This PDF file contains the front matter associated with SPIE Proceedings Volume 10852, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

Recently, laser-induced interstitial thermotherapy (LITT) has been investigated and considered a minimally invasive treatment method to achieve deep coagulation in prostate tumor. However, excessive heating in the target region adversely affects the adjacent healthy tissue, possibly leading to thermal injury to critical organs such as urethra, sphincter, erectile nerves, and bowel. The aim of the current study was to develop a pulse-processing model to predict and manage the temperature development and thermal coagulation region during LITT-prostate cancer treatment. A CW 532-nm laser beam was expanded and then focused on the fiber connector by using a combination of concave and convex lens. A shutter was placed in-between the two lens, and all cycle parameters including exposure, delay, and duty cycle were driven by using a control system in conjunction with LabView software. The 5-W 532 nm laser system connected with the pulse–processing model was employed with a diffusing applicator to thermally coagulate liver tissue. The cyclic parameters were divided into three sequential periods: CW mode, pulse-processing mode, and laser-off mode. The results showed that after 15-s irradiation, the local tissue temperature achieved 70 °C. Based on optical and thermal properties of the tissue, the pulse-processing mode with a duty cycle of 70% (exposure time = 350-ms vs. delay time = 150-ms) was calculated and used in the experiment. Due to the pulse-processing mode, the surface temperature was initially maintained at 70 °C for 60 s with a steady-state error of less than 2 °C. The proposed pulse-processing model can be a feasible tool to provide the optimal therapeutic conditions for the LITT-prostate cancer treatment.

Laser lithotripsy depends in part on fragmenting stones to sufficiently small size for spontaneous passage or extracting all large residual stone fragments to provide high stone free success rates, so a second repeat procedure is unnecessary. This preliminary study describes initial development of an optical system and software capable of tracking and labeling kidney stones. Machine learning and image processing techniques were implemented to track, label, and size, on a relative scale, stone fragments. Thresholds were placed on minimum stone fragment size (based on pixel sizes). For system validation, a series of still images from the laboratory setup and previously recorded clinical lithotripsy procedures were analyzed. A laboratory test was also conducted with homogenous background and video to determine number of true positives, false positives, and false negatives. In still images, 8/8 (100%) stones in the laboratory setup and 4/4 (100%) stones in clinical lithotripsy videos were correctly identified. A separate laboratory study correctly identified all five stones in each frame across a total of 110 video frames (550/550) (100%) with a total of 49/550 false positives (9%) and 0/550 (0%) false negatives, at a maximum frame rate of 50 Hz. This preliminary stone tracking study correctly identified stone fragments in laboratory frames for still and motion video and during still images from clinical lithotripsy procedures and experimental settings. Further development of software and optical tracking system is planned.

Urothelial carcinoma (UC) is the most common type of bladder cancer. Its treatment depends from both tumour extension (stage) and aggressiveness (grade). The gold standard for detecting UC is white-light cystoscopy, followed by tissue biopsy and pathological examination for determining tumour stage and grade. However, such process is invasive, time-consuming and prone to sampling errors. In this framework, optical spectroscopy techniques provide fast, label-free and non-invasive alternatives to standard histopathology. Thus, we combined auto-fluorescence, diffuse reflectance and Raman spectroscopies in a compact and transportable setup based on an optical fibre-probe. The latter was coupled to three laser diodes (emitting at 378 nm, 445 nm and 785 nm) and to a halogen lamp for exciting and collecting autofluorescence, Raman and reflectance spectra, respectively. This experimental setup was used for studying fresh biopsies of urothelial tumour (82 samples) and healthy bladder (32 samples) collected from 49 patients undergoing Transurethral Resection of Bladder Tumours (TURBT). All spectral recordings were done within 30 minutes from surgical resection, and optical inspection required less than 2 minutes for each sample. The recorded data were analysed using Principal Component Analysis (PCA) for obtaining an automated classification of the examined samples based on the intrinsic spectral information provided by all three techniques. We found that multimodal spectroscopy provides high-sensitivity, high-specificity discriminating capability for UC detection, grading and staging. The presented strategy generates results similar to gold standard histology, but in a fast and label-free way, offering the potential for endoscopic in vivo applications.

