Pei Zhong

Abstract Urinary stone disease is a common urological condition with increasing incidence, particularly in developed countries. Laser lithotripsy (LL) has become a preferred minimally invasive treatment due to its high precision and low tissue damage. Recent studies suggest that cavitation plays a critical role in stone damage during LL, and three-dimensional passive cavitation mapping (3D-PCM) has emerged as a promising tool for detecting these events. However, clinical translation of 3D-PCM remains challenging due to limitations in imaging depth, field of view (FOV), and procedural compatibility. Here, we present a large-FOV dual-modality imaging system (3D-PCM and B-mode ultrasound) based on a large-aperture planar ultrasound array. Through array optimization and model-based reconstruction, our system achieves an expanded FOV of ∼40 × 40 mm 2 at a clinically relevant imaging depth of ∼110 mm, while maintaining high spatial resolution of ∼0.6 mm laterally and ∼0.4 mm axially. In vivo experiments in a porcine model demonstrate that the reconstructed cavitation distribution correlates well with stone damage. Our technology has the potential to provide real-time treatment feedback during LL without disrupting the standard workflow.

Background:Familial exudative vitreoretinopathy (FEVR) is a rare inherited ocular disorder characterized by abnormal peripheral retinal vascular development. KIF11 variants are known to cause autosomal dominant FEVR, but novel pathogenic variants remain to be identified. Objective:This study aimed to identify a novel causative variant of FEVR and provide evidence for genetic counseling. Methods:Whole-exome sequencing was performed on members of a Chinese family with FEVR. Rare variants with a gnomAD allele frequency <0.1% in East Asian and general populations were prioritized. Sanger sequencing was used for validation, and bioinformatic analyses (including Combined Annotation Dependent Depletion [CADD] score and cross-species conservation analysis) were conducted to assess pathogenicity. Results:A novel heterozygous frameshift variant KIF11 c.1239_1240del (p.V414Sfs*9) was identified in the proband, his brother, and his mother. This variant, absent from public databases (1000 Genomes, ExAC, gnomAD), had a CADD score of 26.9 and affected a highly conserved residue, suggesting disruptive effects on protein structure. The proband’s mother showed macular involvement. Conclusions:The novel KIF11 frameshift variant (c.1239_1240del p.V414Sfs*9) identified in a Chinese family expands the mutation spectrum of autosomal dominant FEVR, with macular involvement aiding clinical prognostic assessment.

Urinary stone disease, characterized by the hard mineral deposits in the urinary tract, has seen a rising prevalence globally. This condition often leads to severe pain and requires medical intervention. Laser lithotripsy, a minimally invasive treatment, uses laser to fragment urinary stones to facilitate removal or natural passage. Among available laser technologies, Ho:YAG laser has established itself as the gold standard for three decades. Efforts to improve ablation efficiency have focused on laser parameters such as pulse energy and frequency. This study introduces an ablation enhancement strategy that incorporates nanoparticles with strong near-infrared absorption into the surrounding fluid to enhance light-matter interaction. Using 0.03 wt.% PEDOT:PSS nanofluid improves stone ablation efficiency by 38-727% in spot treatment and 26-75% in scanning treatment with a clinical Ho:YAG laser lithotripter. The highly absorbing nanofluid accelerates vapor tunnel formation, boosts laser energy transmission, and permeates stone pores to enhance damage, without increasing thermal tissue injury. Cytotoxicity tests also confirmed minimal toxicity at appropriate concentrations. This nanofluid-based approach offers a promising advancement for more efficient and safer laser lithotripsy. Further work should address the remaining challenges for clinical translation, including aggregation in saline, efficacy in real human kidney stones, and comprehensive animal studies.

The purpose of the article is to establish a point that the three-level musical inheritance mechanism, formed in the course the cultural and civilizational genesis of China, reflects theaesthetic paradigm of the continuity of folk music culture, complimentarily combining ‘ancient’ and ‘new’, tradition and innovation. The novelty of the article is to substantiate the ethical boundary between the ancient Chinese musical tradition and the modernization processes in the field of modern folk music practices. As a result, the authors formulate main conclusions of the study, showing that today, at the stage of modernizing China, this inheritance mechanism remains an integral part of family "music education", being considered as an important factor in state cultural policy and being part of China's national strategy. However, under the conditions of the New China, it undergoes certain transformations, partly related to the phenomenon of "cultural borrowing" in Chinese musical and educational discourse.

Objectives: To investigate the fracture mechanism of impacted ureteral stones during laser lithotripsy (LL). Materials and Methods: Impacted 6 x 6 mm cylindrical BegoStone samples embedded in a hydrogel ureter model were treated using either Holmium:YAG (Ho:YAG) laser or Thulium Fiber Laser (TFL) via three clinical strategies: "drill and core", contact, and non-contact modes. Laser pulses were delivered using three pulse energy/frequency settings: 0.8 J/12 Hz, 1.0 J/10 Hz, and 1.2 J/8 Hz with a 3 s on/3 s off protocol, under continuous irrigation at 40 mL/min. Crater formation, surface crack development, and bubble dynamics were assessed via optical coherence tomography, video, and high-speed photography. To delineate the contributions of different plausible damage mechanisms, bubble collapse was suppressed by leveraging the ureteroscope's proximity effect, and thermal ablation was minimized by treating donut-shaped stones with a central tunnel. The role of bubble expansion in stone fracture was further evaluated by systematically varying tunnel size or pulse energy. Results: Surface cracks and stone fracture were observed exclusively in Ho:YAG laser-treated stones using the "drill and core", but not the other two strategies. TFL produced deeper craters yet failed to induce any significant crack formation or propagation under all conditions. Suppression of bubble collapse or thermal ablation had minimal effect on surface crack formation and growth. In contrast, the extent and number of surface cracks correlated strongly with the maximum lateral diameter and expansion rate of the vapor bubbles - two parameters that were significantly greater for Ho:YAG laser than TFL. Importantly, the crack formation also showed an inverse correlation with the size of the initial crater or tunnel in the stone. Conclusion: Intra-crater bubble expansion, rather than thermal ablation or bubble collapse, is the primary mechanism driving the fracture of impacted ureteral stone in LL.

