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This PDF file contains the front matter associated with SPIE Proceedings Volume 12817, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.
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Lasers and Light Sources for Therapy and Diagnosis I
The use of laser therapy in urology against cancer, such as bladder and prostate, has been increasing because of its advantages of minimally invasiveness and high accuracy.1 However, the maldistribution of optical energy can lead to unintended stimulation of cancer cells.2 Therefore, this study aims to investigate the stimulative effects of wavelength-dependent biomodulation on prostate cancer. Human-derived prostate cancer cell line DU145 was exposed to four different laser wavelengths (405, 532, 635 and 808nm) at a dose of 10J/cm2. After the laser irradiation, cell viability and ERK protein expression were assessed by using MTT assay and Western blot. For in vivo tests, DU145 xenograft models were used, and the tumors were extracted for histological analysis after ten days of volume monitoring. Among the wavelengths, the 808nm laser consistently increased cell viability by up to 21% for 24, 48, and 72 hours after the irradiation, compared to the control. The ERK protein expression was promoted by the irradiation of 405 and 808nm laser light. The in vivo tests showed that the 808nm laser significantly increased relative tumor volume (V/V0) up to 150% while the control group increased V/V0 up to 45%. Immunohistochemistry (IHC) staining of the sectioned tumor represented that VEGF and HIF-1a expression were induced after the exposure to the 808nm laser light. The current findings showed that depending on the wavelength, low level laser irradiation may affect the proliferation of prostate cancer cells, stimulating the tumor growth in the tumor microenvironment.
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Infrared (IR) lasers are being tested as an alternative to radiofrequency (RF) and ultrasonic (US) devices for hemostatic sealing of vascular tissues. In recent studies, a side-firing optical fiber was reciprocated, producing a linear laser beam pattern for sealing blood vessels. Challenges include limited field-of-view of vessel position within the device jaws, and matching fiber scan length to vessel size. A transparent jaw may improve visibility and enable custom treatment. Quartz and sapphire square optical chambers (2.7 x 2.7 x 25mm OD) were tested with a 1470nm laser and 550-μm-core fiber. Peak temperatures and cooling times were recorded on chamber surfaces. Angle polished fiber tips delivered 94% of light at a 90° angle. Porcine renal arteries with diameters of 3.4±0.7mm (n=13) for quartz and 3.2±0.7mm (n=14) for sapphire (P>0.05), were sealed using 30W for 5s. Reflection losses were 3.3% and 7.4% for quartz and sapphire. Peak temperatures on external chamber surface averaged 74±8 °C and 73±10 °C (P>0.05). Times to cool down to 37 °C measured 13±4s and 27±7s (P<0.05). Vessel burst pressures (BP) averaged 883±393mmHg and 412±330mmHg (P<0.05). For quartz, 13/13 (100%) vessels were sealed (BP>360mmHg), versus 9/14 (64%) for sapphire. Quartz provided more consistent seals and shorter cooling times than sapphire.
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For decades the need for organs for transplantation by far exceeds their availability, costing the lives of patients in desperate need for a transplant. This need has acted as driving force for the growth of the tissue engineering field. For the most part, tissue engineering utilizes scaffolds made of decellularized tissues or synthetic and natural hydrogels that can be polymerized. More recently, bioprinting has emerged as a robust alternative for precise placing of cells onto scaffolds or into polymers. Laser bioprinting, in particular, allows high speed and precise printing of cells into any bioink and with high viability. In this study, we use laser bioprinting to engineer urinary bladder tissue for regenerative medicine applications. Using a natural hydrogel and primary smooth muscle cells and urothelial cells, we have managed to print ex vivo bladder explants which recapitulate the structure of native urinary bladder.
