This PDF file contains the front matter associated with SPIE Proceedings Volume 12353, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

Stone retropulsion is an inevitable side effect of laser lithotripsy. It is generally considered undesirable but can also be beneficial in techniques such as “popdusting”. It is often described by a single parameter such as a distance moved, which might not correlate with the degree to which retropulsion interferes with clinical use. We report on a novel method of measuring retropulsion in vitro using high-speed video photography to describe the stone trajectory across multiple parameters, and present results from a range of laser systems. Describing the nature of this movement may help explain how some types of retropulsion are considered clinically disruptive and others are not.

Surfactants reduce vapor bubble surface tension and increase bubble dimensions, which may potentially enable longer non-contact working distances during laser lithotripsy and/or lower laser energy for creating bubbles. This study compares vapor bubble characteristics of two commercially available surfactants over a wide range of concentrations and laser parameters. A Thulium fiber laser (TFL) at 1940 nm delivered single laser pulses through 200-μm-core fibers with 0.22 numerical aperture, in a 9.5 L water tank. The TFL was operated with four laser settings, at constant peak power of 200 W (50 mJ / 250 μs; 100 mJ / 500 μs; 200 mJ / 1000 μs; 500 mJ / 2500 μs). Two surfactants (Tween 20 and 80) were tested with concentrations of 0% - water (control), 0.1%, 1%, and 10%. A total of ninety-two experiments were conducted: (2 surfactants x 3 concentrations x 4 parameters x 3 tests) + 20 tests in water). A highspeed camera operating at 200,000 frames per second and with 256 x 160 resolution, imaged bubble dimensions. ImageJ and MATLAB software were used to analyze bubble dimensions. A 1% concentration of Tween 20 provided optimal results, balancing increased bubble dimensions with solubility and visibility. At 1%, Tween 20 produced 5.3% and 8.0% greater bubble lengths than Tween 80 and water, respectively, and 5.4% greater bubble width than water. Bubble lifetime increased with increasing surfactant concentration, and the number of bubbles in a laser pulse also increased with laser pulse energy and pulse duration for all parameters tested. Tween 20 yields longer bubble lengths than water and Tween 80, for potential use as an irrigant during laser lithotripsy.

Stress urinary incontinence (SUI) is the unintentional loss of urine. Currently, catheter and artificial urinary sphincters are applied for SUI treatment. However, these treatments are invasive and require continuous usage. While Er:YAG and CO2 lasers are used as a minimal or non-invasive method, their treatment effects are limited to the superficial vaginal tissue and can often cause severe burns, leading to tissue destruction. The purpose of this study to investigate the feasibility of non-ablative 980-nm laser treatment for SUI. Numerical simulations were performed to confirm thermal effects in urethral tissue by employing the Pennes bioheat transfer and partial differential equations. Rabbit urethral tissue was used for experimental validations. A non-compliant balloon was used to expand the urethral tissue, and the 980 nm laser light was irradiated on the tissue at 20 W for 15 s. After the laser irradiation, the treated samples were stained with hematoxylin and eosin (HE) to evaluate any physical changes in the overall urinary structure. Masson trichrome (MT) staining was performed to analyze the extent of thermal injury in the collagen of the urethral tissue. A uniform and symmetrical temperature distribution was observed around the balloon surface in the simulation. The numerical simulations and experiments indicated that mucosal and muscle layers in the urethral tissue reached the temperatures of 24 °C and 31 °C, respectively. Histology analysis presented the overall urinary structure with a total outer diameter of 10 mm from the mucosal layer to the muscle layer. The MT staining revealed that both control and treated groups had similar amounts of collagen components without thermal damage. The current study demonstrated that the non-ablative 980 nm laser could warrant an effective method of treating SUI with no or minimal thermal damage.

