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Feasibility of noninvasive ureterocele puncture with histotripsy focused ultrasound therapy
Adam Maxwell, PhD1, Ryan S. Hsi, MD1, Michael R. Bailey, PhD2, Pasquale Casale, MD3, Thomas S. Lendvay, MD4.
1Department of Urology, University of Washington School of Medicine, Seattle, WA, USA, 2Applied Physics Laboratory, University of Washington, Seattle, WA, USA, 3Department of Urology, Columbia University College of Physicians and Surgeons, New York, NY, USA, 4Division of Pediatric Urology, Seattle Children's Hospital, Seattle, WA, USA.

BACKGROUND: Surgical management of ureteroceles is often required to relieve urinary obstruction and preserve renal function. While treatment has progressed towards minimally-invasive procedures such as endoscopic puncture, noninvasive options are currently unavailable. This study investigated the feasibility of using cavitation-based focused ultrasound (histotripsy) to perform noninvasive puncture of ureteroceles.
METHODS: A model for the ureterocele wall was created from the mucosal membrane separated from the underlying muscular layer of fresh bovine bladder. The membrane was attached to a fixture in a bath of degassed, deionized water. A 1-MHz focused ultrasound transducer was positioned facing the sample, with the focal volume aligned to the membrane surface. The sample was exposed to ultrasound pulses with a peak positive pressure of 100-120 MPa and peak negative pressure of 17-20 MPa. Treatment was administered for a maximum of 300 seconds or until a visible puncture was created in the membrane. The duration of exposure and puncture size were recorded for each experiment. A Verasonics ultrasound imaging system with L7-4 linear array probe was used during exposures to assess the image guidance and feedback for the procedure.
RESULTS: The targeted region of the membrane was eroded and punctured after 50-300 seconds of ultrasound exposure, with the puncture time being dependent on ultrasound pulse parameters and membrane thickness. The resulting hole diameters also varied with pulse parameters from 0.5 - 3 mm, but were consistent between identical acoustic exposures (n=6-12). No erosion of the membrane was observed outside of the transducer focal zone. The cavitation bubbles generated by the therapy were visible on B-mode ultrasound imaging as a dynamic, echogenic region on the membrane surface, providing precise targeting of the sample wall. Upon puncture, imaging showed the cavitation flowing through the membrane, indicating treatment completion.
CONCLUSIONS: Histotripsy controllably generated punctures in a tissue similar to the ureterocele wall. Results suggest B-Mode ultrasound imaging can be used for real-time assessment of targeting and treatment progression. This method may provide a noninvasive alternative to endoscopic ureterocele puncture, and could potentially be applied to other instances of obstructive uropathy, such as posterior urethral valves. Work supported by NIH 2T32DK007779-11A1 and 2R01EB007643-05.


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