Objective: To optimize thulium fiber laser (TFL) settings for effective stone fragmentation although minimizing thermal injury in confined ureteral spaces using a three-dimensional ureter model. Materials and Methods: A hydrogel-based ureter model was maintained at 37.2 ± 0.5°C, with a cylindrical BegoStone (10 × 10 mm, 1.00 ± 0.07 gm) occluding the ureter. Ureteroscopy was performed using a 150 µm TFL fiber for 3 minutes with room temperature irrigation and differing rates (0, 20, 40 mL/min) and power settings (6.4 to 20 W). Maximum sustained temperature (MST) and cumulative thermal dose (cumulative equivalent minutes at 43°C) were assessed against a 120-minute safety threshold. We also evaluated the effects of ureter volume and irrigation temperature. Stone mass treated was calculated by subtracting the mass of residual fragments &gt;3 mm from the initial mass. Results: At 6.4 and 10 W, MSTs were below body temperature, and thermal doses were under 1 minute, indicating minimal thermal risk. At 20 W with 20 mL/min irrigation, MST exceeded 43°C within seconds, and thermal doses surpassed 120 minutes. Treatment efficiency was highest at 20 W (1.58 mg/s), followed by 10 W (1.15 mg/s) and 6.4 W (0.78 mg/s). Among 10 W settings, 1.0 J/10 Hz was more efficient than 2.0 J/5 Hz and 3.0 J/3 Hz. Safe settings produced 95.5% fine dust, whereas high-energy pulses 2–3 J produced significantly more fragments (1–3 mm) compared with settings with pulse energy 0.5–1.0 J. Increasing irrigation to 40 mL/min or using 15°C irrigation effectively reduced MST and improved efficiency, particularly at 20 W. Conclusion: Our study demonstrates the risk of thermal injury with 20 W TFL treatment. Conversely, 10 W settings at 2.0 J/5 Hz are safe and effective for fragmentation. Future research will focus on validating these optimal settings for human stone treatment.

This case report describes orthodontic treatment of an adult female with severe skeletal Class II malocclusion on a Class II skeletal base complicated by deficient chin, condylar resorption and anterior open bite (The IOFTN score = 4.4, ANB °=11.3, SN-MP °=58.2). Treatment carried out with 4 1st premolar extractions and using two mini-implants (diameter: 1.6 mm; length: 10 mm; Cibei Medical Instruments, Ningbo, China) that were inserted between the maxillary first molar and second premolar to intrude the bilateral maxillary first molars using elastic traction. Alveolar bone dehiscences were detected on the palatal or lingual side of the anterior teeth roots after orthodontic camouflage treatment. During the 3-year follow-up period, acceptable periodontal health and favourable alveolar bone modeling of maxillary and mandibular anterior teeth were detected. No further lesions developed in the condyle during the treatment period. This case confirmed that the capacity of palatal or lingual alveolar bone remodeling, which might be greater than previously believed, but the specific mechanism is still unclear.

Vapor bubbles produced by long-pulsed laser often have complex non-spherical shapes that reflect some characteristics of the laser beam. The transition between two commonly observed shapes - namely, a rounded pear-like shape and an elongated conical shape - is studied using a new computational model that combines compressible multiphase fluid dynamics with laser radiation and phase transition. Two laboratory experiments are simulated, in which Holmium:YAG and Thulium fiber lasers are used respectively to generate bubbles of different shapes. In both cases, the predicted bubble nucleation and morphology agree reasonably well with the experimental observation. The full-field results of laser irradiance, temperature, velocity, and pressure are analyzed to explain bubble dynamics and energy transmission. It is found that due to the lasting energy input, the vapor bubble's dynamics is driven not only by advection, but also by the continued vaporization at its surface. Vaporization lasts less than 1 microsecond in the case of the pear-shaped bubble, compared to over 50 microseconds for the elongated bubble. It is thus hypothesized that the bubble's morphology is determined by a competition. When the speed of advection is higher than that of vaporization, the bubble tends to grow spherically. Otherwise, it elongates along the laser beam direction. To test this hypothesis, the two speeds are defined analytically using a model problem, then estimated for the experiments using simulation results. The results support the hypothesis. They also suggest that when the laser's power is fixed, a higher laser absorption coefficient and a narrower beam facilitate bubble elongation.

