In Vivo Cavitation-based Aberration Correction of Histotripsy in Porcine Liver.

Histotripsy is a non-invasive ablation technique that focuses ultrasound pulses into the body to destroy tissues via cavitation. Heterogeneous acoustic paths through tissue introduce phase errors that distort and weaken the focus, requiring additional power output from the histotripsy transducer to perform therapy. This effect, termed phase aberration, limits the safety and efficacy of histotripsy ablation. It has been shown in vitro that the phase errors from aberration can be corrected by receiving the acoustic signals emitted by cavitation. For transabdominal histotripsy in vivo, however, cavitation-based aberration correction is complicated by acoustic signal clutter and respiratory motion. This study develops a method that enables robust, effective cavitation-based aberration correction in vivo and evaluates its efficacy in the swine liver. The method begins with a high-speed pulsing procedure to minimize the effects of respiratory motion. Then, an optimal phase correction is obtained in the presence of acoustic clutter by filtering with the singular value decomposition. This aberration correction method reduced the power required to generate cavitation in the liver by 26% on average (range: 0% to 52%) and required ~2 s for signal acquisition and processing per focus location. These results suggest that the cavitation-based method could enable fast and effective aberration correction for transabdominal histotripsy.

Neuronavigation-Guided Transcranial Histotripsy (NaviTH) System.

OBJECTIVE: The goal of the work described here was to develop the first neuronavigation-guided transcranial histotripsy (NaviTH) system and associated workflow for transcranial ablation. METHODS: The NaviTH system consists of a 360-element, 700 kHz transmitter-receiver-capable transcranial histotripsy array, a clinical neuronavigation system and associated equipment for patient-to-array co-registration and therapy planning and targeting software systems. A workflow for NaviTH treatments, including pre-treatment aberration correction, was developed. Targeting errors stemming from target registration errors (TREs) during the patient-to-array co-registration process, as well as focal shifts caused by skull-induced aberrations, were investigated and characterized. The NaviTH system was used in treatments of two <96 h post-mortem human cadavers and in experiments in two excised human skullcaps. RESULTS: The NaviTH was successfully used to create ablations in the cadaver brains as confirmed in post-treatment magnetic resonance imaging A total of three ablations were created in the cadaver brains, and targeting errors of 9, 3.4 and 4.4 mm were observed in corpus callosum, septum and thalamus targets, respectively. Errors were found to be caused primarily by TREs resulting from transducer tracking instrument design flaws and imperfections in the treatment workflow. Transducer tracking instrument design and workflow improvements reduced TREs to <2 mm, and skull-induced focal shifts, following pre-treatment aberration correction, were 0.3 mm. Total targeting errors of the NaviTH system following the noted improvements were 2.5 mm. CONCLUSIONS: The feasibility of using the first NaviTH system in a human cadaver model has been determined. Although accuracy still needs to be improved, the proposed system has the potential to allow for transcranial histotripsy therapies without requiring active magnetic resonance treatment guidance.

Nanoparticle-Mediated Histotripsy Using Dual-Frequency Pulsing Methods.

OBJECTIVE: Nanoparticle-mediated histotripsy (NMH) is a novel ablation method that combines nanoparticles as artificial cavitation nuclei with focused ultrasound pulsing to achieve targeted, non-invasive, and cell-selective tumor ablation. The study described here examined the effect of dual-frequency histotripsy pulsing on the cavitation threshold, bubble cloud characteristics, and ablative efficiency in NMH. High-speed optical imaging was used to analyze bubble cloud characteristics and to measure ablation efficiency for NMH inside agarose tissue phantoms containing perfluorohexane-filled nanocone clusters, which were previously developed to reduce the histotripsy cavitation threshold for NMH. METHODS: Dual-frequency histotripsy pulsing was applied at a 1:1 pressure ratio using a modular 500 kHz and 3 MHz dual-frequency array transducer. Optical imaging results revealed predictable, well-defined bubble clouds generated for all tested cases with similar reductions in the cavitation thresholds observed for single-frequency and dual-frequency pulsing. RESULTS: Dual-frequency pulsing was seen to nucleate small, dense clouds in agarose phantoms, intermediate in size of their component frequencies but closer in area to that of the higher component frequency. Red blood cell experiments revealed complete ablations were generated by dual-frequency NMH in all phantoms in <1500 pulses. This result was a significant increase in ablation efficiency compared with the ∼4000 pulses required in prior single-frequency NMH studies. CONCLUSION: Overall, this study indicates the potential for using dual-frequency histotripsy methods to increase the ablation efficacy of NMH.

