gms | German Medical Science

Objective: Catheter-based hematoma lysis with recombinant tissue plasminogen activator (rtPA) is a well-established therapy of spontaneous intracerebral hemorrhage (ICH). Randomized trials showed the effectiveness of intralesional sonothrombolysis in combination with rtPA. Previously it was shown that 1 mg rtPA combined with 1h ultrasound exposure lead to high lysis rates in an in vitro hematoma model of aged blood clots. The aim of this study was the assessment of an optimized adaptable sonothrombolysis and its possible risks using an endosonography catheter in an in vitro hematoma model.

Method: Blood clots of 25 ml human blood with 10 IE thrombin were incubated for 1.5 h at 37 C°. The solid part of the clots (replicates of 3) was weighed before and after different treatments in a 37°C water bath: Lysis was achieved by an endosonography catheter (10 F in B-mode) placed at different distances from the clot. Different frequencies were tested from 10, 8.5, 7.5, 5.5 MHz different distances to the probe (0-8 cm) (replicates of 96). A brain phantom was created consisting of 3.5 l agarose gel. Temperature was measured at 1 cm increments to 8 cm distance to probe at 10 minutes intervals up to 1 h. Acoustic peak rarefaction pressure (APRP) values were measured by a pressure transducer and related to clot lysis rate assessing a lysis threshold for every frequency and distance to probe. Image quality of different frequencies was evaluated.

Results: Ultrasound application leads to an increase of temperature of < 1 C° up to 1 cm distance to probe using a frequency of 7.5 MHz. Max temperature increase with other frequencies was less than 0.5C°. APRP shows a linear decrease with increased distance to the probe. Higher values were measured using lower frequencies. Reliable thresholds for lysis were app 400 kPa measured in an agarose brain model. Best image quality was achieved by using 7.5 and 10 MHz. Lysis was possible up to a distance of 9cm using 5.5 MHz and 8 cm using 7.5 MHz, 7 cm using 8.5 MHz, 1 cm using 10 MHz.

Conclusions: Ultrasound in combination with rtPA lysis seems to be a safe and effective therapy for ICH independent of ICH age. Best imaging could be achieved using 7.5 and 10 MHz. To the best of our knowledge this is the first time that an adaptable lysis threshold related to ICH size/ distance to probe could be assessed by frequency adjustment of high frequency ultrasound. This led to effective lysis and high quality imaging without bearing a risk for surrounding tissue.