Bladder cancer is the fourth most common cancer in men and is considered to have the highest rate of recurrence of all cancers at ~70%, and transitional cell carcinoma (TCC) is the most common form of intrabladder malignancy. Current standard-of-care for Stages 2 or higher is radical cystectomy, which involves removal of the urinary bladder and nearby lymph nodes. Alternative, organ-sparing treatments such as chemo- or radiotherapy are relatively ineffective against these cancers. The latter is effective when precisely targeted, but suffers from accuracy issues due to low contrast from computed tomography guidance. These motivate an innovative approach to more precisely visualize and spatially pinpoint TCC. This manuscript presents a novel non-invasive computer vision pipeline that can extract 3D structural information from 2D images obtained during routine flexible cystoscopy. The pipeline utilized camera calibration, adaptive thresholding, Scale Invariant Feature Transform (SIFT), and a Structure from Motion (SFM) implementation to reconstruct 3D point clouds of the inner surface of organ phantoms and an ex vivo porcine bladder. 3D point clouds were processed by Poisson reconstruction to generate a textured, triangle meshed 3D surface. The reconstruction pipeline generated a visually recognizable, qualitative 3D representation of the bladder from 2D video captured via flexible cystoscopy. Once further developed, this approach will enhance the targeting precision of external beam radiotherapy, providing clinicians with better organ-sparing methods to treat TCC.

Urethral stricture, also called urethral stenosis, is an abnormal narrowing of the urethra due to scarring on the urinary wall caused by inflammation or trauma. Although various surgical treatments have been developed such as urethrotomy and urethroplasty, the recurrence rate is almost 40 percent due to development of fibrosis in the urethra. The purpose of the current study was to evaluate the effect of phloroglucinol-assisted low-level laser therapy (LLLT) on inhibition of fibrosis in in vitro. LLLT is one of the promising methods for fibrosis treatment, and phloroglucinol has an anti-fibrotic effect. NIH/3T3 fibroblast cells were cultured in a medium containing transforming growth factor (TGF)-β1 to induce differentiation of the fibroblasts. Laser (635 nm at 375 mJ/cm²) and phloroglucinol (100 μg/ml) were treated separately or simultaneously after TGF-β1 was treated. MTT and BrdU assay presented the inhibitory effect of the combined treatment on cell proliferation. An inhibitory effect on migration speed was confirmed by wound healing assay. Confocal immunofluorescence images showed that the combined treatment inhibited the expression of α-smooth muscle action (sma) and type-1 collagen. Moreover, Western blot analysis demonstrated that α-sma, collagen-1, and TGF-β1 as the key factors of fibrosis were suppressed by the combined treatment. Therefore, phloroglucinol-assisted LLLT may be an effective treatment to prevent the recurrence of urethral stricture. In vivo tests will be conducted in canine models for pre-clinical evaluations.

Minimally-invasive alternatives for prostate cancer treatment are an unmet clinical need. We are currently conducting clinical trials using interstitial photothermal therapy (PTT) in focal (intermediate-risk) prostate cancer, targeting the largest (index) lesion, utilizing near-infrared (NIR) laser light that is delivered via one or more laser fibers placed interstitially to cover the target volume. This procedure is done using an interventional MRI suite where real-time MR thermometry is used to monitor treatment progression as a surrogate for tissue coagulation. We investigate here if photoacoustic imaging (PAI) could be used instead of MR thermometry to provide direct and higher specificity/sensitivity monitoring of the coagulation-front, particularly for the purpose of avoiding rectal wall damage. For this, we developed an in vivo canine PTT model and experiments were performed in 6 beagles with intact normal prostates, using similar approaches to those used in ongoing clinical trials. PTT also performed in vivo as well as in ex vivo porcine muscle. Initial results demonstrated the feasibility of both the PTT technique as well as an optimized monitoring platform. In ex vivo porcine muscle PAI demonstrated correlation with temperature (R² = 0.66) that provided the impetus to move in vivo. However, due to noise and the relatively small changes in the PAI signal with coagulation this did not provide as much imaging depth or resolution as MR thermometry, the current gold standard. With newer PAI probes and deployment of the PAI light sources, it may be possible to increase the sensitivity of PAI for in vivo treatment monitoring. This work was supported by the Terry Fox Research Institute (Grant #1075).