Assessing renal tissue temperature changes and perfusion effects during laser activation in an in vivo porcine model.

INTRODUCTION: High fluid temperatures have been seen in both in vitro and in vivo studies with laser lithotripsy, yet the thermal distribution within the renal parenchyma has not been well characterized. Additionally, the heat-sink effect of vascular perfusion remains uncertain. Our objectives were twofold: first, to measure renal tissue temperatures in response to laser activation in a calyx, and second, to assess the effect of vascular perfusion on renal tissue temperatures. METHODS: Ureteroscopy was performed in three porcine subjects with a prototype ureteroscope containing a temperature sensor at its tip. A needle with four thermocouples was introduced percutaneously into a kidney with ultrasound guidance to allow temperature measurement in the renal medulla and cortex. Three trials of laser activation (40W) for 60 s were conducted with an irrigation rate of 8 ml/min at room temperature in each subject. After euthanasia, three trials were repeated without vascular perfusion in each subject. RESULTS: Substantial temperature elevation was observed in the renal medulla with thermal dose in two of nine trials exceeding threshold for tissue injury. The temperature decay time (t½) of the non-perfused trials was longer than in the perfused trials. The ratio of t½ between them was greater in the cortex than the medulla. CONCLUSION: High-power laser settings (40W) can induce potentially injurious temperatures in the in vivo porcine kidney, particularly in the medullary region adjacent to the collecting system. Additionally, the influence of vascular perfusion in mitigating thermal risk in this susceptible area appears to be limited.

An Ultrasound Array of Emitter-Receiver Stacks for Microbubble-Based Therapy.

Most therapeutic ultrasound devices place emitters and receivers in separate locations, so that the long therapeutic pulses (>1 ms) can be emitted while receivers monitor the procedure. However, with such placement, emitters and receivers are competing for the same space, producing a trade-off between emission efficiency and reception sensitivity. Taking advantage of recent studies demonstrating that short-pulse ultrasound can be used therapeutically, we aimed to develop a device that overcomes such trade-offs. The array was composed of emitter-receiver stacks, which enabled both emission and reception from the same location. Each element was made of a lead zirconate titanate (PZT)-polyvinylidene fluoride (PVDF) stack. The PZT (frequency: 500 kHz, diameter: 16 mm) was used for emission and the PVDF (thickness: 28 µm, diameter: 16 mm) for broadband reception. 32 elements were assembled in a 3D-printed dome-shaped frame (focal length: 150 mm; [Formula: see text]-number: 1) and was tested in free-field and through an ex-vivo human skull. In free-field, the array had a 4.5 × 4.5 × 32 mm focus and produced a peak-negative pressure (PNP) of 2.12 MPa at its geometric center. The electronic steering range was ±15 mm laterally and larger than ±15 mm axially. Through the skull, the array produced a PNP of 0.63 MPa. The PVDF elements were able to localize broadband microbubble emissions across the skull. We built the first multi-element array for short-pulse and microbubble-based therapeutic applications. Stacked arrays overcome traditional trade-offs between the transmission and reception quality and have the potential to create a step change in treatment safety and efficacy.

Multichannel resonant acoustic rheometry system for quantification of coagulation of multiple human plasma samples.