Kidney stone disease is a major public health issue. By breaking stones with repeated laser irradiation, laser lithotripsy (LL) has become the main treatment for kidney stone disease. Laser-induced cavitation is closely associated with stone damage in LL. Monitoring the cavitation activities during LL is thus crucial to optimizing the stone damage and maximizing LL efficiency. In this study, we have developed 3-D super-resolution passive cavitation mapping (3D-SRPCM), in which the cavitation bubble positions can be localized with an accuracy of m, which is 1/10th of the acoustic diffraction limit. Moreover, the 3D-SRPCM reconstruction speed has been improved by 300 times by adopting a GPU-based sparse-matrix beamforming approach. Using 3D-SRPCM, we studied LL-induced cavitation activities on BegoStones, both in free space of water and confined space of a kidney phantom. The dose-dependent analysis provided by 3D-SRPCM revealed that accumulated impact pressure on the stone surface has the highest correlation with the stone damage. By providing high-resolution cavitation mapping during LL treatment, we expect that 3D-SRPCM may become a powerful tool to improve the clinical LL efficiency and patient outcome.

Urinary stone disease, characterized by the formation of hard mineral deposits in the urinary tract, has seen a rising prevalence in the U.S. in recent years. This condition often leads to severe pain and typically requires medical intervention. Laser lithotripsy, a minimally invasive treatment, uses laser energy to fragment urinary stones into smaller pieces, facilitating easier removal or natural passage. Among available laser technologies, the holmium:yttrium-aluminum-garnet (Ho:YAG) laser has established itself as the gold standard over the past three decades. Efforts to improve Ho:YAG laser ablation efficiency have largely focused on adjusting laser parameters such as pulse energy and frequency. In this study, we proposed a nanoplasmonic engineering strategy by incorporating nanoparticles (NPs) with strong near-infrared (NIR) absorption into the fluid surrounding the stone, enhancing the light-matter interaction. Using a 0.03 wt.% PEDOT:PSS nanofluid, stone ablation efficiency improved by 38-727% in spot treatment and 26-75% in scanning treatment with a clinical laser lithotripter. The highly absorbing nanofluid accelerates vapor tunnel formation, boosts laser energy transmission to the stone, and permeates stone pores to enhance damage, without increasing thermal tissue injury risk. Cytotoxicity tests also confirmed minimal toxicity at appropriate concentrations. This nanofluid-based approach offers a promising advancement for more efficient and safer laser lithotripsy.

