Rich Raspet was a dedicated researcher and teacher in the field of physical acoustics. This talk will recall a former student’s interactions with Rich and a final homework problem related to the treatment of venous clots. Improved outcomes have been observed when clot-busting thrombolytic drugs are combined with histotripsy, a focused ultrasound therapy that breaks down tissue via bubble activity. To gain insight into the mechanisms of this combination approach, an in silico model of bubble/thrombolytic/clot interaction was developed. The methods to calculate bubble dynamics and drug/clot interaction were known, but additional insights were needed to model delivery of the drug. After many dead ends, the student reached out to his former teacher once again for guidance. Rich was able to distill the problem down to its essential elements, which led to adoption of the perfusion-diffusion equation to complete the calculation. Findings from the resultant model indicated histotripsy increases the penetration of thrombolytic drug into the clot relative to just the drug alone. These analyses were validated by in vitro measurements and suggest that the observed enhancement in drug activity was the result of histotripsy-induces changes to tissue perfusivity.
Kenneth B. Bader (Tue,) studied this question.