Resonant Acoustic Rheometry (RAR), a newly developed ultrasound-based technique for non-contact characterization of soft viscoelastic materials, has shown promise for quantitative viscoelastic assessment of temporally changing soft biomaterials in real time, and may be used to monitor blood coagulation process. Here, we report the development of a novel, multichannel RAR (mRAR) system for simultaneous measurements of multiple temporally evolving samples and demonstration of its use for monitoring the coagulation of multiple small-volume plasma samples. The mRAR system was constructed using an array of 4 custom-designed ultrasound transducers at 5.0 MHz and a novel electronic driving system that controlled the generation of synchronized ultrasound pulses for real time assessment of multiple samples simultaneously. As a proof-of-concept of the operation of the mRAR system, we performed tests using pooled normal human plasma samples and anti-coagulated plasma samples from patients treated with warfarin with a range of International Normalized Ratio (INR) values as well-characterized samples with different coagulation kinetics. Our results show that simultaneous tracking of dynamic changes in 4 plasma samples triggered by either kaolin or tissue factor was achieved for the entire duration of coagulation. The mRAR system captured distinct changes in the samples and identified parameters including the clotting start time and parameters associated with the stiffness of the final clots that were consistent with INR levels. Data from this study demonstrate the feasibility of the mRAR system for efficient characterization of the kinetic coagulation processes of multiple plasma samples.

Bubble cloud characteristics and ablation efficiency in dual-frequency intrinsic threshold histotripsy.

Histotripsy is a non-thermal focused ultrasound ablation method that destroys tissue through the generation and activity of acoustic cavitation bubble clouds. Intrinsic threshold histotripsy uses single-cycle pulses to generate bubble clouds when the dominant negative pressure phase exceeds an intrinsic threshold of ∼25-30 MPa. The ablation efficiency is dependent upon the size and density of bubbles within the bubble cloud. This work investigates the effects of dual-frequency pulsing schemes on the bubble cloud behavior and ablation efficiency in intrinsic threshold histotripsy. A modular 500 kHz:3 MHz histotripsy transducer treated agarose phantoms using dual-frequency histotripsy pulses with a 1:1 pressure ratio from 500 kHz and 3 MHz frequency elements and varying arrival times for the 3 MHz pulse relative to the arrival of the 500 kHz pulse (-100 ns, 0 ns, and +100 ns). High-speed optical imaging captured cavitation effects to characterize bubble cloud and individual bubble dynamics. The effects of dual-frequency pulsing on lesion formation and ablation efficiency were also investigated in red blood cell (RBC) phantoms. Results showed that the single bubble and bubble cloud size for dual-frequency cases were intermediate to published results for the component single-frequencies of 500 kHz and 3 MHz. Additionally, bubble cloud size and dynamics were shown to be altered by the arrival time of the 3 MHz pulse with respect to the 500 kHz pulse, with more uniform cloud expansion and collapse observed for early (-100 ns) arrival. Finally, RBC phantom experiments showed that dual-frequency exposures were capable of generating precise lesions with smaller areas and higher ablation efficiencies than previously published results for 500 kHz or 3 MHz. Overall, results demonstrate dual-frequency histotripsy's ability to modulate bubble cloud size and dynamics can be leveraged to produce precise lesions at higher ablation efficiencies than previously observed for single-frequency pulsing.

Aberration correction in abdominal histotripsy.

In transabdominal histotripsy, ultrasound pulses are focused on the body to noninvasively destroy soft tissues via cavitation. However, the ability to focus is limited by phase aberration, or decorrelation of the ultrasound pulses due to spatial variation in the speed of sound throughout heterogeneous tissue. Phase aberration shifts, broadens, and weakens the focus, thereby reducing the safety and efficacy of histotripsy therapy. This paper reviews and discusses aberration effects in histotripsy and in related therapeutic ultrasound techniques (e.g., high intensity focused ultrasound), with an emphasis on aberration by soft tissues. Methods for aberration correction are reviewed and can be classified into two groups: model-based methods, which use segmented images of the tissue as input to an acoustic propagation model to predict and compensate phase differences, and signal-based methods, which use a receive-capable therapy array to detect phase differences by sensing acoustic signals backpropagating from the focus. The relative advantages and disadvantages of both groups of methods are discussed. Importantly, model-based methods can correct focal shift, while signal-based methods can restore substantial focal pressure, suggesting that both methods should be combined in a 2-step approach. Aberration correction will be critical to improving histotripsy treatments and expanding the histotripsy treatment envelope to enable non-invasive, non-thermal histotripsy therapy for more patients.