This preliminary study investigates an automated, vibrating fiber tip for dusting of kidney stones during Thulium fiber laser (TFL) lithotripsy. A (0.75-mm-diameter, 5-mm-length) magnetic bead was attached to the fiber jacket 2 cm from distal fiber tip, and a solenoid made of ferrite material was used to create a magnetic force on the bead, inducing fiber vibration. Calibration tests for fiber motion in both air and water were performed. Uric acid (UA) stones were ablated using 50-, 100-, and 150-μm-core fibers, and ablation crater characteristics (surface area, volume, depth, and major/minor axis) were measured using optical coherence tomography after delivery of 1500 TFL pulses at 1908 nm, 33 mJ, 500 μs, and 300 Hz. The resonant frequency was dependent on fiber diameter and rigidity, with a cutoff pivot point for optimum motion of 3 to 4 cm. Maximum fiber displacement was about 1 mm in water and 3.5 mm in air. For all fiber diameters tested, ablated surface area was two times greater with vibrating fiber. Similar ablation volume was removed with vibrating and fixed fibers, consistent with previous literature reporting similar ablation rates independent of fiber diameter, given a fixed energy per pulse. This preliminary study demonstrated functionality of an automated, vibrating fiber system for stone “dusting”, with two times larger surface area but equivalent ablation volumes as a fixed fiber. Continued development of this method is warranted, with emphasis on optimization of fiber parameters (especially displacement) and miniaturization of components for future integration into ureteroscopes.

Laser lithotripsy is now the preferred treatment option for urolithiasis over Shock wave lithotripsy (SWL) for renal stones smaller than 1.5 cm due to shorter operation times and a better stone-free rates (from the retrospective study by E. B. Cone et al). Nonetheless, the detailed mechanism of calculus disintegration by laser pulse remains relatively unclear. One of the fundamental parameters for laser stone interaction is the ablation threshold. Richard L. Blackmon, et. al. have studied the ablation threshold for Ho: YAG and the thulium fiber lasers (TFL) in terms of the laser energy density. However, an ablation threshold in terms of peak power density would be more universally applicable. In this study, two commercially available Ho: YAG lasers were used as the laser pulse source. The fibers used in the investigation are SureFlexTM fibers, (Models S-LLF273 and S-LLF365) with 273 and 365 μm core diameters, respectively. Calculus phantoms were made of the Bego stone material with various degrees of hardness. These stone phantoms were ablated with the Ho: YAG lasers at different peak power densities. The laser pulse width was measured utilizing a 2 μm photodiode (Thorlabs DET10D), and the laser-induced crater volumes were evaluated with a 3-D digital microscope (Keyence VHX-900F). In this way, we determined the ablation threshold as a function of peak power density for the Bego stone phantoms with 3 different hardness values. Additional investigations of the ablation threshold of other stone types will be conducted in a future study.

Dual pulse mode has recently been integrated into Holmium:YAG laser systems to reduce stone retropulsion. This study explores similar pulse shaping approaches with Thulium fiber laser (TFL). A TFL at 1940 nm wavelength produced three temporal pulse profiles: (1) square pulse, (2) dual pulse, with low energy initial pulse followed by higher energy second pulse, and (3) ascending staircase pulse shape. Energies of 0.1 - 2.0 J, pulse rates of 5 - 200 Hz, average power of 10 and 20 W, and laser irradiation time of 5 s were used (n=5 per group). Stone phantoms (6-mmdiameter, 200-mg-mass) were placed on a horizontal, v-shaped trough, submerged in water, and then irradiated with TFL using a 200-μm-core optical fiber. Dual pulse stone displacements using pulse energies of 0.1, 0.2, 0.5, 1.0, and 2.0 J, measured 65%, 75%, 100%, 100%, and 110% of square pulse displacement at 10 W, and 65%, 60%, 60%, 90%, and 105% of square pulse displacement at 20 W. Staircase pulse stone displacements measured ~ 85% of square pulse stone displacement at 1.0 and 2.0 J for both 10 and 20 W. At lower energies (0.1 - 0.5 J), staircase profile produced a suction effect, resulting in the stone being pulled back to the fiber. Dual pulse mode only reduced stone retropulsion at lower energy settings, possibly due to excessive energy in initial pulse at higher settings. Low power (10 W) square, dual, and staircase pulse shapes ablated uric acid stones at rates of 1.7 ± 0.4, 1.9 ± 0.5, and 1.7 ± 0.5 mg/s, respectively. High power (20 W) square, dual, and staircase pulse shapes ablated stones at a rate of 2.6 ± 0.6, 3.0 ± 0.4, and 2.7 ± 0.7 mg/s, respectively. Future studies will utilize optical imaging of vapor bubble formation as a function of temporal pulse profile to optimize laser parameters for reducing stone retropulsion and enhancing TFL stone ablation rates.