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP63)1 May 2024MP63-03 INVESTIGATING OPTIMAL SETTINGS AND THERMAL INJURY RISK OF THE THULIUM FIBER LASER IN AN ANATOMICAL KIDNEY MODEL Ezra J. Margolin, Arpit Mishra, Robert A. Medairos, David L. Barquin, Junqin Chen, Francois Soto-Palou, Jodi Antonelli, Glenn M. Preminger, Charles D. Scales, Gary J. Faerber, Pei Zhong, and Michael E. Lipkin Ezra J. MargolinEzra J. Margolin , Arpit MishraArpit Mishra , Robert A. MedairosRobert A. Medairos , David L. BarquinDavid L. Barquin , Junqin ChenJunqin Chen , Francois Soto-PalouFrancois Soto-Palou , Jodi AntonelliJodi Antonelli , Glenn M. PremingerGlenn M. Preminger , Charles D. ScalesCharles D. Scales , Gary J. FaerberGary J. Faerber , Pei ZhongPei Zhong , and Michael E. LipkinMichael E. Lipkin View All Author Informationhttps://doi.org/10.1097/01.JU.0001009436.52988.91.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite the increasing usage of the novel Thulium Fiber Laser (TFL), comprehensive evaluation of settings which maximize treatment efficacy while minimizing the risk of thermal injury is limited. We aim to identify the optimal laser settings for stone dusting while assessing the potential thermal injury risk associated with the TFL in an anatomical kidney model. METHODS: A 3D-printed anatomical kidney model, designed from human computed tomography scans, was used. A 6 x 6 mm cylindrical soft BegoStone was positioned in an upper pole calyx, and TFL lithotripsy was performed using a 200 µm fiber inserted through a flexible ureteroscope with continuous flow irrigation. The stone ablation speed (mg/s) of the complete treatment was evaluated across various pulse energy (Ep) (0.2 – 1.5 J), frequency (F) (6 to 150 Hz), and power settings (W) (10 W to 30 W). Additionally, temperature changes were recorded by placing multiple thermocouples near the tissue boundary, and the risk of tissue injury was determined by calculating the thermal dose as cumulative equivalent minutes at 43°C (CEM43°C). The experiments were timed from the start of treatment until completion, and the remaining BegoStone fragments were collected and weighed to calculate ablation speed. RESULTS: A total of 5 experiments were conducted for each setting, with an average initial stone mass of 259.57±13.21 mg. High-power settings exhibited the fastest ablation speed (Fig 1a). When power was controlled, increasing the Ep resulted in higher ablation speeds (Fig 1a). Ureteral thermal injury risk was observed with 20 W and 30 W power settings (Fig 1b), but not with the 10 W power settings. Lastly, the low Ep and high F combination led to faster temperature increases, reaching the thermal dose for tissue injury (t43=120 min) more rapidly than the high Ep / low F combination. CONCLUSIONS: High Ep, low F settings demonstrate maximum efficacy without excessive thermal toxicity for stone dusting using TFL. High power settings demonstrate considerable risk for possible thermal injury. Further studies are needed to accurately quantify the size of dust particles generated during ablation in these settings with different types of urinary stones. Download PPT Source of Funding: This project is supported by the National Institutes of Health (NIH) through grants 1P20DK135107-02 and 2R01DK052985-26 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1031 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ezra J. Margolin More articles by this author Arpit Mishra More articles by this author Robert A. Medairos More articles by this author David L. Barquin More articles by this author Junqin Chen More articles by this author Francois Soto-Palou More articles by this author Jodi Antonelli More articles by this author Glenn M. Preminger More articles by this author Charles D. Scales More articles by this author Gary J. Faerber More articles by this author Pei Zhong More articles by this author Michael E. Lipkin More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyStone Disease: Surgical Therapy (Including ESWL) V (MP78)1 May 2024MP78-04 EVALUATION OF CHAR FORMATION USING THE THULIUM FIBER LASER: THE STANDOFF BETWEEN HIGH VERSUS LOW PULSE ENERGY David L. Barquin, Junqin Chen, Arpit Mishra, Robert A. Medairos, Ezra J. Margolin, Jodi Antonelli, Glenn M. Preminger, Charles D. Scales, Gary J. Faerber, Pei Zhong, and Michael E. Lipkin David L. BarquinDavid L. Barquin , Junqin ChenJunqin Chen , Arpit MishraArpit Mishra , Robert A. MedairosRobert A. Medairos , Ezra J. MargolinEzra J. Margolin , Jodi AntonelliJodi Antonelli , Glenn M. PremingerGlenn M. Preminger , Charles D. ScalesCharles D. Scales , Gary J. FaerberGary J. Faerber , Pei ZhongPei Zhong , and Michael E. LipkinMichael E. Lipkin View All Author Informationhttps://doi.org/10.1097/01.JU.0001008856.05210.73.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Char formation on stones during laser lithotripsy with the Thulium Fiber Laser (TFL) can significantly impede treatment efficacy, especially in cases involving calcium phosphate (CaP) stones. The current understanding the reasons for char formation during TFL is limited. Our aim was to assess how char formation and treatment efficiency in a CaP stone may vary under various TFL settings. METHODS: A 6 x 6 x 4 cm 100% CaP stone was cold-mounted, bisected, and polished using 1200-grit sandpapers to create a flat surface (Figure 1a). The stone sample was fixed in a water tank filled with degassed water at room temperature and treated by the TFL at two different pulse energy/frequency settings with a power of 10 W: 0.2 J/50 Hz and 0.8 J/12 Hz. A 200 µm fiber was placed perpendicularly to the stone surface. Laser spot treatments were delivered at three different standoff distances (SD) (0.2 mm, 0.5 mm, 1 mm) and three different treatment times (TT) (1 sec, 2 sec, 3 sec). Each combination of SD and TT was repeated three times at a different localized area of the stone. The resultant stone crater volume was then quantified by optical coherence tomography. Charring was defined as the carbonization of stone materials (Figure 1b). Crater volumes were compared using Student's t-tests, and charring rates were compared using chi squared tests. The effects of SD and TT on crater volume were assessed using multivariable linear regression. RESULTS: Charring, was observed more frequently using the low pulse energy 0.2 J setting at all SDs compared to 0.8 J (all p<0.05). At the 0.2 J setting, charring was observed in 7/9 tests at SD 0.2 mm, 5/9 tests at 0.5 mm, and 4/9 tests at 1 mm. At the 0.8 J setting, charring was not observed in any tests at any SD. Crater volume was significantly greater at the 0.8 J setting at all SD and TT (all p<0.01, Figure 1c). At the 0.8 J setting, crater volume increased with higher TT (coef 0.18, p<0.001) and decreased with higher SD (coef -0.60, p<0.001). At the 0.2 J setting, crater volume only increased slightly with higher TT (coef 0.04, p<0.001) and did not change with higher SD (coef 0.01, p=0.564). CONCLUSIONS: At a low pulse energy and high frequency, TFL treatment efficiency of CaP stone may significantly decrease due to the charring. A high pulse energy level may help to avoid the charring and improve the treatment efficiency. Download PPT Source of Funding: This project is supported by the National Institutes of Health (NIH) through grants 1P20DK135107-02 and 2R01DK052985-26 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1264 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information David L. Barquin More articles by this author Junqin Chen More articles by this author Arpit Mishra More articles by this author Robert A. Medairos More articles by this author Ezra J. Margolin More articles by this author Jodi Antonelli More articles by this author Glenn M. Preminger More articles by this author Charles D. Scales More articles by this author Gary J. Faerber More articles by this author Pei Zhong More articles by this author Michael E. Lipkin More articles by this author Expand All Advertisement PDF downloadLoading ...

