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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

Characteristic	Control	Active
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

Field	US+MB	r-tPA	US+MB+r-tPA	Ultrasound alone	Control
Intervention	Ultrasound (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 microbubbles	No active treatment
Duration	30 minutes	30 minutes	30 minutes	30 minutes	N/A

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Cerebral infarct volume at 24 hours (MRI/TTC)	Primary	White: 26.9%, Red: 24.6%	White: 9.5%, Red: 8.6% (US+MB)	17.40%	<0.01
Neurological score at 24h	Secondary	Score 2–3	Score 1 (US+MB)		<0.01
Recanalization of mesenteric vessels	Secondary	0%	>75% (US+MB)		<0.05
Intracerebral Hemorrhage	Adverse	0%	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)