Introduction: The Moses technology for the Ho:YAG laser introduces a pulse-shape modulation that optimizes energy delivery through water. The aim of this study was to assess fiber tip to stone working distance on fragmentation incorporating a variety of pulse modes. Methods: Experiments were conducted with a 3D positioner, a 30 mm flat BegoStone, and a 230 µm fiber utilizing short pulse (SP), long pulse (LP), Moses Contact (MC), and Moses Distance (MD) modes. Ablation crater volume was measured by 3D confocal microscopy, after a single pulse (1.0J) with the fiber tip positioned at 0, 0.5, 1, 2, and 3 mm from the stone. Fragmentation efficiency (1Jx10Hz) was assessed with the fiber tip at 0 and 1 mm distance, programmed to fragment the stone over 3 minutes. Fragmentation was defined as difference in stone mass before and after each experiment. Results: For all tested pulse modes, ablation crater volume and fragmentation were greatest when the fiber tip was in contact with the stone. Ablation declined as the working distance increased with no ablation occurring at 3 mm. At 1 mm distance, ablation volume using MD mode was significantly higher when compared to SP, LP and MC (p<0.05). Compared to all modes tested, MD resulted in 28% and 39% greater fragmentation at both 0 and 1 mm working distance, respectively (p<0.05). Conclusion: Holmium laser lithotripsy is significantly affected by fiber working distance. At 0 and 1 mm distance, MD had the greatest fragmentation efficiency suggesting this mode may have advantages during ureteroscopy.

The experimental Thulium fiber laser (TFL) is currently being explored as an alternative to the gold standard Holmium:YAG laser for lithotripsy. The TFL emits laser radiation at two primary wavelengths, 1908 or 1940 nm, which closely match high and low temperature water absorption peaks in tissue, respectively. Water is a primary absorber of infrared laser radiation, and is present in the pores of kidney stones in the urinary tract. Constant saline irrigation is also applied through the ureteroscope working channel to clear stone debris and improve visibility and safety during lithotripsy. Previous studies have shown that the water absorption peak shifts from 1940 nm to 1920 nm, as water temperature increases heating. At high water temperatures, the absorption coefficient (μa) is ~ 150 cm^-1 at 1908 nm and ~ 135 cm^-1 at 1940 nm. The goal of this study was to determine whether this 10% difference translates into a measurable difference in kidney stone ablation rates. Two Thulium fiber lasers (1908 and 1940 nm) were tested at similar laser parameters of 35 mJ energy per pulse, 500 μs pulse duration, 300 Hz pulse rate, and 10.5 W average power, with energy delivered through 200-μm-core optical fibers. The handheld fiber was maintained in contact with 6-9 mm diameter uric acid (UA) stones, immersed in a saline bath with saline flow (n=10 stones per group). Time to fragment and pass all stone fragments through a 1 mm sieve was measured, and then divided into initial stone mass to calculate ablation rate. For each laser group, 1908 and 1940 nm, initial stone mass was 270 ± 60 mg vs. 260 ± 50 mg, respectively (p = 0.9). Stone ablation rates measured 0.9 ± 0.2 and 0.9 ± 0.1 mg/s, respectively (p = 0.9). Stone ablation thresholds also measured 8 ± 7 and 5 ± 13 J/cm2, respectively (p = 0.8). There was no significant difference in UA stone ablation thresholds and ablation rates between 1908 and 1940 nm TFL wavelengths.

