Qualitative assessment of thermal effects in high intensity ultrasound thrombolysis experiments

Objective High Intensity Focused Ultrasounds (HIFU) demonstrated the ability to destroy blood clots without addiction of thrombolytic drugs. However, the involved physical principles are yet unclear, thus slowing a translation to clinical application. It is agreed that thermal effects must be avoided; however it is hard to directly measure the temperature because of the dynamics of the procedures. Methods We demonstrated the possibility to break human blood clots in an in-vitro system. We used a commercial HIFU transducer (Precision Acoustics) with focus dimensions (previously mapped) of 2.2mm and 23mm (-6dB focal radius and length). Acoustic parameters were: frequency 1MHz, pulse length 450μs, duty cycle (d.c.) 10%, output power 65W, therapy duration (t.d.) 120s. Results We used long segments of porcine clots (similar acoustic properties of human thrombi but easier to produce) to evaluate the presence of thermal effects, by varying the duty cycle of the sonication protocol. The following parameters were adopted in order to maintain the same amount of delivered energy: A. d.c. 100% t.d. 20s; B. d.c. 50% t.d. 40s; C. d.c. 10% (same as thrombolysis experiments) t.d. 200s; D. d.c. 0% (control). After sonication, porcine clots were cut in correspondence of the produced lesion and were observed under a digital microscope (HiroxKH7700, magnification 20x). The following features were observed: A. evidence of necrotic tissue, surface erosion and internal holes; B. moderate necrosis and surface erosion; C. presence of surface erosion, no evidence of thermal lesions; D. homogeneous and uniform surface. Conclusions The absence of visible thermal lesions enforces the hypothesis of mechanical effects in HIFU thrombolysis. Inertial cavitation should play an important role in the phenomenon and must be detected and quantified, and possibly enhanced by microbubbles. We implemented a system which detects acoustic emission of collapsing bubbles (i.e. broadband noise at high frequencies) in order to assess the influence of this phenomenon in thrombolysis.