This PDF file contains the front matter associated with SPIE Proceedings Volume 11619, including the Title Page, Copyright information, and Table of Contents.

Welcome and Introduction to SPIE Photonics West BiOS conference 11619: Advanced Photonics in Urology.

A current challenge is providing an accurate diagnosis in a timely manner for patients at risk of having prostate cancer. We developed and demonstrated a non-destructive procedure in which 12 biopsies can be cleared, fluorescently labeled, imaged with an open-top light-sheet (OTLS) microscope, and then diagnosed by a pathologist within an hour of biopsy. Using conventional histology as the gold standard, the accuracy, sensitivity, and specificity of 1Hr2Dx were all >90%. Such a method could potentially provide patients with a preliminary on-site diagnosis after a biopsy procedure, thereby alleviating anxiety and potentially expediting treatments.

Transperineal laser ablation (TPLA) treatment of prostate cancer allows for a minimal invasive treatment approach. However, understanding of the ablation zone development and the 3D size are crucial for accurate treatment of prostate cancer. Therefore, we developed an ex-vivo experimental focal laser ablation set-up using a 1064nm CW diode laser to simulate a TPLA treatment, using human prostate and porcine liver. We quantitatively evaluated the thermal distribution and ablation zone volume on high-resolution MR imaging and histopathology to determine the 3D size of the ablation zone. These results allow for development of a dosimetry model of clinical TPLA treatments.

Accurate detection and diagnosis of prostate cancer remains challenging even with MRI fusion ultrasound biopsy procedures. These challenges contribute to diagnostic errors that can lead to repeat procedures. This study explores the application of ex vivo structured illumination microscopy (SIM) to generate pathology images of fresh biopsies to inform diagnostic decisions. Samples from the lesion of interest and a benign area of each patient were obtained, stained with fluorescent H&E analog dyes, imaged on a custom SIM system and diagnosed by a pathologist. This procedure could be extrapolated to a “see-and-treat” paradigm for localized prostate cancer ablation in the future.

Transperineal laser ablation (TPLA) treatment of prostate cancer allows for a minimal invasive treatment approach. However, a predictive dosimetry model for accurate treatment planning for prostate cancer is not yet available. Therefore, we simulated TPLA treatments on porcine liver and quantitatively evaluated thermal distribution and histology slides were made. Hereby, we determined the cumulative equivalent thermal isoeffect dose at 43°C (CEM43) that predicts cell death and led to the development of a dosimetry model.

Holmium:YAG laser has been the lithotrite of choice for around 30 years in kidney stone surgery. Lasers have evolved over the years to offer higher power, increased pulse frequencies and longer pulse durations. The drivers for change have been to improve stone ablation and to minimise retropulsion. We report on a new prototype Holmium laser that fires multiple “micro-pulses” in “pulse packets” and discuss the stone phantom ablation rate results utilizing a bench model. The prototype laser demonstrated impressive stone ablation rates in our bench testing across a range of power settings. We will discuss the details of these results supporting that pulse-modulation with packets of micro-pulses are a promising technological development. (Disclaimers: Bench Test results may not necessarily be indicative of clinical performance. The testing was performed by or on behalf of BSC.

Thulium fiber laser (TFL) lithotripsy has recently been introduced in the clinic. Previous TFL laboratory studies demonstrated successful high-power delivery through ultra-small (50-150-µm-core) optical fibers. This preliminary study simulates the forces on fibers during insertion into an ureteroscope and determines the mechanical feasibility of ultra-small fibers in a clinical setting. Simulations were conducted for commercially avalaible silica fiber sizes (core/cladding): 50/70, 72/108, 100/140, 150/165, 150/180, and 200/240 μm. Solidworks software intregrating Euler’s buckling equation was used to calculate fiber buckling thresholds as a function of typical manual forces (0.3- 2.0 N) applied near the proximal end of a standard ureteroscope. Forces on fibers being inserted were modeled, assuming support from saline flow and resistance by the working channel wall. Simulation results were categorized based on force values previously reported in the literature, with smaller forces (< 0.4-0.8 N) buckling fibers, midrange forces (0.8-1.6 N) optimal for fiber manipulation, and higher forces (>1.6-2.0 N) at risk of damaging the working channel. Fiber sizes were simulated with two different types of holdings on each end to find a range of possible values that most closely simulate clinical behavior. The smallest usable standard flat tip fiber was found to be 150/190-μm (core/cladding), assuming a cladding thickness of ten times the laser wavelength of 1.94 μm (or extra 40 μm OD) to prevent leakage of evanescent waves through the core/cladding interface. The smallest usable ball tip fiber was found to be 110/150 μm. Numerical simulations predicted that optical fibers for TFL lithotripsy should be larger than 110/150 μm to provide effective manual manipulation within flexible ureteroscopes.