Recent advances in Holmium and Thulium fiber lasers (TFL) enable operation at similar parameters for comparison. A ‘dusting’ lithotripsy mode with low energy per pulse (0.2-0.4 J) and high pulse rates (50-80 Hz), is preferred to produce smaller residual stone fragments for natural passage through the urinary tract. Holmium and TFL were compared for dusting using three groups, G1: 0.2 J/50 Hz/10 W; G2: 0.2 J/80 Hz/16 W; and G3: 0.4 J/80 Hz/32 W. A setup with 1 x 1 cm cuvette and 1.0 mm sieve was used with total laser operation time limited to ≤ 5 min. Calcium oxalate monohydrate (COM) stones with average initial stone mass of 216-297 mg between groups were used. Holmium ablation rates were lower than for TFL at all settings (G1: 0.3 ± 0.2 vs. 0.8 ± 0.2; G2: 0.6 ± 0.1 vs. 1.0 ± 0.4; G3: 0.7 ± 0.2 vs. 1.3 ± 0.9 mg/s). TFL also produced a greater percentage by mass of stone dust (< 0.5 mm) than Holmium. For all three settings, 1/15 (7%) stones treated with Holmium were fragmented in ≤ 5 min vs. 9/15 (60%) stones treated with TFL. These preliminary studies demonstrate that TFL is a viable laser for stone dusting, producing higher stone ablation rates and smaller stone fragments than Holmium laser.

Flexible cystoscopy is a widely used diagnostic and therapeutic procedure in urology. However, some dangerous bacteria are resistant to traditional antibiotics. Thus, the current study introduced a combination of glutaraldehyde (GTA), 808- nm, and 405-nm laser to disinfect Staphylococcus aureus bacterial biofilms inside flexible cystoscopes based upon a Teflon tubing model. Based upon the pilot study, the samples were exposed either under GTA (0.5% in 180 s), 808-nm (1.6 W/cm² in 180 s), and 405-nm laser (1.6 W/cm² in 180 s) alone or their combinations. An infrared (IR) camera was deployed to provide the real-time monitoring of temperature development on the biofilm surface while colony forming unit (CFU) analysis was employed to count viable cells before and after the treatment. The preliminary results showed that GTA, 808-nm, and 405-nm laser alone could induce a 2.2-, 1.4-, and 2-log₁₀ CFU/cm² reduction of S. aureus bacterial biofilm, respectively. However, their triple combination could eradicate around 6.5-log₁₀ CFU/cm² reduction in microorganism population. Therefore, the triple combination may be a useful modality for cystoscope reprocessing to prevent any secondary infection in the urinary tract during the cystoscopy.

Previous Thulium fiber laser (TFL) studies using fiber optic muzzle brake tips reported reduced stone retropulsion and distal fiber tip degradation. This study compares muzzle brake tips of various dimensions using the TFL at 1908 and 1940 nm wavelengths in terms of stone phantom retropulsion displacement using a pendulum setup, needle hydrophone pressure transient measurements, and uric acid (UA) stone ablation rates. Low and high TFL pulse energies of 35 and 140 mJ, 500 μs pulse duration, and pulse rates up to 300 Hz were used with 100- and 200-μm-core optical fibers. “Small”, “medium”, and “large” muzzle brake tips dimensions measured 180/340, 360/560, and 550/710 μm inner/outer diameter, respectively, with a porthole positioned 500 μm from distal muzzle brake end. Pendulum displacement measured 50%, 200%, and 50% of bare trunk fibers for small, medium and large muzzle tips, respectively, in optimal configuration. Needle hydrophone pressures measured 300%, 20%, and 50% of bare trunk fiber for small, medium and large muzzle tips, respectively, in optimal configuration. Stone ablation rates at low pulse energy (35 mJ) were maintained for medium muzzle brake tips while small and large muzzle brake tips performed about 10 and 7.5 times worse than bare fibers. At high pulse energy (140 mJ), the large muzzle tip performed similar to a bare 200-μm-core fiber with 100%, 50%, and 100% the displacement, pressure, and ablation rate. These studies show feasibility of modifying muzzle brake tip dimensions to obtain comparative ablation rates and minimal stone retropulsion for lithotripsy.