Intrahematomal Ultrasound Enhances RtPA-Fibrinolysis in a Porcine Model of Intracerebral Hemorrhage

Abstract

Catheter-based ultrasound-thrombolysis has been successfully used in a small clinical trial in order to enhance recombinant tissue plasminogen activator (rtPA)-fibrinolysis, for the treatment of spontaneous intracerebral hemorrhages (ICHs). The aim of this study was to investigate the ultra-early effects of ultrasound on hematoma and the surrounding brain tissue in a porcine ICH-model. To achieve this, 21 pigs with a right frontal ICH were randomly assigned to four groups: (1) drainage (n = 3), (2) drainage + rtPA (n = 6), (3) drainage + ultrasound (n = 6), and (4) drainage + ultrasound + rtPA (n = 6). The hematoma volume assessment was performed using cranial MRI before and after the treatments. Subsequently, the brain sections were analyzed using HE-staining and immunohistochemistry. The combined treatment using rtPA and ultrasound led to a significantly higher hematoma reduction (62 ± 5%) compared to the other groups (Group 1: 2 ± 1%; Group 2: 30 ± 12%; Group 3: 18 ± 8% (p < 0.0001)). In all groups, the MRI revealed an increase in diffusion restriction but neither hyper- or hypoperfusion, nor perihematomal edema. HE stains showed perihematomal microhemorrhages were equally distributed in each group, while edema was more pronounced within the control group. Immunohistochemistry did not reveal any ultra-early side effects. The combined therapy of drainage, rtPA and ultrasound is a safe and effective technique for hematoma-reduction and protection of the perihematomal tissue in regard to ultra-early effects.

A minimally invasive strategy to evacuate hematoma by synergy of an improved ultrasonic horn with urokinase: An in vitro study

“…Mechanical effects, including radiation force, acoustic streaming, and acoustic cavitation are proposed to be the primary mechanisms 20 . Compared to traditional extra‐lesion ultrasonic irradiation therapies, 16,21–23 intra‐lesion ultrasonic irradiation therapies will not be restricted by acoustic windows (e.g., ultrasound beam blocking by skull), 21 and can directly target to the treatment area, avoiding ultrasonic effect on non‐target areas 18,24 . In addition, therapeutic ultrasonic energy of intra‐lesion irradiation can be reliably calculated with less influence by the acoustic attenuation in different biological tissues compared with the process of extra‐lesion irradiation 25 .…”

“…20 Compared to traditional extra-lesion ultrasonic irradia-tion therapies, 16,[21][22][23] intra-lesion ultrasonic irradiation therapies will not be restricted by acoustic windows (e.g., ultrasound beam blocking by skull), 21 and can directly target to the treatment area, avoiding ultrasonic effect on non-target areas. 18,24 In addition, therapeutic ultrasonic energy of intra-lesion irradiation can be reliably calculated with less influence by the acoustic attenuation in different biological tissues compared with the process of extra-lesion irradiation. 25 At present, most of the studies on ultrasound thrombolytic therapy focus on the treatment of intravascular thrombosis, 15,16 and few ultrasound strategies are applied to the treatment of intracranial hematoma.…”