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Stress urinary incontinence (SUI) is the involuntary leakage of urine during physical activity caused by bladder pressure exceeding urethral closure pressure. Slings are commonly used as a surgical treatment for SUI. However, the sling procedure is invasive and inserted into the body, resulting in mesh infection and chronic pain. The current study aims to evaluate the feasibility of laser treatment for SUI by using 980nm laser light with a balloon-integrated diffusing applicator as a minimally invasive and non-permanent procedure. A female porcine urethra was dilated using a balloon, and then the tissue was irradiated with the 980nm laser at 20W for 15s. The laser irradiated urethra were harvested 0, 14 and 28 days after the laser irradiation, respectively. Both Masson’s trichrome and Sirius red staining were applied to confirm structural changes and collagen distribution. There was no change in mucosal thickness between the laser irradiation group and the control group. In the laser irradiation group, the thickness of the muscle layer increased by approximately 35%, compared to the control group. Furthermore, the laser irradiation group showed a 30% increase in collagen distribution in the external urethral sphincter compared to the SUI model. The current study demonstrated the feasibility of the therapeutic effect of the 980nm laser in the porcine urethra. To confirm the safety and efficacy of the proposed photothermal treatment, we will conduct in vivo studies to assess the extent of nerve damage and molecular changes using PCR assays in chronic and disease-induced animal models.
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Lithotripsy with a Holmium laser is painless using an optical fiber catheter in the urinary tract with a minimally invasive surgical procedure. A video clip of the lithotripsy of the urinary stone phantom was obtained using a high-speed camera, and the lithotripsy results were visually evaluated. This result shows that precise lithotripsy is possible by multiple laser pulses by using the developed Holmium medical laser system.
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Lasers and Light Sources for Therapy and Diagnosis II
The urology field's workhorse for both soft tissue and stone removal has been the flashlamp-pumped CTH:YAG or Ho:YAG (Cr3+, Tm3+, Ho3+) triple doped yttrium aluminum garnet laser for over twenty years. The transient pressure field profile of the vapor bubbles produced by laser pulses provides key insight for understanding kidney stone ablation and retropulsion. The goal of this study is to evaluate the transient pressure field profile of the vapor bubbles in water produced by the laser modes of a Ho:YAG laser. A hydrophone measures the transient pressure field from the laser lithotripsy fiber tip at various locations. Based on the symmetry of the device and environment, the transient pressure field ellipsoid can be constructed with the measurement results. The transient pressure field profiles are significantly different across the standard laser modes.
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Photothermal therapy (PTT) has been studied as a minimal-invasive and effective treatment for prostate cancer. However, PTT has disadvantages, such as inadequate treatment and severe thermal injury to normal tissue. In this study, PTT was conjugated with photodynamic therapy (PDT) to improve treatment effect by covering untreated region of PTT and targeting specific cancer tissue. For PTT-PDT, 808nm laser was irradiated at 0.8W/cm2 for 5 min. To evaluate the experimental conditions, MTT, ROS assay, and annexin V-FITC/PI staining were conducted in in vitro tests. DU145-bearing mice models were treated and monitored for two weeks to confirm the feasibility of PTT-PDT. Then, histological and protein expression level were analyzed. As a result, PTT-PDT showed a steadily decreasing survival rate for 24 hr with a lower viability due to two types of cell death (necrosis and apoptosis) after the immediate necrosis. In the in vivo tests, PTT-PDT showed the lowest tumor growth rate for monitoring a 24% wider therapeutic area, compared to PTT. In addition, the apoptosis-related protein expression of PTT-PDT was more than 55% higher than PTT. In conclusion, the current study demonstrated that PTT-PDT enhanced therapeutic effect by complementing the incompletely treated region of PTT through the distant apoptosis of PDT. For clinical applications, further studies will be conducted to analyze the post-treatment of PTT-PDT and to improve the selectivity of photosensitizers.