Objectives To explore the optimal laser settings and treatment strategies for thulium fibre laser (TFL) lithotripsy, namely, those with the highest treatment efficiency, lowest thermal injury risk, and shortest procedure time. Materials and Methods An in vitro kidney model was used to assess the efficacy of TFL lithotripsy in the upper calyx. Stone ablation experiments were performed on BegoStone phantoms at different combinations of pulse energy (E P ) and frequency (F) to determine the optimal settings. Temperature changes and thermal injury risks were monitored using embedded thermocouples. Experiments were also performed on calcium oxalate monohydrate (COM) stones to validate the optimal settings. Results High E P /low F settings demonstrated superior treatment efficiency compared to low E P /high F settings using the same power. Specifically, 0.8 J/12 Hz was the optimal setting, resulting in a twofold increase in treatment efficiency, a 39% reduction in energy expenditure per unit of ablated stone mass, a 35% reduction in residual fragments, and a 36% reduction in total procedure time compared to the 0.2 J/50 Hz setting for COM stones. Thermal injury risk assessment indicated that 10 W power settings with high E P /low F combinations remained below the threshold for tissue injury, while higher power settings (&gt;10 W) consistently exceeded the safety threshold. Conclusions Our findings suggest that high E P /low F settings, such as 0.8 J/12 Hz, are optimal for TFL lithotripsy in the treatment of COM stones. These settings demonstrated significantly improved treatment efficiency with reduced residual fragments compared to conventional settings while keeping the thermal dose below the injury threshold. This study highlights the importance of using the high E P /low F combination with low power settings, which maximizes treatment efficiency and minimizes potential thermal injury. Further studies are warranted to determine the optimal settings for TFL for treating kidney stones with different compositions.

Holmium:yttrium–aluminum-garnet (Ho:YAG) laser lithotripsy (LL) has been the treatment of choice for kidney stone disease over two decades, yet the mechanisms of action are not completely clear. Besides photothermal ablation, recent evidence suggested that cavitation bubble collapse is pivotal in kidney stone dusting when the Ho:YAG laser operates at low pulse energy (Ep) and high frequency (F). In this work, we perform a comprehensive series of experiments and model-based simulations to dissect the complex physical processes in LL. Under clinically relevant dusting settings (Ep = 0.2 J, F = 20 Hz), our results suggest that majority of the irradiated laser energy (>90 %) is dissipated by heat generation in the fluid surrounding the fiber tip and the irradiated stone surface, while only about 1 % may be consumed for photothermal ablation, and less than 0.7 % is converted into potential energy of the bubble at maximum expansion. We reveal that photothermal ablation is confined locally to the laser irradiation spot, whereas cavitation erosion is most pronounced at a fiber tip-stone surface distance about 0.5 mm where multi foci ring-like damage outside the thermal ablation zone is observed. The cavitation erosion is caused by the progressively intensified collapse of jet-induced toroidal bubble near the stone surface (<100 μm), as a result of Raleigh-Taylor and Richtmyer-Meshkov instabilities. The ensuing shock wave-stone interaction and resultant leaky Rayleigh waves on the stone surface may lead to dynamic fatigue and superficial material removal under repeated bombardments of toroidal bubble collapses during kidney stone dusting in LL.

Mechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, histotripsy is distinct from the conventional HIFU techniques resulting in hyperthermia and thermal injury. Phase I human trials have shown the initial safety and efficacy of histotripsy in treating patients with malignant liver tumors. In addition to tissue ablation, a promising benefit of M-HIFU has been stimulating a local and systemic antitumor immune response in preclinical models and potentially in the Phase I trial. Preclinical studies combining systemic immune therapies appear promising, but clinical studies of combinations have been complicated by systemic toxicities. Consequently, combining M-HIFU with systemic immunotherapy has been demonstrated in preclinical models and may be testing in future clinical studies. An additional alternative is to combine intratumoral M-HIFU and immunotherapy using microcatheter-placed devices to deliver both M-HIFU and immunotherapy intratumorally. The promise of M-HIFU as a component of anti-cancer therapy is promising, but as forms of HIFU are tested in preclinical and clinical studies, investigators should report not only the parameters of the energy delivered but also details of the preclinical models to enable analysis of the immune responses. Ultimately, as clinical trials continue, clinical responses and immune analysis of patients undergoing M-HIFU including forms of histotripsy will provide opportunities to optimize clinical responses and to optimize application and scheduling of M-HIFU in the context of the multi-modality care of the cancer patient.

Vapor bubbles generated by long-pulsed laser often have complex non-spherical shapes that reflect some characteristics (e.g., direction, width) of the laser beam. The transition between two commonly observed shapes - namely, a rounded pear-like shape and an elongated conical shape - is studied using a new computational model that combines compressible multiphase fluid dynamics with laser radiation and phase transition. Two laboratory experiments are simulated, in which Holmium:YAG and Thulium fiber lasers are used separately to generate bubbles of different shapes. In both cases, the bubble morphology predicted by the simulation agrees reasonably well with the experimental measurement. The simulated laser radiance, temperature, velocity, and pressure fields are analyzed to explain bubble dynamics and energy transmission. It is found that due to the lasting energy input (i.e. long-pulsed laser), the vapor bubble's dynamics is driven not only by advection, but also by the continuation of vaporization. Notably, vaporization lasts less than 1 microsecond in the case of the pear-shaped bubble, versus more than 50 microseconds for the elongated bubble. It is hypothesized that the bubble's shape is the result of a competition. When the speed of advection is higher than that of vaporization, the bubble tends to grow spherically. Otherwise, it elongates along the laser beam direction. To clarify and test this hypothesis, the two speeds are defined analytically using a simplified model, then estimated for the experiments using simulation results. The results support the hypothesis. They also suggest that a higher laser absorption coefficient and a narrower beam facilitate bubble elongation.