Among malignant tumors, prostate cancer is the second most found in men. Non-invasive methods using lasers, Photodynamic therapy (PDT) and Photothermal therapy (PTT), have been mainly studied as treatments. However, they have several limitations such as the intrinsic hypoxia of PDT and the unsafety for temperature of PTT. Therefore, in this study, PDT and PTT were combined by using conjugated photothermal agents (PA). For PDT-PTT, 635 nm laser light (1 W/cm² for 5 min) was used. DU145, human prostate cancer cell line was used for in in vitro tests. Cytotoxicity test using MTT and ROS detection test were conducted to evaluate the condition of PDT combined PTT. The cellular death was classified whether apoptosis or necrosis using flow cytometry with Annexin V/PI. PDT over a certain period confirmed to be less effective, and at the same time, the cell death rate increased by about 12 % when PDT and PTT were combined, proving the effect of tumoricidal effects compared to conventional PDT. During combined treatment, the cellular death of tumor was occurred through apoptosis and necrosis simultaneously. The current study demonstrated the PTT combined PDT increased anti-tumor effect with lower proliferation and inflammatory.

Cystoscopy has limited ability to detect ureteral injury caused by electrosurgical device lateral thermal spread during gynecologic procedures. We assessed the feasibility of endoscopic optical coherence tomography (OCT) to detect electrothermal ureteral damage. A convolutional neural network (CNN) was developed to automate detection and to provide higher-level insights into characteristic features of electrothermal injury on OCT images. Bipolar electrothermal energy was externally applied to nine freshly excised porcine ureters. Three segments of each ureter were treated for 5 seconds at low (16 watts), medium (26 watts), and high (36 watts) powers (total n = 27). Volumetric OCT images of each lesion were acquired using a swept source OCT laser endomicroscopy system (Ninepoint NVisionVLE). Lesions were compared to untreated controls on histology. OCT datasets were visually inspected for characterization of normal and electrothermally injured tissue architecture. Based on ground-truth interpretation, labelled images were used to train and validate the machine learning algorithm. The effect of power on lesion length as measured with OCT was compared using a one-way analysis of variance. Transmural electrothermal injury was detected in all histology-matched lesions (23/23, 100%) on OCT images. The mean lesion size on OCT was 0.36 ± 0.2 cm, 0.43 ± 0.1 cm, and 0.70 ± 0.3 cm for low, medium, and high powers, respectively (p=0.017). The CNN successfully identified all lesions but with several false positives, including artifacts from tissue dissections, needles, and air pockets. Endoscopic OCT could fulfill an unmet clinical need for the timely detection of electrothermal ureteral damage.

Cervical cancer is a fatal disease with over 50% of modality rate. Although chemo and external beam (EB) radiation are used for cancer treatment, radiation therapy has a limited effect and toxicity. Interstitial-photodynamic therapy (I-PDT) is a promising method for locally advanced cervical cancer (LACC). However, there are still challenges to reducing the totoxicity of photosensitizer and improving photoactivation. Thus, we propose a sodium copper chlorophyll (SCC), organic compound, as a photosensitizer. The purpose of this study is to investigate the feasibility of SCC as a photosensitizer, and develop an effective LACC treatment through SCC mediated I-PDT. The proposed therapy was evaluated on human cervical carcinoma cells and HeLa xenograft tumor models. After SCC injection (4 μg/ml and 0.1 g/kg), a 405 nm blue light (BL; 800 mW/cm²) was applied using a frontal (EB-PDT) and diffusing (I-PDT) fiber. SCC or BL was hardly cytotoxic (less than 10%) on cancer cells independently, whereas SCC mediated PDT rapidly and strongly reduced the viability. High intensity of ROS was measured within 20 min after treatment. In addition, SCC mediated PDT stimulated the expressions of cleaved caspase 3, 8, and 9 with downregulated pro-caspase. Moreover, the proposed I-PDT decreased tumor size by up to 37% less than EB-PDT with minimal thermal damage around tissue. The current study demonstrated the potential antitumor effect of SCC mediated I-PDT in human cervical carcinoma cell and xenograft tumor model as a result of biocompatible photosensitizer and improved photoactivation. Therefore, SCC mediated I-PDT can warrant an effective treatment of LACC.