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Previous benchtop studies demonstrated infrared (IR) laser sealing and cutting of blood vessels, in a sequential, two-step approach. This study describes a smaller, laparoscopic device design, and simultaneous approach to sealing and bisection of vessels. A 1470-nm IR laser sealed and bisected 40 porcine renal arteries, ex vivo. A reciprocating, side-firing, optical fiber, housed in a transparent square quartz optical chamber (2.7 x 2.7 x 25mm OD), delivered laser energy over an 11mm scan length, with a wide range of powers (41 to 59W) and treatment times (5 to 21s). Vessel diameters ranged from 2.5 to 4.8mm. All vessel cut ends were successfully sealed (80/80), as indicated by burst pressures greater than 360mmHg. The highest power, 59W, resulted in short times of 5 to 6s. Peak temperatures on the external chamber surface reached 103 °C. Time to cool down to body temperature was 37s. Infrared lasers simultaneously sealed and bisected blood vessels, with treatment times comparable to, and temperatures and cooling times lower than conventional devices.
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To assess efficacy, efficiency, and safety in holmium laser enucleation of the prostate (HoLEP), we directly compared intraoperative performance, postoperative outcomes, and safety in the original three-lobe enucleation technique with the more recent en-bloc method. Retrospective, propensity score-matched analysis of 606 men who underwent HoLEP for LUTS/BPO. Patients were stratified by technique, and groups were compared for perioperative parameters, safety, and short-term functional outcomes. While postoperative symptoms and urodynamic parameters improved irrespective of technique, we report significantly less adverse events (Clavien-Dindo classification >/=II vs < II) for patients receiving en-bloc enucleation. Additionally, en-bloc enucleation was more efficient i.e., less than half of total laser energy (kJ), twice shorter enucleation time, and surgical performance (g/kJ/min) significantly increased 4-fold with prostate volume, compared to three-lobe enucleation. While HoLEP in general is a safe and effective procedure, en-bloc enucleation techniques offer better surgical performance.
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Endoscopic camera sensors nowadays can adjust the image illumination not only through gain and exposure time but also LED illumination with adjustable illumination power. The LED based method is very responsive in adjusting the illumination but may introduce over-compensation issue when interfering with external light source, such as the aiming beam during lithotripsy procedure. This paper proposed a new light control algorithm that handles the interference of the external light source.
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Early and accurate detection of renal tumor malignancy remains a critical challenge in clinical cancer diagnosis and treatment. Unfortunately, a third of all patients aren’t diagnosed until they have advanced disease. Percutaneous renal biopsy (PRB) followed by histopathology is the most commonly used surgical procedure for early kidney detection and diagnosis. However, PRB is challenging in precisely recognizing the tumor tissue and avoiding renal hemorrhage. In this project, we developed an endoscopic polarization-sensitive optical coherence tomography (PS-OCT) probe for PRB guidance. Deep-learning method was used to automate the tumor recognition procedure.
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We propose a workflow to design a metalens for a double-path fiber-optic endoscope application. The metalens is made of optical subwavelength scatterers (~106-108 meta-atoms) characterized individually with the Rigorous Coupled Wave Analysis (RCWA) method. They can collectively manipulate the phase, amplitude, and polarization of incident light. The response of the full metalens is reconstructed from the response of each individual unit cell according to a target phase profile optimized in ray-tracing optics software. Image acquisition with the full system is simulated in physics-based ray-tracing software with an ideal metalens and simulation-based fiber illumination in a 3D blood vessel environment.
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We present a novel sensor system based on the principles of triangulation and elastography that allows intraoperative, endoscopic and non-contact acquisition of elastic tissue properties. The sensor system consists of a 3D-printed fiber-based fringe projector, a force application system to deform the tissue, and an endoscope that records the tissue deformation at a triangulation angle. This allows reconstruction of depth maps and the elastic behavior of the specimen. The measurement system is designed to be used during cystoscopy or transurethral bladder tumor resection and can be integrated into the working channel of a commercially available cystoscope.
