gms | German Medical Science

Objective: Several studies have demonstrated the potential of transcranial Doppler with common 2 MHz probes (TCD) to enhance intravascular fibrinolysis through sonothrombolysis in ischemic stroke. Other studies have shown that catheter-based administration of rtPA induces lysis of the hematoma and reduces blood clot size in patients with intracerebral hemorrhage (ICH). However, the effect of TCD-induced sonothrombolysis has not been investigated in ICH. The aim of this study was to investigate possible fibrinolytic effects of Doppler-sonography in an established in vitro model of ICH. Furthermore we examined whether insonation with 2 TCD probes placed vis-à-vis enhances the effect of sonothrombolysis.

Methods: Experiments were performed with standardized human blood clots of 25 ml in a water bath at 37°C. A silicone catheter for drug administration and drainage was placed in the clot core. Clot weight was assessed before and after 60 min treatment in the water bath. To assess acoustic peak rarefaction pressure (APRP) a brain phantom was created consisting of 3.5 l agarose gel. Temperature and APRP were measured in the field of view of a single and of both probes. APRP measurement was also performed through a temporal squama to simulate the situation in vivo. We investigated rtPA- and TCD-induced lysis in 6 groups (each n=6): (i) 1 TCD probe, (ii) 1 mg rtPA, (iii) combination of 1 TCD probe and 1 mg rtPA, (iv) 2 TCD probes placed vis-à-vis, (v) combination of 2 TCD probes and 1 mg rtPA, and (vi) control group.

Results: Clot weight was reduced in all groups after treatment in the water bath. The control group had a relative end weight of 71.43±6.23%. Weight reduction was significantly enhanced in clots treated with 1 TCD probe (relative weight: 55.2±3.42%) or with rtPA (52.59±5.56%) compared to the control group (p<0.0001). Combination of 1 TCD probe and rtPA as well as insonation with 2 TCD probes induced a further significant weight reduction (relative weight: 46.1±4.67%; 45.09±4.26%; p<0,0001) compared to control. Most efficient clot lysis was achieved using 2 TCD probes and rtPA (36.31±4.42; p<0,0001). Application of 1 TCD probe leads to an APRP of 1609±112.6 kPA, while 2 probes showed a significantly higher APRP value (3113±173.3 kPA p<0.0001). Application through bone leads to an APRP attenuation by 70% (443.7±22.07kPA), 2 probes through bone significantly increased APRP values to 731.6±79.55 kPA, which is significant above lysis threshold.

Conclusion: TCD-induced sonothrombolysis significantly enhances rtPA-induced lysis of blood clots, and the effect of TCD-induced sonothrombolysis is amplified by using multiple TCD probes. Our results indicate that bitemporal insonation of the hematoma using image-guided 2 MHz TCD probes could be a new promising approach to enhance fibrinolysis and hematoma reduction respectively of ICH´s treated with intralesional catheter and rtPA application.