Kisting AL. et al., 2025: Histotripsy of the Proximal Ureter and Renal Pelvis: Evaluation of Urothelial Injury in a Porcine Survival Model.
Adrienne L Kisting 1, Annie M Zlevor 1, Katrina L Falk 2, Meridith A Kisting 1, Israa A Laklouk 3, Martin G Wagner 4, Jim K White 1, J Erik Winterholler 1, Madeline S Jentink 1, E Jason Abel 5, Erica M Knavel Koepsel 1, J Louis Hinshaw 6, John F Swietlik 1, Lu Mao 7, Grace M Minesinger 8, Paul F Laeseke 2, Timothy J Ziemlewicz 1, Fred T Lee Jr 9
1Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
2Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
3Department of Anatomic Pathology, University of California, Los Angeles, Los Angeles, California.
4Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin; Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.
5Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin.
6Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin; Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin.
7Department of Biostatistics, University of Wisconsin-Madison, Madison, Wisconsin.
8Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.
9Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin; Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin
Abstract
Purpose: To evaluate the response of the ureter and renal pelvis to direct targeting by histotripsy guided by cone-beam computed tomography (CT) in a human-scale porcine chronic-survival model.
Materials and methods: Bilateral ureteral histotripsy treatments were completed on 6 female swine (n = 12). Animals were divided into 2 groups: (a) acute (n = 2 animals, 4 treatments, sacrificed at Day 0) and (b) chronic (n = 4 animals, 8 treatments, sacrificed at Day 7 [n = 2] and Day 28 [n = 2]). For each treatment, a 2.5-cm sphere (ureter/renal pelvis and renal parenchyma) was targeted using cone-beam CT guidance. CT urography imaging was performed immediately after treatment for all animals, and on Days 7 and 28 for chronic animals, followed by sacrifice, necropsy, and histopathology. Serum chemistries were drawn before treatment and at Days 7 and 28.
Results: All 12 treatments were successful in targeting the renal pelvis/ureter and renal parenchyma. CT urography findings at Day 0 included ureteral thickening (9/12), delayed parenchymal enhancement (3/12), and mild hydronephrosis (5/12), all resolving by Day 7. Histologic findings of low-grade damage resolved by Day 7. No urine leaks or ureteral strictures were observed. Renal function (creatinine and estimated glomerular filtration rate) remained within the normal range throughout the study.
Conclusions: Histotripsy treatment of the ureter and renal pelvis results in transient injuries, suggesting that treatment of central renal tumors adjacent to the ureter and renal pelvis is safe. The results of this study could help expand the range of renal tumors that can be treated with histotripsy.
Vasc Interv Radiol. 2025 Mar;36(3):512-520.e1. doi: 10.1016/j.jvir.2024.11.028. Epub 2024 Dec 9.
PMID: 39662616
Comments 1
The article discusses a study evaluating the effects of histotripsy, a non-invasive ultrasound-based technique, on the proximal ureter and renal pelvis in a porcine survival model. The study aimed to assess any potential tissue damage caused by this treatment, particularly focusing on urothelial injury.
Study Design:
Six female swine were subjected to bilateral ureteral histotripsy treatments, resulting in a total of 12 procedures. The animals were divided into two groups: acute (sacrificed on Day 0) and chronic (sacrificed on Days 7 and 28).
Treatments were guided by cone-beam computed tomography (CT), targeting a 2.5-cm area that included the ureter, renal pelvis, and renal parenchyma. Post-treatment imaging and histopathological evaluations were performed to assess the effects.
Results
Immediate CT urography showed signs of injury, such as ureteral thickening, delayed renal parenchymal enhancement, and mild hydronephrosis, but these conditions resolved by Day 7.
Histological analysis revealed low-grade damage that also cleared by Day 7.
No complications like urine leaks or ureteral strictures were recorded during the study. Additionally, renal function remained stable throughout the observation period.
Summary of findings:
Successful execution of 12 histotripsy treatments using advanced CT guidance. Zransient injuries resolved quickly post-treatment, indicating the technique's safety profile over a 28-day period. The study concluded that histotripsy is a safe method for treating disorders in the renal pelvis and ureter, resulting in only temporary injuries. These findings may allow for expanding histotripsy's clinical application in managing central renal tumors adjacent to these structures without safety concerns for significant complications.
Discussion
Histotripsy is a relatively novel medical technology that utilizes focused ultrasound waves to mechanically disrupt tissue. Here are some key aspects of histotripsy:
Mechanism of Action
Histotripsy employs high-intensity focused ultrasound (HIFU) to generate cavitation bubbles in targeted tissue. These bubbles expand and collapse rapidly, creating mechanical forces that can break down tissue without causing significant thermal injury.The process can selectively disrupt soft tissues, making it particularly relevant for applications in organ systems where precise targeting is crucial, such as the kidneys, liver, and prostate.
Applications
Histotripsy is primarily being investigated for the non-invasive treatment of solid tumors, potentially providing an alternative to traditional surgical approaches, such as resection or ablation. As indicated in this study, histotripsy can be used in the treatment of tumors adjacent to the ureter or renal pelvis while minimizing damage to the surrounding structures.
Advantages
As a non-invasive technique, histotripsy can significantly reduce recovery times and minimize complications associated with traditional surgery. Histotripsy can often be guided in real-time by imaging techniques such as ultrasound or CT, allowing for precise targeting and monitoring during the procedure.Early studies suggest that histotripsy may produce minimal collateral tissue damage, making it a safer option compared to some other forms of ablation that can generate heat (e.g., radiofrequency ablation).
Current Research
Various experimental studies, including the actual paper, are being conducted to evaluate the safety and efficacy of histotripsy in different settings and for various conditions. Research is pivotal in understanding tissue responses, potential complications, and long-term outcomes.
Several clinical trials are ongoing to assess the impact of histotripsy in treating different tumors and conditions, aiming to establish protocols and best practices.
In summary, histotripsy represents a promising advancement in non-invasive treatment methodologies, particularly in the fields of oncology and urology. Continued research will help expand its applications and solidify its safety and efficacy profile.
Jens Rassweiler