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End-stage renal disease (ESRD) is a serious medical condition characterized by an irreversible decline in kidney function. The optimal treatment for ESRD is kidney transplantation, providing improved quality and quantity of life and lower mortality rates compared to other treatments. While there exists a vast constellation of variables that contribute to the ultimate success of a kidney transplant, timely diagnosis of allograft dysfunction and its underlying etiology is crucial in informing appropriate treatment plans and improving graft survival rates. The monitoring and diagnosis of early postoperative allograft function may involve regular bloodwork for renal function testing, percutaneous kidney biopsy, and intermittent transabdominal ultrasonography, all of which have inherent limitations and risks. Objective intraoperative assessment of graft quality and perfusion characteristics lacks reliable and safe techniques in kidney transplantation. We propose applying a novel optical technique based on near-infrared imaging (NIRI) for intraoperative interrogation of allograft metabolic function. The objectives of this study were to examine the feasibility and functionality of a non-contact, non-invasive, handheld NIRI device for intraoperative monitoring of graft hemodynamics and oxygenation during transplantation. Intraoperative NIRI assessment of the kidney parenchyma tissue oxygen saturation (StO2) was performed for 25 transplants. Images of the allograft were taken at the back table after preparation, in-situ before perfusion, at the earliest convenience after reperfusion, and then at 1, 2, 3, 4, 5, 10, 15, 20, and 25 minutes following reperfusion. A final image was taken before closure. The kidney parenchyma tissue was digitally segmented and the average parenchymal StO2 was calculated at each time point. All patients showed low StO2 in the images taken before reperfusion, with an increase in StO2 seen after clamp removal. Our study demonstrated the feasibility and functionality of a handheld NIRI device for intraoperative monitoring of kidney graft hemodynamics and oxygenation during transplantation. For future studies, clinical measures, and additional hemodynamic parameters, such as the velocity in reaching max StO2, will be compared for donor kidneys of varying quality.
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It is necessary to develop an objective diagnostic technique to examine the sexual dysfunction of female patients who are afflicted with the disorders. For this purpose, we developed a combined DRS and DCS probe to measure the change of oxy-, deoxy-, and total hemoglobin concentration along with blood flow from the vaginal wall of female rats. Vaginal oxygenation, blood flow, and temperature were continuously monitored before and after sexual arousal induced by apomorphine. The hemodynamic information achieved by the probe can be utilized to establish an objective and accurate standard for the diagnosis of female sexual disorders.
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Cystoscopy is a common diagnostic procedure for hematuria evaluation, bladder cancer surveillance, and guidance for resection of suspicious bladder lesions. Similar to other endoscopic procedures, standard white light cystoscopy is limited by diagnostic accuracy, image quality, and operator dependency. Artificial intelligence is emerging as a potential tool for clinical decision support for endoscopy and endoscopic surgery. However, current deep learning methods for cystoscopy are based on highly curated individual images and do not consider the temporal correlation among the frames within a video sequence, thereby limiting their performance in real world clinical settings. Herein we propose SEQ-3D, a sequential deep learning model for cystoscopic video analysis that considers both the short- and long-range relationships among the frames and the spatial information in each frame. Model validation was performed using a benchmark cystoscopy video dataset derived from 60 patients and 163 pathologically confirmed bladder regions of interest (ROI) consisted of representative cancerous bladder tumors and cancer-mimicking benign lesions. The full-length videos (216,870 frames) were annotated by expert clinicians and divided into distinct frame sequences defined as scenes. SEQ-3D outperforms existing sequential deep learning methods and achieved a per-ROI accuracy of 100%, per-scene sensitivity of 93.1%, and per-scene specificity of 83.3%, exhibiting balanced performance at detecting a wide variety of bladder ROI. Our findings are promising for deployment in prospective clinical settings and can be extrapolated to endoscopic applications in other organ systems.