Holmium:YAG laser is commonly used as an efficient technology for lithotripsy, breaking urinary stones into small particles (dust) and larger residual fragments (RF). One of the ultimate goals is to create fine dust for real-time aspiration, eliminating the need for mechanical retrieval of RFs. A recent study of stone dust definition suggests a maximum particle size of 250-µm to allow complete aspiration through the working channel of a flexible ureteroscope. We have evaluated the particle size generation of a concept Holmium:YAG laser utilizing a pulse width modulation technique. This technology delivers numerous low-energy micro-pulses per pulse with long temporal pulse duration to potentially enable finer dust particles, better ablation rate, and reduced retropulsion. Overall, the concept device generates a high percentage of fine dust compared with prior results found in literature. (Disclaimers: Bench Test results may not necessarily be indicative of clinical performance. The testing was performed by or on behalf of BSC. Data on file. Concept device or technology. Not available for sale. This device is not yet available for sale in the United States).

Stone retropulsion during laser lithotripsy results from various physical phenomena such as recoil momentum, bubble dynamics, and subsequent jet formation. Considerable stone retropulsion has been observed whereby the optical energy is converted into both mechanical and thermal energy as a distinctive bubble generation and collapse. It is hypothesized that by reducing the peak power and lengthening the pulse duration, we can reduce this conversion of optical energy into mechanical energy. This should maximize the thermal effects on the stone leading to enhanced ablation efficiency as well as less stone “chasing”. We are reporting on a new prototype Holmium laser with low pulse power and long temporal pulse durations in an attempt to minimize stone retropulsion.

Background: Visual stimuli are recognized to stimulate urinary urgency and urgency urinary incontinence (UUI). Current pathophysiology recognizes the importance of cortical control over micturition, but as clinicians lack any methodology to evaluate causal triggers, a MRI protocol for urologic use that explores the brain’s response to visual triggers in subjects with clinical symptoms of trigger-related UUI was developed. Methods: Using a 3 Tesla Philips Elition Scanner, structural T1 weighted images were acquired and used to define ~200 brain regions based on a validated brain atlas. Diffusion Tensor Imaging (DTI) and Myelin Water Fraction (MWF) scans were then obtained to investigate for myelin abnormalities. A functional MRI (fMRI) component followed, where, during scanning, patients were shown a defined random sequence of visual stimuli that consisted of subject-specific trigger images supplied by each subject, interspersed with neutral images. The fMRI study was performed after natural bladder filling. Results: N=10 subjects participated (6 asymptomatic controls and 4 with UUI). Debriefing confirmed that images within the sequence had triggered symptoms of UUI; tractography demonstrated robust structural connectivity between the anterior cingulate cortex and periaqueductal grey matter. Discussion: Conventional investigation of UUI lacks evaluative methodology for the impact of visual triggers on sensation of urgency and onset of incontinence, yet cortical control is recognized to be a major component of UUI in large numbers of the affected population. Conclusion: We describe the feasibility of a novel 1 hour 6 minute fMRI protocol for evaluation and quantification of the cortical mechanisms underlying visual triggers for UUI.

Novel technological solutions for diagnostics and treatment support for inflammatory and noninflammatory (urethral pain syndrome (UPS)) processes in urethra are an urgent task in urology. Visualization of normal and pathologically changed female urethral wall was performed using two types of cross-polarization optical coherence tomography (CP OCT) probes: forward-looking flexible probe and side-looking needle-type one. The advantage of the needle-type probe was the ability to visualize the urethra along its entire length in a short time. Forward-looking probe was convenient for the combined examination of the urethra and urinary bladder in one procedure. In consequence of using CP OCT method, consistent patterns of changes in epithelial and connective tissues of the urethra as a result of inflammatory processes and during UPS were revealed, which cannot be obtained by other methods available in the current clinical practice.

A novel diode pumped Tm:YAG laser (Pantec Biosolutions AG) with a more flexible temporal pulse regime is available. This study includes first experiments with model stones on the influence of the pulse regime on the fragmentation rate. For this purpose, ablation experiments were performed on rectangular model stones (BEGO, 40 mm x 10 mm x 5 mm). The laser beam was coupled into a 270 μm light guide and the distal fiber end was positioned in <50 μm to the stone surface. This was located in a basin filled with water, which was moved horizontally with the stone at constant velocity by a computer-controlled translation stage. The ablation rate and the ablation efficiency were determined by subsequent measurement of the depth and width of the resulting crater. The experiments were performed with varying parameters of the novel pulse regime and, for comparison, with standard laser settings. The experiments show significant differences in bubble dynamics and shape, depending on the temporal pulse regime. Lowest values for propulsion were measured for the standard pulse regime. The measured and calculated values for ablation depth, -rate and -efficiency are comparable for all investigated pulse regimes. Especially the ablation efficiency is quite high compared to values which were calculated from published data. In conclusion, these preliminary results show a high potential of the diode pumped Tm:YAG laser with novel laser driver for variable and high efficient lithotripsy. The wide range of available peak power should allow fragmentation as well dusting with the same laser system.