Objective: Low energy and high frequency settings are used in stone dusting for holmium lasers. Such settings may not be optimal for thulium fiber laser (TFL). With the seemingly endless combination of settings, we aim to provide guidance to the practicing urologists and assess the efficiency of the TFL platform in an automated in vitro “dusting model.” Materials/Methods: Three experimental setups were designed to investigate stone dusting produced by an IPG Photonics TLR-50 W TFL system using 200 μm fiber and soft BegoStone phantoms. The most popular 10 and 20 W dusting settings among endourologist familiar with TFL were evaluated. We directly compared short pulse (SP) vs long pulse (LP) mode using various combinations of pulse energy (E p ) and pulse frequency (F). Thereafter, we tested the 10 and 20 W settings and compared them among each other to elucidate the most efficient settings at each power. Treatments were performed under the same total laser energy delivered to the stone at four different standoff distances (SDs) with a clinically relevant scanning speed of either 1 or 2 mm/sec. Ablation volumes were quantified by optical coherence tomography to assess stone dusting efficiency. Fragment size after ablation at different pulse energies was evaluated by sieving and evaluating under a microscope after treatment. Results: Overall, SP provided greater ablation volume when compared with LP. Our dusting efficiency model demonstrated that the maximum stone ablation was achieved at the combination of high energy/low frequency settings ( p &lt; 0.005) and at a SD of 0.2 mm. At all tested pulse energies, no stone phantoms were broken into fragments &gt;1 mm. Conclusions: During stone dusting with TFL, SP offers superior ablation to LP settings. Optimal dusting at clinically relevant scanning speeds of 1 and 2 mm/sec occurs at high energy/low frequency settings. Thulium lithotripsy with high E p does not result in increased fragment size.