Change in renal blood flow in response to intrarenal pressure alterations induced by ureteroscopy in an in-vivo porcine model.

INTRODUCTION: High irrigation rates are commonly used during ureteroscopy and can increase intrarenal pressure (IRP) substantially. Concerns have been raised that elevated IRP may diminish renal blood flow (RBF) and perfusion of the kidney. Our objective was to investigate the real-time changes in RBF while increasing IRP during Ureteroscopy (URS) in an in-vivo porcine model. METHODS: Four renal units in two porcine subjects were used in this study, three experimental units and one control. For the experimental units, RBF was measured by placing an ultrasonic flow cuff around the renal artery, while performing ureteroscopy in the same kidney using a prototype ureteroscope with a pressure sensor at its tip. Irrigation was cycled between two rates to achieve targeted IRPs of 30 mmHg and 100 mmHg. A control data set was obtained by placing the ultrasonic flow cuff on the contralateral renal artery while performing ipsilateral URS. RESULTS: At high IRP, RBF was reduced in all three experimental trials by 10-20% but not in the control trial. The percentage change in RBF due to alteration in IRP was internally consistent in each porcine renal unit and independent of slower systemic variation in RBF encountered in both the experimental and control units. CONCLUSION: RBF decreased 10-20% when IRP was increased from 30 to 100 mmHg during ureteroscopy in an in-vivo porcine model. While this reduction in RBF is unlikely to have an appreciable effect on tissue oxygenation, it may impact heat-sink capacity in vulnerable regions of the kidney.

Multichannel Resonant Acoustic Rheometry System for Rapid and Efficient Quantification of Human Plasma Coagulation.

Resonant Acoustic Rheometry (RAR), a newly developed ultrasound-based technique for non-contact characterization of soft viscoelastic materials, has shown promise for quantitative assessment of plasma coagulation by monitoring the entire dynamic process in real time. Here, we report the development of a multichannel RAR (mRAR) system for simultaneous monitoring of the coagulation of multiple small-volume plasma samples, a capability that is critical to efficiently provide improved assessment of coagulation. The mRAR system was constructed using an array of 4 custom-designed ultrasound transducers at 5.0 MHz and an electronic driving system that controlled the generation of synchronized ultrasound pulses for real time monitoring of multiple samples simultaneously. The mRAR system was tested using Coumadin-treated plasma samples with a range of International Normalized Ratio (INR) values, as well as normal pooled plasma samples. Tracking of dynamic changes in clotting of plasma samples triggered by either kaolin or tissue factor was performed for the entire duration of coagulation. The mRAR system captured distinct changes in the samples and identified parameters including clotting time, clotting speed, and the mechanical properties of the clots that were consistent with Coumadin dose and INR levels Data from this study demonstrate the feasibility of the mRAR system for the rapid, efficient, and accurate characterization of plasma coagulation.

Effect of outflow resistance on intrarenal pressure at different irrigation rates during ureteroscopy: in vivo evaluation.