Ureteroscopic stone dusting utilizing a high power laser system has become more popular in recent years due to the production of finer debris/remains, lower retropulsion, and shorter operation time (potential to avoid the routine use of post-operative stenting and the use of ureteral access sheaths (UAS)). Typical dusting settings are lower pulse energy (as low as 0.2 J) with higher frequency (up to 80 Hz). This study investigates the best dusting mode to produce a high ablation rate and low retropulsion. The objective of the study was to evaluate the performance of a concept optimal dusting mode. In vitro investigations of Ho:YAG laser-induced stone ablation and retropulsion were performed with a benchtop model in a highly reproducible manner using a hands-free setup and measuring the effects of multiple pulses. A systematic comparison of the performance (ablation and retropulsion) of the concept optimal dusting mode against a reference laser dusting mode was conducted. Within this benchtop test model, the optimal dusting mode had a relatively fast ablation rate while keeping retropulsion low.

Laser lithotripsy is performed in a hospital operating room at high cost. Many lower ureter stones could potentially be treated in a less expensive, office-based procedure, if smaller ureteroscopes were available. Thulium fiber laser lithotripsy enables use of smaller (50-150-µm-core) optical fibers than Holmium:YAG laser lithotripsy, saving cross-sectional space within the working channel for exploitation in developing smaller ureteroscopes. A prototype, miniature, flexible, 40k digital ureteroscope tip was tested. Calibration, lighting, imaging, saline irrigation rate studies, and saline temperature safety studies were performed using a porcine ureter model, ex vivo.

The Ho:YAG laser has been the favored lithotripter for treating urinary calculus since shortly after its introduction in the 1990s because it can fragment all calculus compositions and produces less calculus migration (retropulsion) during treatment than the short-pulsed lasers. Although the lamp-pumped Ho:YAG laser has been commercialized for ureteroscopic laser lithotripsy (URS) for almost 25 years, the lamp-pumped laser rod's transient thermal behavior under an out-of-control lamp discharge has not been reported. A safety question arises: how big is the laser output under an out-of-control lamp discharge? The objective of this study is to simulate the transient thermal behavior of the lamp-pumped laser rod. The temperature profile inside the laser rod is transformed into an equivalent thermal lens, and from the time interval of the variation of the thermal lens between the lasing threshold and the maximum value of the stable region, we can estimate the level of the laser output. The simulation tool used for this study is the Ansys Fluent. The transient thermal behavior of the lamp-pumped laser rod under an out-of-control lamp discharge was reported. Optimization of the pumping pulse for the desired laser output pulse is for future study.

The flexibility of laser fibers is an important feature, especially for laser fibers intended to be used for laser lithotripsy procedures. The ability to navigate through the kidney’s tortuous anatomy using a flexible ureteroscope is critical for locating and fragmenting stones. With no previous research found on the topic, this study investigates the effects of power transmission on laser fiber stiffness during lithotripsy. Using a force gauge to hold a 365 μm core laser fiber at a 1.8 cm bend diameter, power transmission testing was done at 20, 40, 60, 80, and 100 W. Results from the force gauge show a strong positive correlation between the power transmission and the fiber stiffness (r=0.954, p=0.000). The momentum of photons has not been measured previously using this novel method or at power settings this low. Though the maximum change in stiffness (0.8 gf) contributed little to the laser fiber’s overall stiffness (64 gf), the results have applications across the photonics industry as the results show a link between power transmission and changes in optical fiber stiffness.

Early and accurate detection of neoplastic changes remains a critical challenge in bladder cancer diagnosis and treatment. Using existing cystoscopy guided techniques, direct visualization of the tumor is limited to the surface of the bladder. Assessment of sub-surface three-dimensional (3D) tumor extension and sub-surface tumor margin is a challenge. In our study, we developed a laparoscopic optical coherence tomography (OCT) imaging platform based on a rigid Gradient Index (GRIN) lenses (diameter ~ 4.5 mm) for imaging subsurface bladder tissues. Bladder tissues from UPII-SV40T mice models were imaged by this system ex vivo and algorithm was developed to quantify sub-surface tumor extension.