As more and more small core fibers (sub 300 μm) become available for high-power laser application (>20 W), fiber distal-tip degradation during ureteroscopic laser lithotripsy (URSL) is critical. Still, it is an overlooked aspect due to its subtle effect on the ablation rate and lack of adequate characterization. The objective of this study is to measure fiber tip degradation in terms of surface modification and output beam profile. The fiber tip is a location of interest not only because fiber material performance at the tip impacts laser beam shape, power, and quality but moreover because this is the primary region where inter-procedural degradation compounds. By characterizing the degradational relationship between laser beam profile and fiber tip damage, the next generation of fiber development could be motivated to improve URSL procedures. A high-magnification microscope was used to investigate the fiber tip surface degradation due to laser dose with or without a stone phantom. A single-mode 660 nm laser beam and an M-square measurement system were used to evaluate the laser beam profile variation through lithotripsy fibers with different distal end degradations. The results show that the laser beam profile through the fiber varies with the core size of the fiber and distal end degradation.

Urethral stenosis is a narrowing of the urethra caused by inflammation, or surgical trauma. Although endoscopic managements have been applied for short stricture, high recurrence rates and complications have still remained. Recently, balloon-assisted cylindrical laser ablation using a diffusing applicator (DA) has been investigated to treat tubular tissue [1,2]. Even though previous studies confirmed the safety and efficacy [1,2], performance validation is still unmet for clinical situations. This study aims to establish treatment conditions by quantifying treatment length and depth for the clinical translation. Ex vivo experiment on porcine liver tissue was conducted to compare various energy levels under static and dynamic conditions. A glass tube was inserted into the liver tissue and filled with water. DAwas then located at the center of the glass tube to deliver laser light in the radial direction, leading to cylindrical ablation of the liver tissue. After irradiation of 532 nm at 20 W, ablation length and depth were assessed. The extent of the coagulated region was increased with the irradiation time in both static/multiple and dynamic conditions. Dynamic condition showed the maximum ablation length after irradiation at 20 W for 20 s. All the ablation depths were found in the range of 2.0 ~ 2.5 mm, except the 20W for 15 s in the static condition. The current study confirmed that balloon-assisted cylindrical laser ablation can regulate the ablation region by adjusting treatment conditions depending on the extent of the stricture. Further in vivo studies will be investigated to assess current findings in terms of acute and chronic responses for clinical translation.

Miniature ureteroscopes (< 2-mm-outer-diameter) may potentially enable less expensive, office-based, laser lithotripsy in the lower urinary tract with patients only requiring local anesthesia. This preliminary study describes a flexible miniature ureteroscope design combining illumination and irrigation channels using a saline liquid light guide (LLG). Teflon AF 2400 is a novel, flexible, biocompatible material with lower refractive index (n = 1.29) than saline (n = 1.33), thus enabling total internal reflection (TIR) of light through an LLG. Irrigation rates were measured through an annulus-shaped LLG, sandwiched between concentric inner (OD = 0.74mm / ID = 0.61mm) and outer (OD = 1.60mm / ID = 1.02mm) Teflon AF 2400 tubing. A flexible plastic fiber optic imaging bundle (7.4k pixels / OD = 0.5mm / NA = 0.5) was placed within the inner Teflon tubing core. Two optical fibers of 0.100-mm / 0.140-mm / 0.170-mm (core/cladding/buffer) were placed between the Teflon layers, as spacers, steering cables, and for energy delivery. Computational fluid mechanics models (ANSYS) and optical simulation software (Zemax) were used to predict irrigation rates and illumination, respectively, over a wide range of Teflon dimensions. Computational models calculated gravitational flow rates up to 12.8 ml/min for a larger annulus with concentric inner and outer Teflon AF tubing dimensions of 0.74-mm-OD and 1.80-mm-ID, with two fiber spacers decreasing annular flow by an additional 10%. Optical simulations predicted optimal illumination out of the annulus-shaped saline light guide of 72-77% of initial input. The LLG flexible ureteroscope design utilized concentric Teflon AF tubing for TIR of light through an annulus-shaped irrigation channel, minimizing cross-sectional area, for a miniature ureteroscope (< 2-mm-OD). With further development, miniature ureteroscopes may enable an office-based approach to laser lithotripsy.

