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Published on: December 15, 2010
Treatment of microvascular micro-embolization using microbubbles and long-tone-burst ultrasound: an in vivo study
John J Pacella1, Judith Brands1, Frederick G Schnatz1
1Center for Ultrasound and Molecular Imaging and Therapeutics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Insights
Sonothrombolysis, using ultrasound and microbubbles, effectively restores blood flow in microvascular obstruction models. This technique shows promise as an adjunct therapy for acute myocardial infarction, improving tissue perfusion after percutaneous coronary intervention.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Medical Imaging
Background:
- Percutaneous coronary intervention (PCI) can lead to distal micro-embolization, impairing myocardial salvage in acute myocardial infarction (AMI).
- Microvascular obstruction following reperfusion therapy limits treatment efficacy.
- Sonothrombolysis, utilizing ultrasound-induced microbubble oscillations, offers a potential method for clot disruption and perfusion restoration.
Purpose of the Study:
- To evaluate the efficacy of sonothrombolysis in restoring impaired microvascular perfusion caused by thrombotic microvascular obstruction.
- To establish an in vivo animal model simulating distal thrombotic microvascular obstruction post-PCI.
Main Methods:
- An in vivo rat model was used to induce and assess microvascular obstruction.
- Ultrasound contrast perfusion imaging measured microvascular volume (peak video intensity) before and after interventions.
- Sonothrombolysis involved intra-arterial infusion of lipid-encapsulated microbubbles combined with therapeutic ultrasound (1 MHz, 1.5 MPa).
Main Results:
- Micro-embolization caused a significant 90% decrease in microvascular perfusion (video intensity).
- Ultrasound-microbubble therapy led to substantial increases in video intensity after both treatment sessions (5.8 ± 5.1 dB and 8.7 ± 5.7 dB, p < 0.01).
- Control groups without ultrasound-microbubble therapy showed no significant improvement in perfusion.
Conclusions:
- Long-pulse-length ultrasound with microbubbles effectively restores microvascular perfusion in a model of distal thrombotic microvascular obstruction.
- Sonothrombolysis demonstrates a therapeutic effect and may serve as a valuable adjunct to reperfusion strategies for acute myocardial infarction.
Abstract:
Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound-microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound-microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction.
