Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jul;46(7):419-24.
doi: 10.1097/RLI.0b013e31820e143a.

Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke

Rene Flores  1 , Leah J Hennings, John D Lowery, Aliza T Brown, William C Culp
Affiliations

Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke

Rene Flores et al. Invest Radiol. 2011 Jul.

Abstract

Objectives: Increasing evidence confirms that microbubble (MB)-augmented ultrasound (US) thrombolysis enhances clot lysis with or without tissue plasminogen activator (tPA). Intracranial hemorrhage (ICH) is a major complication militating against tPA use in acute ischemic stroke. We quantified the incidence of ICH associated with tPA thrombolysis and MB + US therapy and compared infarct volumes in a rabbit model of acute ischemic stroke.

Materials and methods: Rabbits (n = 158) received a 1.0-mm clot, angiographically injected into the internal carotid artery causing infarcts. Rabbits were randomized to 6 test groups including (1) control (n = 50), embolized without therapy, (2) US (n = 18), (3) tPA only (n = 27), (4) tPA + US (n = 22), (5) MB + US (n = 27), and (6) tPA + MB + US (n = 14). US groups received pulsed wave US (1 MHz, 0.8 W/cm) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Rabbits with MB received intravenous MB (0.16 mg/kg) given over 30 minutes. Rabbits were killed 24 hours later and infarct volume and incidence, location, and severity of ICH were determined by histology and pathologic examination.

Results: Percentage of rabbits having ICH outside the infarct area was significantly decreased (P = 0.004) for MB + US (19%) rabbits compared with tPA + US (73%), US only (56%), tPA (48%), tPA + MB + US (36%), and control (36%) rabbits. Incidence and severity of ICH within the infarct did not differ (P > 0.39). Infarct volume was significantly greater (P = 0.002) for rabbits receiving US (0.97% ± 0.17%) than for MB + US (0.20% ± 0.14%), tPA + US (0.15% ± 0.16%), tPA (0.14% ± 0.14%), and tPA + MB + US (0.10% ± 20%) rabbits; these treatments collectively, excluding US only, differed (P = 0.03) from control (0.45% ± 0.10%).

Conclusions: Treatment with MB + US after embolization decreased the incidence of ICH and efficacy was similar to tPA in reducing infarct volume.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest/Disclosures: None

Figures

Figure 1
Figure 1
Cerebral angiogram showing complete filling of a middle cerebral artery (MCA) prior to embolization (A). Subtracted angiogram one minute following embolization shows MCA occlusion (arrow) (B).
Figure 2
Figure 2
TTC-stained brain section showing infarction (arrow).
Figure 3
Figure 3
Histopathological sections, stained with hematoxylin and eosin (H&E), of the rabbit brain showing hemorrhage within infarct (A) and outside infarct (B).
Figure 4
Figure 4
Histopathological sections of the rabbit brain showing hemorrhage following H&E staining. A hemorrhage severity score ranging from 0 (no hemorrhage) to 4 (severe hemorrhage) was assigned to each H&E-stained section. A and B are grade 1; C and D grade 2; and E and F grade 3.
See this image and copyright information in PMC

References

    1. Molina CA, Ribo M, Rubiera M, et al. Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke. 2006;37:425–429. - PubMed
    1. Alexandrov AV, Mikulik R, Ribo M, et al. A pilot randomized clinical safety study of sonothrombolysis augmentation with ultrasound-activated perflutren-lipid microspheres for acute ischemic stroke. Stroke. 2008;39:1464–1469. - PMC - PubMed
    1. Perren F, Loulidi J, Poglia D, et al. Microbubble potentiated transcranial duplex ultrasound enhances IV thrombolysis in acute stroke. J Thromb Thrombolysis. 2008;25:219–223. - PubMed
    1. Porter TR, Kricsfeld D, Lof J, et al. Effectiveness of transcranial and transthoracic ultrasound and microbubbles in dissolving intravascular thrombi. J Ultrasound Med. 2001;20:1313–1325. - PubMed
    1. Culp WC, Erdem E, Roberson PK, et al. Microbubble potentiated ultrasound as a method of stroke therapy in a pig model: preliminary findings. J Vasc Interv Radiol. 2003;14:1433–1436. - PubMed

Publication types

Substances