Enhanced High Rate Shockwave Lithotripsy in an in vivo Porcine Model Using Acoustic Bubble Coalescence
The objective of this study was to improve the efficacy of shockwave lithotripsy treatments by actively stimulating bubble coalescence and dispersing pre-focal residual bubble nuclei from the propagation path in an in vivo porcine model in order to enhance high rate shockwave lithotripsy.
Shockwave lithotripsy (SWL) is a non-invasive method for the treatment of urinary stones. SWL is utilized to replace surgical removal of urinary stones. In SWL, stones are fragmented by applying acoustic energy from outside of the body. One of the main issues with the current clinical use of SWL is the incomplete fragmentation of stones. These incomplete fragments can cause extreme pain when they are discarded. They can also act as nidus for additional stone formation.
In SWL treatments, mechanical stresses of incident shockwave and the collapse of cavitation bubble cloud on the surface of the stone are the main causes of stone fragmentation. Cavitation bubbles are formed by the tensile portion of the lithotripsy waveform and typically have a lifespan of about 1 ms, which is much shorter than the time interval between consequent shockwaves in lithotripsy with typical firing rates rage of 0.5-2 Hz. However, the residual micron sized bubbles following a cavitation cloud collapse have a longer lifespan on the order of 1 second, and thus are expected to persist between subsequent shockwaves particularly at higher firing rates. At low firing rates, there is sufficient time for a majority of the bubbles to passively dissolve, while at high firing rates, efficacy is significantly reduced due to persisting bubbles. On subsequent shocks, these nuclei along the propagation path may attenuate subsequent shockwave, and particularly absorb energy from the negative pressure phase of the lithotripter waveform, reducing cavitation on the surface of the stone, which in turn reduces the efficacy of treatment in producing fine fragments.
In our previous studies, low amplitude acoustic bursts were used with in vitro models to actively remove residual cavitation bubbles through forced coalescence. Significant improvement was demonstrated in the comminution efficacy of SWL at higher rates (120 and 60 SW/min). In this study, the feasibility of SWL stone comminution at 120 SW/min with acoustic bubble coalescence (ABC) was evaluated on a porcine model and compared to standard SWL at the same rate.
In Vivo Experiments
A total of twelve 45 to 50 kg female pigs were used in this study. Model stones were percutaneously implanted into the mid or lower pole of the right kidney of each of the subjects.
A stereotactic positioning setup was used where a curvilinear imaging array probe was positioned with a 3-axis motorized system to target the implanted stone. The imaging probe assembly was then removed and replaced with the lithotripter head assembly where the focus was aligned to the ultrasound image.
The animal’s vital signs including oxygen saturation, heart rate, respiration and core body temperature were monitored throughout the experiment.
A laboratory electro-hydraulic lithotripter (EHL) was used for all the treatments. Each subject was treated with 2500 lithotripsy shockwaves at 120 SW/min with or without ABC. Acoustic bubble coalescence sequences were applied during five of the ten experiments interleaved between each shockwave. The ABC transducer was constructed in-house, consisting of an annular array of eight 500 kHz transducers each 50 mm diameter surrounding the lithotripter reflector. ABC sequences consisted of alternating tone bursts of 2 cycles from each transducer at a PRF of 100 kHz and amplitude of 1 MPa for a total duration of 16 ms.
Acoustic Pulse Sequence generated by laboratory electro-hydraulic lithotripter and ABC array transducer
Post-treatment position of the targeted kidney stone was confirmed by removing the lithotripter head and reattaching the ultrasound imaging probe assembly. The subject was then euthanized and the kidney was harvested, sectioned, and all the stone fragments remaining in the collecting system were recovered and sorted through a set of mesh filters.
Comparing the results of stone comminution, a significant improvement was observed in the stone fragmentation process when ABC was used.
All SWL only treatments had at least one remaining fragment larger than 4 mm averaging 65% of the initial stone mass, when only one of five treatments using SWL with ABC had any remnant fragment larger than 4 mm. Looking at a smaller size threshold, the normal SWL treatment left behind on average 75% of the stone mass in fragments larger than 2 mm, while the SWL treatment combined with ABC left on average only 25% of the mass larger than 2 mm (T-Test, p-value = 0.003)
Typical results from normal SWL treatment (a, c) and SWL with ABC (b, d). Recovered fragments from treatments with normal SWL (c) were visibly larger than treatments with SWL and ABC (d).
Post-treatment stone fragment distribution normalized to initial stone mass for normal SWL and SWL combined with ABC. The distribution is significantly shifted toward smaller fragments for SWL with ABC.
This study demonstrates the feasibility of utilizing acoustic bubble coalescence in enhancing higher rate shockwave lithotripsy in an in vivo model. A comparison of the results of stone comminution, suggests significant improvement in the stone fragmentation process when ABC were applied. Complete comminution was increased from average of %25 to %75 of the initial mass when SWL was used with ABC. These results suggest that acoustic bubble coalescence can mitigate the shielding effect of residual cavitation bubbles resulting in a more efficient SWL treatment.
An additional problem with higher rate SWL is increased risk for collateral tissue damage. Cavitation within the kidney parenchyma is thought to be the source of this damage. It is possible that ABC with SWL could help reduce this damage by preventing a proliferation of cavitation bubbles expanding into the kidney tissue. Moreover, SWL enhanced with ABC requires smaller dose of shockwaves for the same result, which could result in lower amount of tissue damage.
Alavi Tamaddoni, W. W. Roberts, A. P. Duryea, C. A. Cain, and T. L. Hall, “Enhanced High-Rate Shockwave Lithotripsy