Background: Cystoscopy is a common endoscopic procedure to examine the lower urinary tract, particularly the bladder, for potential tumors, lesions, or other sources of hematuria. Cystoscopy has recognized shortcomings including missed tumors and differentiation of benign from cancerous lesions. Clinical outcomes are affected by variable provider experience. Deep learning models have been proposed to address these issues. Because real-time cystoscopy consists of sequential frames, we explored a novel class of DL models to classify frames of bladder tumors using sequential inputs.

Materials and Methods: We considered four state-of-the-art sequential models (SlowFast, Multiscale Vision Transformers, X3D, and CNN-LSTM). Models were trained with different sequence lengths. The development set consisted of 196 10-second video clips from 76 cystoscopies (70 patients). The validation set consisted of 68 full-length cystoscopy videos with 216,870 frames (60 patients) were annotated for pathologically confirmed bladder tumors. Model performance was measured according to sensitivity, specificity, and AUC at the frame-level for detection of region of interest (ROI). We also collected the inference time for each model to assess real-time feasibility.

Results: Model performance varied by model architecture and sequence length. We defined three new evaluation metrics: per-ROI accuracy, per-block sensitivity, and per-block specificity. The best performing model (X3D) with a sequence length of 8 achieved a per-ROI sensitivity of 100%, per-block sensitivity of 94.7%, and per-block specificity of 80.0%. X3D also provided the best trade-off between accuracy and efficiency.

Conclusion: Sequential modeling has the potential to accurately classify a wide variety of bladder tumors in a real-time setting.

Non-muscle invasive bladder cancer (NMIBC) is a form of cancer with a high recurrence rate and limited treatment options. Currently best results are achieved when BCG (Bacillus Calmette-Guerin) is used together with photodynamic diagnosis (PDD) and TURBT (trans urethral resection of bladder tumor) but majority of NMIBC still recur after the initial treatment. Even though PDD is commonly used to visualize the lesions as part of a TURBT procedure, photosensitive drug compounds have had limited success in clinical setting partly because of limitations in light sources and light delivery optics.

Modulight has extended its multi-indication laser platform to support the use of a novel photosensitive drug for NMIBC. The properties of different tumor types (papillary vs carcinoma in situ (CIS)) require different illumination methods and laser parameters and illumination modes have been defined accordingly. Laser system has been designed to support both focused illumination of localized lesions and overall illumination of the entire bladder to cover possible scattered CIS lesions. Light delivery system optimization has included compatibility testing with flexible cystoscopes and investigation of the light delivery system performance in bladder environment. Connectivity features of the laser system have been tailored to support documentation requirements in clinical trials by enabling treatment configuration and realized treatment log storage in Modulight cloud. Ongoing work and future plans include treatment monitoring and imaging capabilities integration in treatment flow with the aim to have a comprehensive laser platform that can support white light imaging, fluorescence imaging, and a variety of light-based treatment modalities

Adequate lesion detection is critical in cystoscopy to improve bladder cancer resection and decrease recurrence. In particular, flat-appearing cancer such as carcinoma in situ is difficult to discern by standard white-light cystoscopy (WLC). The adoption of blue-light cystoscopy (BLC), an adjunct imaging technique, remains modest due to the expensive equipment required. We developed a deep-learning algorithm, CystoNet-F, for augmented detection of flat lesions on WLC. CystoNet-F was designed to augment WLC in lesion detection by incorporating domain translation of CycleGAN, transfer learning, and region of interest (ROI) detection. We constructed a development dataset of 40 patients for algorithm training and 10 patients for testing. In the training phase, features from both WLC and BLC were learned and embedded in the algorithm as the model weights of an ROI detector. Transfer learning was performed by fine-tuning CystoNet-F on BLC using the weights learned from WLC. We applied CycleGAN for domain translation between WLC and BLC. In the test phase, WLC input was first translated to the BLC domain and then served as the input of the ROI detector to finally generate a mask on the lesion area. CystoNet-F can produce flat lesion predictions close to urologist’s annotations on the validation set without paired BLC information. The proposed deep-learning algorithm may improve the diagnostic yield of standard WLC in a noninvasive and cost-effective fashion.