To maintain visualization and control temperature elevation during ureteroscopy, higher irrigation rates are necessary, but this can increase intrarenal pressure (IRP) and lead to adverse effects like sepsis. The IRP is also dependent on outflow resistance but this has not been quantitatively evaluated in a biological system. In this study, we sought to characterize the IRP as a function of irrigation rate in an in vivo porcine model at different outflow resistances. Ureteroscopy was performed in a porcine model with a 9.5 Fr prototype ureteroscope containing a pressure sensor. A modified ureteral access sheath (UAS) (11/13 Fr, 36 cm) was configured to adjust outflow resistance. IRP-irrigation rate curves were generated at four different outlet resistances representing different outflow scenarios. At lower irrigation rates, the pressure change in response to increased irrigation was gradual and non-linear, likely reflecting a "compliant" phase of the renal collecting system. Once IRP reached the range of 35-50 cm H2O, the pressure increased in a linear fashion with irrigation rate, suggesting that the distensibility of the collecting system had become saturated. The relationship between IRP and irrigation rate becomes linear during in vivo porcine studies once the initial compliance of the system is saturated. IRP is more sensitive to changes in irrigation rate in systems with higher outflow resistance. The modified UAS is a novel research tool which allows variance of outflow resistance to mimic different clinical scenarios. Knowledge of outflow resistance may simplify the decision to use an UAS.

Thermal Safety Boundaries for Laser Power and Irrigation Rate During Ureteroscopy: In Vivo Porcine Assessment With a Ho:YAG Laser.

OBJECTIVE: To map thermal safety boundaries during ureteroscopy (URS) with laser activation in two in vivo porcine subjects to better understand the interplay between laser power, irrigation rate, and fluid temperature in the collecting system. METHODS: URS was performed in two in vivo porcine subjects with a prototype ureteroscope containing a thermocouple at its tip. Up to 6 trials of 60 seconds laser activation were carried out at each selected power setting and irrigation rate. Thermal dose was calculated for each trial, and laser power-irrigation rate parameter pairs were categorized based on number of trials that exceeded a thermal dose of 120 equivalent minutes. RESULTS: The collecting fluid temperature was increased with greater laser power and slower irrigation rate. In the first porcine subject, 25 W of laser power could safely be applied if irrigation was at least 15 mL/min, and 48 W with at least 30 mL/min. Intermediate values followed a linear curve between these bounds. For the second subject, where the calyx appeared larger, 15 W laser power required 9 mL/min irrigation, 48 W required 24 mL/min, and intermediate points also followed a near-linear curve. CONCLUSION: This study validates previous bench research and provides a conceptual framework for selection of safe laser lithotripsy settings and irrigation rates during URS with laser lithotripsy. Additionally, it provides insight and guidance for future development of thermal mitigation strategies and devices.

Magnetic Resonance Thermometry Targeting for Magnetic Resonance-Guided Histotripsy Treatments.

OBJECTIVE: The potential of transcranial magnetic resonance (MR)-guided histotripsy for brain applications has been described in prior in vivo studies in the swine brain through an excised human skull. The safety and accuracy of transcranial MR-guided histotripsy (tcMRgHt) rely on pre-treatment targeting guidance. In the work described here, we investigated the feasibility and accuracy of using ultrasound-induced low-temperature heating and MR thermometry for histotripsy pre-treatment targeting in ex vivo bovine brain. METHODS: A 15-element, 750-kHz MRI-compatible ultrasound transducer with modified drivers that can deliver both low-temperature heating and histotripsy acoustic pulses was used to treat seven bovine brain samples. The samples were first heated to an approximately 1.6°C temperature increase at the focus, and MR thermometry was used to localize the target. Once the targeting was confirmed, a histotripsy lesion was generated at the focus and visualized on post-histotripsy MR images. DISCUSSION: The accuracy of MR thermometry targeting was evaluated with the mean/standard deviation of the difference between the locus of peak heating identified by MR thermometry and the center of mass of the post-treatment histotripsy lesion, which was 0.59/0.31 mm and 1.31/0.93 mm in the transverse and longitudinal directions, respectively. CONCLUSION: This study determined that MR thermometry could provide reliable pre-treatment targeting for transcranial MR-guided histotripsy treatment.

Quantification of outflow resistance for ureteral drainage devices used during ureteroscopy.

