis improve outcomes after microthrombi-induced acute ischemic stroke?

Bottom Line

Microbubble-mediated sonothrombolysis significantly reduced infarct volume and improved neurologic function in rat stroke models without increasing hemorrhagic risk.

Major Points

  • Rats with embolic stroke from microthrombi were treated with combinations of ultrasound, microbubbles, and r-tPA
  • US+MB therapy was effective for both platelet-rich and erythrocyte-rich microthrombi
  • Infarct volumes and neurological deficits were significantly reduced with US+MB compared to control or r-tPA alone
  • No intracerebral hemorrhage was observed after US+MB treatment
  • Platelet-rich thrombi were resistant to r-tPA but responsive to US+MB

Design

Study Type: Preclinical, in vivo rat stroke model

Randomization: 1

Blinding: Blinded outcome assessment

Enrollment Period: Not applicable (animal model)

Follow-up Duration: 24 hours post-stroke

Centers: 1

Countries: China

Sample Size: 125

Analysis: ANOVA, Kruskal–Wallis, Fisher exact test, blinded observers

Inclusion Criteria

  • Male Sprague–Dawley rats
  • Induced mesenteric thrombosis or embolic cerebral ischemia from microthrombi
  • 70–100 μm thrombi derived from platelet-rich or erythrocyte-rich clots

Exclusion Criteria

  • None reported (animal model)

Baseline Characteristics

CharacteristicControlActive
Neurological Score (24h)2–3
Infarct Volume (White Thrombi, MRI)26.9 ± 3.1%9.5 ± 3.0%
Infarct Volume (Red Thrombi, MRI)24.6 ± 3.1%8.6 ± 2.8%
Neurological Score (24h, US+MB)1

Arms

FieldUS+MBr-tPAUS+MB+r-tPAUltrasound aloneControl
InterventionUltrasound (2 MHz, 30 min) + IV microbubbles (0.008 mL/min)10 mg/kg IV r-tPA (bolus + 30-min infusion)Ultrasound + IV microbubbles + half-dose r-tPA (5 mg/kg)Ultrasound (2 MHz, 30 min) without microbubblesNo active treatment
Duration30 minutes30 minutes30 minutes30 minutesN/A

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Cerebral infarct volume at 24 hours (MRI/TTC)PrimaryWhite: 26.9%, Red: 24.6%White: 9.5%, Red: 8.6% (US+MB)17.40%<0.01
Neurological score at 24hSecondaryScore 2–3Score 1 (US+MB)<0.01
Recanalization of mesenteric vesselsSecondary0%>75% (US+MB)<0.05
Intracerebral HemorrhageAdverse0%0%NS

Subgroup Analysis

US+MB was effective in both platelet-rich and erythrocyte-rich microthrombi; r-tPA alone was ineffective for platelet-rich microthrombi

Criticisms

  • Animal study — findings may not translate directly to humans
  • Short 24-hour follow-up period; late hemorrhage not assessed
  • Used only fresh thrombi — older thrombi may behave differently

Funding

National Basic Research Program of China, National Natural Science Foundation of China, Guangdong Province Team Program

Based on: Microbubble (Stroke, 2016)

Authors: Yongkang Lu, Junfen Wang, Ruizhu Huang, ..., Jianping Bin

Citation: Stroke. 2016;47:1344–1353. doi:10.1161/STROKEAHA.115.012056

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