You have accessJournal of UrologyCME1 Apr 2023PD45-06 DUSTING EFFICIENCY FOR THULIUM FIBER LASER: WHEN IT COMES TO FREQUENCY, LESS IS MORE Francois Soto Palou, Robert Medairos, Junqin Chen, Jodi Antonelli, Michael Lipkin, Glenn Preminger, and Pei Zhong Francois Soto PalouFrancois Soto Palou More articles by this author , Robert MedairosRobert Medairos More articles by this author , Junqin ChenJunqin Chen More articles by this author , Jodi AntonelliJodi Antonelli More articles by this author , Michael LipkinMichael Lipkin More articles by this author , Glenn PremingerGlenn Preminger More articles by this author , and Pei ZhongPei Zhong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003358.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Data from Holmium laser studies has taught us that optimal dusting generally require low energy and high frequency settings. In assessing thulium fiber laser (TFL) technology urologists have often relied on “traditional” dusting settings obtained from Holmium laser trials and experiments. However, these two platforms are fundamentally different in their pulse profile and energy (Ep) delivery. Clinical TFL platforms have an energy range of 0.025J-6J and a frequency (F) range of 1Hz-2400Hz. With the seemingly endless combination of settings and lack of scientific evidence to support one over the other, we aim to provide guidance to the practicing urologists and assess the efficiency of the TFL platform in an automated in vitro “dusting model”. METHODS: All tests were conducted using an IPG Photonics TLR-50W TFL system and a 200μm fiber on “soft” (5:2) Begostone phantoms. We selected the most popular dusting settings (Figure 1) among endourologists familiar with TFL1 and tested each combination of Ep and F settings at four different standoff distances (SD) (0.2mm, 0.5mm 1mm, 2mm) and at clinically significant scanning speeds of 1mm/sec or 2mm/sec, under the same total laser energy delivered to the stone (i.e., 40 J). All pulses were adjusted to maximum peak power and the corresponding pulse duration. The laser fiber was scanned in a 15mm straight line with a 3D positioning system across a polished and submerged Begostone surface. Ablation volumes were quantified by optical coherence tomography (OCT). RESULTS: The maximum stone ablation was achieved at the combination of high energy and low frequency settings (p<0.005). Overall, the settings that produced the greatest ablation volume were 1J/10Hz (2.51mm3) and 1J/20Hz (2.55mm3). For the rectangular pulse profile typically used in TFL, as SD increased ablation volume decreased. CONCLUSIONS: The most efficient dusting settings for dusting using the current TFL occur at high energy, low frequency, and at a short SD of 0.2mm. Further studies are warranted to compare dusting efficiency produced by these settings using human kidney stones. Reference: 1. Sierra A, Corrales M, Piñero A, Traxer O. Thulium fiber laser pre-settings during ureterorenoscopy: Twitter's experts' recommendations. World J Urol. 2022;40(6):1529-1535. doi:10.1007/s00345-022-03966-9 Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1164 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francois Soto Palou More articles by this author Robert Medairos More articles by this author Junqin Chen More articles by this author Jodi Antonelli More articles by this author Michael Lipkin More articles by this author Glenn Preminger More articles by this author Pei Zhong More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023MP23-08 SHORT PULSE VS. LONG PULSE ABLATION WITH THE THULIUM FIBER LASER, AN IN VITRO STUDY Francois Soto Palou, Robert Medairos, Junqin Chen, Jodi Antonelli, Michael Lipkin, Glenn Preminger, and Pei Zhong Francois Soto PalouFrancois Soto Palou More articles by this author , Robert MedairosRobert Medairos More articles by this author , Junqin ChenJunqin Chen More articles by this author , Jodi AntonelliJodi Antonelli More articles by this author , Michael LipkinMichael Lipkin More articles by this author , Glenn PremingerGlenn Preminger More articles by this author , and Pei ZhongPei Zhong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003248.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The thulium fiber laser (TFL) is becoming of interest to Urologists due to its unique properties. The TFL pulse profile consists of rectangular pulses, designed for enhancing photothermal ablation. Energy for each pulse may be modified by altering pulse duration or peak power. Our aim for this study is to compare short pulse (SP) versus long pulse (LP) for common 10 W dusting settings using the TFL platform. METHODS: All tests were conducted using an IPG Photonics TLR-50 W TFL system and a 200 μm fiber on “soft” (5:2) Begostone phantoms. The most popular 10 W dusting settings (Figure 1) among endourologists familiar with TFL were evaluated.[1] Four different standoff distances (0.2 mm, 0.5 mm 1 mm, 2 mm), and a clinically significant scanning speed of 1 mm/sec was used. The pulse profiles were altered for each energy setting to produce a short pulse (SP) and a long pulse (LP) design. The laser fiber was scanned in a 15 mm straight line with a 3D positioning system across a polished and submerged Begostone surface. Ablation volumes were quantified by optical coherence tomography (OCT). RESULTS: Overall, SP provided greater ablation volume when compared to LP. The greatest difference observed between SP and LP was at 1J/10 Hz and SD of 0.2 mm (2.51 mm3 vs. 0.35 mm3) and this difference was statistically significant (p<0.005). Out of the 20 performed trials there were only two instances in which LP outperformed SP in terms of ablation volume: 0.4J/25 Hz at SD of 2 mm (0 mm3 vs. 0.15 mm3) and 0.2J/50 Hz at SD of 0.2 mm (0.79 mm3 vs 0.81 mm3). In the latter case, however, the difference was not found to be statistically significant (p=0.7). CONCLUSIONS: TFL short pulse profile offers superior trough ablation volumes than long pulse during dusting under clinically relevant scanning speed of 1 mm/s with a time average power of 10 W. [1] Sierra A, Corrales M, Piñero A, Traxer O. Thulium fiber laser pre-settings during ureterorenoscopy: Twitter's experts' recommendations. World J Urol. 2022;40(6):1529-1535. doi:10.1007/s00345-022-03966-9. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e308 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francois Soto Palou More articles by this author Robert Medairos More articles by this author Junqin Chen More articles by this author Jodi Antonelli More articles by this author Michael Lipkin More articles by this author Glenn Preminger More articles by this author Pei Zhong More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023MP35-12 ASSESSMENT OF DUST QUALITY WHILE ABLATING WITH THULIUM FIBER LASER, AN IN VITRO STUDY Francois Soto Palou, Robert Medairos, Junqin Chen, Jodi Antonelli, Michael Lipkin, Glenn Preminger, and Pei Zhong Francois Soto PalouFrancois Soto Palou More articles by this author , Robert MedairosRobert Medairos More articles by this author , Junqin ChenJunqin Chen More articles by this author , Jodi AntonelliJodi Antonelli More articles by this author , Michael LipkinMichael Lipkin More articles by this author , Glenn PremingerGlenn Preminger More articles by this author , and Pei ZhongPei Zhong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003269.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous benchtop studies have shown that optimal stone ablation with the thulium fiber laser (TFL) is achieved with short pulse and maximum peak power. Furthermore, in vitro TFL studies have also demonstrated that at equivalent power, the combination of higher energy and lower frequency offers the most efficient dusting settings. Holmium based benchtop studies have shown that low pulse energy produces small fragments while high pulse energy produces larger fragments.1 No such studies have been performed with the TFL platform, and thus with this study we aim to assess the quality and size of fragments produced at different pulse energies. METHODS: All tests were conducted using an IPG Photonics TLR-50W TFL system and a 200 μm fiber on “soft” (5:2) Begostone 6 mm×6 mm (H×D) phantoms. We tested six different pulse energies (0.05 J, 0.1 J, 0.2 J, 0.4 J, 0.5 J, and 1 J) at varying frequencies to produce either 10 W or 20 W of power. Our previous benchtop studies have shown that short pulse provides superior ablation, so all pulse profiles were adjusted to maximum peak power and short pulse. The laser fiber was advanced beyond the distal end of a flexible ureteroscope (Dornier AXISTM, 3.6 F working channel) and the stone phantoms were treated in a test tube filled with water and immersed in a water bath at room temperature (Figure 1). Continuous dusting was performed for 1 minute with the 10 W settings, and 30 seconds with the 20 W settings. Each pulse energy was tested three times with three different stone phantoms. Resultant fragments were sieved, dried for 24 hours and examined under the microscope. RESULTS: At all tested pulse energies, no stone phantoms were broken into large fragments. All stone materials were pulverized into small dust. When examined under the microscope, individual dust particles were smaller than 20 μm for all the tested settings (Figure 1). Exact measurements were not obtained and deemed not clinically relevant. CONCLUSIONS: Unlike Holmium lithotripsy where higher pulse energy results in larger fragments, in Thulium lithotripsy higher pulse energy did not result in increased fragment size. Reference: 1. Sea J, Jonat LM, Chew BH, Qiu J, Wang B, Hoopman J, Milner T, Teichman JM. Optimal power settings for Holmium:YAG lithotripsy. J Urol. 2012 Mar;187(3):914-9. doi: 10.1016/j.juro.2011.10.147. Epub 2012 Jan 20. PMID: 22264464. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e474 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francois Soto Palou More articles by this author Robert Medairos More articles by this author Junqin Chen More articles by this author Jodi Antonelli More articles by this author Michael Lipkin More articles by this author Glenn Preminger More articles by this author Pei Zhong More articles by this author Expand All Advertisement PDF downloadLoading ...