PURPOSE: Since renal pelvis pressure is directly related to irrigation flowrate and outflow resistance, knowledge of outflow resistance associated with commonly used drainage devices could help guide the selection of the type and size of ureteral access sheath or catheter for individual ureteroscopic cases. This study aims to quantitatively measure outflow resistance for different drainage devices utilized during ureteroscopy. METHODS: With measured irrigation flowrate and renal pelvis pressure, outflow resistance was calculated using a hydrodynamic formula. After placement of a drainage device into a silicone kidney-ureter model, a disposable ureteroscope with a 9.5-Fr outer diameter was inserted with its tip positioned at the renal pelvis. Irrigation was delivered through the ureteroscope from varying heights above the renal pelvis. Renal pelvis pressure was measured directly from the port of the kidney model using a pressure sensor (Opsens, Canada). Outflow resistance was determined by plotting flowrate versus renal pelvis pressure. All trials were performed in triplicate for each drainage device inserted. RESULTS: Flowrate was linearly dependent on renal pelvis pressure for all drainage devices tested. Outflow resistance values were 0.2, 1.1, 1.4, 3.9, and 6.5 cmH2O/[ml/min] for UAS 13/15 Fr, UAS 11/13 Fr, UAC 6 Fr, UAC 4.8 Fr, and UAC 4.0 Fr, respectively, across the range of commonly used irrigation flowrates. CONCLUSIONS: In this study, outflow resistance of different ureteral drainage devices was quantitatively measured. This knowledge can be useful when selecting which type and size of drainage device to insert to maintain safe renal pelvis pressure during ureteroscopy.

Soft Tissue Aberration Correction for Histotripsy Using Acoustic Emissions From Cavitation Cloud Nucleation and Collapse.

OBJECTIVE: Phase aberration from soft tissue limits the efficacy of histotripsy, a therapeutic ultrasound technique based on acoustic cavitation. Previous work has shown that the acoustic emissions from cavitation can serve as "point sources" for aberration correction (AC). This study compared the efficacy of soft tissue AC for histotripsy using acoustic cavitation emissions (ACE) from bubble cloud nucleation and collapse. METHODS: A 750-kHz, receive-capable histotripsy array was pulsed to generate cavitation in ex vivo porcine liver through an intervening abdominal wall. Received ACE signals were used to determine the arrival time differences to the focus and compute corrective delays. Corrections from single pulses and from the median of multiple pulses were tested. DISCUSSION: On average, ACE AC obtained 96% ± 3% of the pressure amplitude obtained by hydrophone-based correction (compared with 71% ± 5% without AC). Both nucleation- and collapse-based corrections obtained >96% of the hydrophone-corrected pressure when using medians of ≥10 pulses. When using single-pulse corrections, nucleation obtained a range of 49%-99% of the hydrophone-corrected pressure, while collapse obtained 95%-99%. CONCLUSION: The results suggest that (i) ACE AC can recover nearly all pressure amplitude lost owing to soft tissue aberration and that (ii) the collapse signal permits robust AC using a small number of pulses.

An X-Ray C-Arm Guided Automatic Targeting System for Histotripsy.

OBJECTIVE: Histotripsy is an emerging noninvasive, nonionizing and nonthermal focal cancer therapy that is highly precise and can create a treatment zone of virtually any size and shape. Current histotripsy systems rely on ultrasound imaging to target lesions. However, deep or isoechoic targets obstructed by bowel gas or bone can often not be treated safely using ultrasound imaging alone. This work presents an alternative x-ray C-arm based targeting approach and a fully automated robotic targeting system. METHODS: The approach uses conventional cone beam CT (CBCT) images to localize the target lesion and 2D fluoroscopy to determine the 3D position and orientation of the histotripsy transducer relative to the C-arm. The proposed pose estimation uses a digital model and deep learning-based feature segmentation to estimate the transducer focal point relative to the CBCT coordinate system. Additionally, the integrated robotic arm was calibrated to the C-arm by estimating the transducer pose for four preprogrammed transducer orientations and positions. The calibrated system can then automatically position the transducer such that the focal point aligns with any target selected in a CBCT image. RESULTS: The accuracy of the proposed targeting approach was evaluated in phantom studies, where the selected target location was compared to the center of the spherical ablation zones in post-treatment CBCTs. The mean and standard deviation of the Euclidean distance was 1.4 ±0.5 mm. The mean absolute error of the predicted treatment radius was 0.5 ±0.5 mm. CONCLUSION: CBCT-based histotripsy targeting enables accurate and fully automated treatment without ultrasound guidance. SIGNIFICANCE: The proposed approach could considerably decrease operator dependency and enable treatment of tumors not visible under ultrasound.