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High fluid temperatures have occurred in studies with laser lithotripsy, yet temperature within the renal parenchyma has not been well characterized. Our objective was to measure renal tissue temperatures during laser activation in a calyx. Ureteroscopy was performed in porcine subjects with a prototype ureteroscope containing a temperature sensor at its tip. A needle with thermocouples was introduced percutaneously to allow temperature measurement in the renal medulla and cortex. Trials of 60 second laser activation (40 W) were conducted with irrigation of 8 ml/min. Substantial temperature elevation was observed in the renal medulla with thermal dose in two of nine trials exceeding threshold for tissue injury. In conclusion, high-power laser settings (40 W) can induce potentially injurious tissue temperatures in the in-vivo porcine model, particularly in the region adjacent to the collecting system.
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Laser lithotripsy destroys urinary stones by ablating them into fine particles and dust. However, the nature of the resulting dust is not well understood, nor how this differs for different stone types. To investigate this, canine stones of different types were ablated in vitro using a Ho:YAG laser and the resulting particles analysed to calculate a characteristic particle size distribution for each stone type. Differences in these size distributions may require the resulting stone dust to be managed differently in vivo.
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Recent studies suggest that cavitation effect following laser induced vapor bubble collapse is more dominant than the photothermal effect in stone ablation during laser lithotripsy. Our research aims to introduce an experimental study design that precisely measures each effect's contribution using gypsum phantom stones. To isolate the cavitation-only mechanism after the collapse of the laser-induced vapor bubble, a phantom stone was submerged in a dye solution. The dye solution absorbed all laser light, generating cavitation, with additional experiments confirming the absence of any photothermal effect when the dye was not used. The fiber was positioned both parallel to the stone surface and perpendicular at a 1mm distance, exposing it solely to cavitation. In another set of experiments, a phantom stone was submerged in water and 2μm light from a thulium yttrium aluminum garnet (Tm:YAG) laser was delivered via the same optical fiber positioned (this time) perpendicular to the stone surface. In this case, both optical absorption and cavitation effect from laser-induced vapor bubble collapses were observed but the measured pressure transients showed significantly lower peak pressures compared to the first set. In a final set of experiments, these conditions remained constant, except the fiber was positioned parallel to the stone surface, once again exposing it to only the cavitation from the collapse of the laser induced vapor bubble. Craters created by all methods were imaged using an optical coherence tomography (OCT) system. Measured volumes showed that stone ablation was dominated by photo-thermal, and not by cavitation from the vapor bubble collapse. In fact, in two of the three trials of stone experiments (n=5, each trial) that were subjected to cavitation-only, there was no observable ablation. One trial produced an average volume that was 50% smaller than the average resulting from a single photo-thermal-only case (p = 0.0022 < 0.05). Our results suggest that finetuning of lithotripsy procedures with focus on energy transmission to the stone can provide optimal results.
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When light is scattered, fog forms over transparent surfaces, causing blurry vision. This could pose a problem for clinical applications, particularly with endoscopes. Predicting the clinical result during diagnosis can be challenging due to blurry vision in the image. The diagnosis of gastrointestinal disorders, including colon illnesses, may be enhanced by the development of high-resolution, fog-free endoscopes. There hasn't been much research done in this field, though. Transparent surfaces with dual-purpose antibacterial and antifog coatings have several uses in the medical field. Coatings having such dual functional characteristics have been the subject of relatively few reported studies. In this work, a dip coating technique was used to manufacture the Fe-doped tannic acid (TA-Fe) integrated polyvinyl alcohol (PVA) coating (TA-Fe@ PVA) with antibacterial and antifogging capabilities. SEM and UV-visible spectroscopy were used to characterize the produced coating, and then its antibacterial, antifogging, and biocompatibility properties were assessed. The transmission spectra for the TA-Fe@PVA coating (>95%) demonstrate good transparency in the visible region (370 to 700nm), suggesting that it can be used in antifogging applications. The bacterial suspensions against S. aureus and E. coli may be effectively reduced by the presence of TA-Fe in the PVA. The hydroxyl group in PVA allowed for the realization of the antifogging performance. Furthermore, the coating exhibited favorable cytotoxicity behavior. According to the preliminary study results, the produced coating shows promise for use in endoscopic applications.
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