Background and objective: All clinical shock wave lithotripters produce an axisymmetric acoustic field without accounting for the anatomic features of the kidney or respiratory motion of the patient. This work presents a steerable and adjustable focusing electrohydraulic (SAFE) shock wave generator design with variable beam size and shape. Materials and Methods: 90 electrohydraulic transducers are mounted concentrically on a spherical basin with adjustable connection to individual transducers. Each transducer consists of 45 3D-printed titanium microelectrodes embedded in epoxy with a tip diameter of 0.3 mm. All the transducers are arranged in 5 concentric rings and sub-divided into 6 sectors. Results: By changing the connections of individual transducers, the focused pressure field produced by the transducer array can be either axisymmetric with a -6 dB focal width of 14.8 mm in diameter, or non-axisymmetric with a long axis of 22.7 mm and a short axis of 15.1 mm. The elongated beam produces a peak positive pressure of 33.7±4.1 MPa and comminution efficiency of 42.2±3.5%, compared to 36.2±0.7 MPa and 28.6±6.1% for axisymmetric beam after 150 pulses at 20 kV. Conclusions: We have demonstrated that the SAFE shock wave generator can produce an elongated non-axisymmetric pressure field with higher stone comminution efficiency. The SAFE shock wave generator may provide a flexible and versatile design to achieve accurate, stable, and safe lithotripsy for kidney stone treatment.

Recent studies indicate that cavitation may play a vital role in laser lithotripsy. However, the underlying bubble dynamics and associated damage mechanisms are largely unknown. In this study, we use ultra-high-speed shadowgraph imaging, hydrophone measurements, three-dimensional passive cavitation mapping (3D-PCM), and phantom test to investigate the transient dynamics of vapor bubbles induced by a holmium:yttrium aluminum garnet laser and their correlation with solid damage. We vary the standoff distance (SD) between the fiber tip and solid boundary under parallel fiber alignment and observe several distinctive features in bubble dynamics. First, long pulsed laser irradiation and solid boundary interaction create an elongated “pear-shaped” bubble that collapses asymmetrically and forms multiple jets in sequence. Second, unlike nanosecond laser-induced cavitation bubbles, jet impact on solid boundary generates negligible pressure transients and causes no direct damage. A non-circular toroidal bubble forms, particularly following the primary and secondary bubble collapses at SD = 1.0 and 3.0 mm, respectively. We observe three intensified bubble collapses with strong shock wave emissions: the intensified bubble collapse by shock wave, the ensuing reflected shock wave from the solid boundary, and self-intensified collapse of an inverted “triangle-shaped” or “horseshoe-shaped” bubble. Third, high-speed shadowgraph imaging and 3D-PCM confirm that the shock origins from the distinctive bubble collapse form either two discrete spots or a “smiling-face” shape. The spatial collapse pattern is consistent with the similar BegoStone surface damage, suggesting that the shockwave emissions during the intensified asymmetric collapse of the pear-shaped bubble are decisive for the solid damage.

Passive cavitation mapping (PCM), which generates images using bubble acoustic emission signals, has been increasingly used for monitoring and guiding focused ultrasound surgery. This study investigates a transient angular spectrum (AS) approach for PCM. The working principle of this approach is to backpropagate the received signal to the domain of interest and reconstruct the spatial–temporal wavefield encoded with the bubble location and collapse time. The transient AS approach is validated using an in silico model, water bath, and in vivo experiments. It is found that the transient AS approach yields similar results to delay and sum, but is considerably faster. The results obtained by this study suggest that the transient AS approach is promising for fast and accurate PCM.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. Early identification of patients who may advance to critical stages is crucial. This investigation aimed to establish models to predict SFTS before it reaches the critical illness stage. METHODS: Between January 2016 and September 2022, 278 cases have been included in this study. There were 87 demographic and systemic chosen variables. For selecting the predictive variables from the cohort, the LASSO was utilized, and for identifying independent predictors, multivariate logistic regression was performed. Based on these factors, a nomogram was established for critical illness. Concordance index values, decision curve analysis and the area under the curve (AUC) were also examined. RESULTS: Multivariate logistic regression demonstrated the most important differentiating factors as;> 65 years old (P < 0.001, OR 3.388, 95 % CI 1.767-6.696), elevated serum PT (P = 0.011, OR 6.641, 95 % CI 1.584-31.934), elevated serum TT (P = 0.005, OR 3.384, 95 % CI 1.503-8.491), and elevated serum bicarbonate (P = 0.014, OR 0.242, 95 % CI 0.070-0.707). The C-index of the nomogram was 0.812 (95 % CI: 0.754-0.869), representing good discrimination. The model also showed excellent calibration. The AUC of the nomogram established based on four factors, as mentioned earlier, was 0.806. Furthermore, the model had the excellent net benefit, as revealed by the decision curve analysis. CONCLUSION: An accurate risk score system built on manifestations noted in patients with SFTS upon admission to hospital, might be advantageous in managing SFTS.