Transurethral injection therapy has become a cornerstone in the treatment of various urological conditions, particularly stress urinary incontinence (SUI) and bladder outlet obstruction. One of the most commonly used injectable materials is Bulkamid, a biocompatible synthetic hydrogel composed of polyacrylamide, which is cross-linked to form a stable gel that provides long-term volume enhancement (Sakakibara et al., 2014). Bulkamid offers several advantages over other injectable materials, including reduced risk of migration, minimal inflammation, and the ability to maintain its shape and volume over time (Pannek & Scherbaum, 2017).

Despite its widespread use, the precise distribution and location of Bulkamid after injection remain areas of ongoing investigation. The effectiveness of Bulkamid is closely linked to its precise placement in the peri-urethral tissues, yet the dynamic process of gel migration and absorption within the urethra is poorly understood (Kuo et al., 2016). Currently, imaging techniques such as fluoroscopy and cystoscopy are employed to monitor gel placement, but they lack high spatial resolution and do not offer comprehensive three-dimensional visualization of the material's distribution (Zhu et al., 2018).

In recent years, 3D ultrasound imaging has emerged as a promising tool for assessing injectable biomaterials due to its ability to provide real-time, non-invasive, and high-resolution visualization of tissue and gel distribution (Liao et al., 2015). This study seeks to harness 3D ultrasound technology to provide a more detailed understanding of how Bulkamid behaves in vivo following an uncomplicated transurethral injection.

The ability to accurately map the location and distribution of Bulkamid after transurethral injection is of paramount importance in optimizing clinical outcomes for patients undergoing treatment for stress urinary incontinence and bladder outlet obstruction. The use of 3D ultrasound to track Bulkamid’s distribution offers several potential advantages:

1. Improved Injection Accuracy: The precise localization of Bulkamid via 3D ultrasound could assist clinicians in refining their injection techniques, ensuring more accurate placement of the material. This, in turn, could enhance the therapeutic effect and reduce the likelihood of requiring additional injections (Hancock et al., 2013).
2. Better Understanding of Efficacy: Understanding the spread and distribution of Bulkamid in the peri-urethral region is crucial for correlating the material's placement with clinical improvements in urinary function. Studies have shown that the success of injectable treatments like Bulkamid depends on accurate placement within the target tissue (Zhu et al., 2018). Visualizing the distribution can therefore help elucidate the relationship between material location and patient outcomes.
3. Enhanced Safety Profile: Real-time 3D imaging could also aid in identifying potential safety concerns, such as material migration or excessive bulking in undesirable areas, which may lead to complications or suboptimal treatment results (Pannek & Scherbaum, 2017). Early detection of such issues could improve patient safety and reduce risks associated with improper placement.
4. Personalized Treatment Approaches: The use of 3D ultrasound imaging allows for a more individualized assessment of injection techniques, tailoring the procedure to the patient’s unique anatomical features. This personalized approach could enhance treatment outcomes and minimize the risk of complications (Liao et al., 2015).

Ultimately, this study will provide valuable insights into the dynamics of Bulkamid distribution, potentially leading to improvements in injection techniques and the development of best practice guidelines for its clinical use. By enhancing our understanding of how Bulkamid behaves in the human body, this research could contribute to more effective and safer treatments for patients with urinary disorders.

After receiving institutional review board approval and informed consents, clinical charts will be reviewed of the patients to obtain demographic information and clinical data. Between September 2025 and September 2026, patients undergoing urethral bulking with Bulkamid in clinic or in the operating room will also undergo a 3D EVUS imaging immediately post procedure. All procedures will be performed by fellowship-trained urogynecologists who, as part of a prior multicenter study. Faculty had received training to inject the bulking material in a standardize manner. Three-dimensional EVUS will be performed with BK Medical Ultrafocus (Peabody, MA) for the patients within 1 hour of bulking procedure. The data will be analyzed later by one of the authors. The author/researcher will be trained in ultrasound and will be blinded to the provider performing the procedure. The 3D volumes images were obtained with a 6- to 12-MHz 2052 transvaginal probe with 360° imaging capability. A length of 6 cm will be scanned in 60 seconds with scans every 0.25 mm, thus obtaining 240 scans cumulatively, from which a 3-dimensionally.

The Bulkamid injection procedure will all be carried out in a uniform fashion based on the Bulkamid label instructions. Injections were performed using an operating cystoscope (straight eyepiece with a 0-degree angle of view) and a needle placed in a rotatable sheath. The needle will be inserted through the operating channel and visualized within the bladder. The cystoscope will be withdrawn to the mid- urethra and 0.5 ml of Bulkamid

material will be injected at the 2, 5, 7, & 10 o’clock positions. The order of injections can be based on the provider’s preference. After the procedure, a 3D US will be performed as noted above. A passive voiding trial was performed after the procedure.

During 3D US post-processing, data analysis, the urethra and its cavity will identified in axial view, and the pubic symphysis will used as a marker for 12-o'clock position, and the

location of the center of hyperechoic density was described in 1-and 12-o'clock positions in relation to the urethral cavity. The distance of the injected bulking agent from the UVJ will be measured as follows: The entire length of urethra will be measured in the sagittal view, and the line was drawn from the center of the hyperechoic bulking agent to the urethra in the shortest distance. The distance from the UVJ to this point will be measured.

During the 3D volume analysis, the sagittal view was angled appropriately to include the entire length of the urethra. The length of the urethra was defined as the distance from the bladder opening to the external urethral meatus opening. The bulking agent was noted to be in proximal location if this distance was less than one third of the urethral length.

In addition, the distribution pattern will be described.

To analyze the correlation of ultrasound findings with clinical outcomes, the patients' charts were reviewed to see if the patients' symptoms had improved more than 50% at between 1- and 3-month follow-up.

Data collection ongoing