Development of a burst wave lithotripsy system for noninvasive fragmentation of ureteroliths in pet cats

Abstract

Background: Upper urinary tract stones are increasingly prevalent in pet cats and are difficult to manage. Surgical procedures to address obstructing ureteroliths have short- and long-term complications, and medical therapies (e.g., fluid diuresis and smooth muscle relaxants) are infrequently effective. Burst wave lithotripsy is a non-invasive, ultrasound-guided, handheld focused ultrasound technology to disintegrate urinary stones, which is now undergoing human clinical trials in awake unanesthetized subjects.

Results: In this study, we designed and performed in vitro testing of a modified burst wave lithotripsy system to noninvasively fragment stones in cats. The design accounted for differences in anatomic scale, acoustic window, skin-to-stone depth, and stone size. Prototypes were fabricated and tested in a benchtop model using 35 natural calcium oxalate monohydrate stones from cats. In an initial experiment, burst wave lithotripsy was performed using peak ultrasound pressures of 7.3 (n = 10), 8.0 (n = 5), or 8.9 MPa (n = 10) for up to 30 min. Fourteen of 25 stones fragmented to < 1 mm within the 30 min. In a second experiment, burst wave lithotripsy was performed using a second transducer and peak ultrasound pressure of 8.0 MPa (n = 10) for up to 50 min. In the second experiment, 9 of 10 stones fragmented to < 1 mm within the 50 min. Across both experiments, an average of 73-97% of stone mass could be reduced to fragments < 1 mm. A third experiment found negligible injury with in vivo exposure of kidneys and ureters in a porcine animal model.

Conclusions: These data support further evaluation of burst wave lithotripsy as a noninvasive intervention for obstructing ureteroliths in cats.

Fig. 1

A Three-dimensional anatomic surface models derived from CT data, showing the urinary tract, bone structure, and intestinal tract in a cat. B Surface rendering of the skin, with green points indicating center positions of a 5-cm diameter transducer with a clear acoustic window to the left kidney, left proximal ureter, and urethra (top to bottom). The pink-yellow scale indicates the skin-to-stone depth at different points along the surface with a clear acoustic path to the stone

Fig. 2

A Simulated ultrasound pressure field for the designed burst wave lithotripsy transducer. The pressure value corresponds to the relative pressure between the focus and surface of the transducer. B Cross sectional diagram of the transducer design, containing the piezoelectric element, acoustic lens, and off-axis ultrasound imaging transducer for therapy monitoring

Fig. 3

Design of a burst wave lithotripsy system for fragmentation of feline ureteroliths. A The fabricated transducer and pulse generator with power supply. B Close-up of the transducer applicating surface, using a rubber membrane covering filled with water between the membrane and transducer for flexible contact with the skin

Fig. 4

Example of a feline calcium oxalate urolith before (left) and after (right) 10 min of burst wave lithotripsy at 8.0 MPa pressure amplitude

Fig. 5

Boxplots showing the percentage of the mass of a stone fragmented to < 1 mm as a function of focal pressure and transducer for burst wave lithotripsy exposures up to 30 min. The black circles are individual data points for each stone. TX1 indicates the first transducer/experiment and TX2 indicates the second transducer/experiment

Fig. 6

Proportion of stones completely fragmented to < 1 mm pieces as a function of total exposure time in the four treatment groups across two experiments. TX1 indicates the first transducer/experiment and TX2 indicates the second transducer/experiment

Fig. 7

A Localized bleeding in renal cortex. Total damage extends approximately 200 µm × 100 µm and is consistent with mechanical trauma due to ultrasound. B Partial dissection of the inner layer of the ureter approximately 200 µm thick. This may be from the ultrasound exposure, but the lack of any bleeding is inconsistent with previously observed injury in vivo. It may also be from stone implantation or extraction during necropsy, or histologic processing artifacts. C Focal damage and localized denudation of urothelium. Focal damage is ≤ 400 µm from the urothelial surface. Stone fragments (black) are evident in the lumen. Again, the lack of bleeding is inconsistent with previously observed mechanical injury due to ultrasound exposure. Effects are potentially from stone implantation or histologic processing artifacts