Development of an automated laser drilling algorithm to compare stone ablation patterns from different laser pulse modes.

PURPOSE: To develop a novel automated three-dimensional (3D) laser drilling algorithm to further investigate laser-stone interaction with different laser pulse modes. Comparison of post-ablative lattice architecture combined with mass of stone ablated can provide a more complete understanding of differences between pulse mode. METHODS: A 3D positioner (securing laser fiber) was programmed to create a 5 × 5 grid of drill holes spaced 1 mm apart on 15:5 cylindrical BegoStones. Beginning 0.5 mm above the stone surface, the laser fiber was activated and advanced 2 mm toward and into the stone for all 25 points. Four trials for each pulse mode [short pulse (SP), long pulse (LP), Moses Contact (MC), Moses Distance (MD)] were completed. Outcome measures were assessment of lattice preservation and mass of ablated stone. RESULTS: MC exhibited the greatest lattice preservation and least stone mass ablated (50.5 ± 2.2 mg). SP (69.4 ± 4.3 mg) and MD (70.0 ± 2.6 mg) had the greatest lattice destruction and stone mass ablated. The differences in stone ablated between MC and MD (p = 0.00003), MC and SP (p = 0.0002), and LP and MD (p = 0.004) were statistically significant. CONCLUSIONS: Consistent quantitative and qualitative differences between pulse modes were observed with a novel automated 3D laser drilling algorithm applied to BegoStone. The laser drilling algorithm developed here can be used to further enhance mechanistic understanding of laser-stone interactions and facilitate selection of appropriate laser pulse modes to balance precision and efficiency across the range of laser lithotripsy techniques.

Determination of Irrigation Flowrate During Flexible Ureteroscopy: Methods for Calculation Using Renal Pelvis Pressure.

Background: Proper control of irrigation flowrate during ureteroscopy is important to manage thermal and pressure risks. This task is challenging because flowrate is not directly measured by commercially available ureteroscopic or fluid management systems. However, flowrate can be calculated using a hydrodynamic relationship based on measurable values during ureteroscopy. Objectives of this in vitro study were to (1) calculate inflow resistance for different working channel conditions and then using these values and (2) calculate irrigation flowrate and determine its accuracy across a range of renal pelvis pressures. Materials and Methods: A 16 L container was filled with deionized water and connected by irrigation tubing to a 9.6F single-use ureteroscope. Inflow resistance was determined by plotting flowrate (mass of fluid collected from ureteroscope tip in 60 seconds) vs irrigation pressure (range 0-200 cmH2O). Next, the tip of the ureteroscope was inserted into the renal pelvis of a silicone kidney-ureter model and renal pelvis pressure was measured. In conjunction with the previously determined inflow resistance and known irrigation pressure values, flowrate was calculated and compared with experimentally measured values. All trials were performed in triplicate for working channel conditions: empty, 200 µm laser fiber, 365 µm laser fiber, and 1.9F stone basket. Results: Flowrate was linearly dependent on irrigation pressure for each working channel condition. Inflow resistance was determined to be 5.0 cmH2O/(mL/min) with the 200 µm laser fiber in the working channel and calculated flowrates were within 1 mL/min of measured flowrates. Similar results were seen with a 365 µm laser fiber, and 1.9F basket. Conclusions: Utilizing renal pelvis pressure measurements, flowrate was accurately calculated across a range of working channel conditions and irrigation pressures. Incorporation of this methodology into future ureteroscopic systems that measure intrarenal pressure could provide a real-time readout of flowrate for the urologist and thereby enhance safety and efficiency of laser lithotripsy.

Characterization of Fluid Dynamics and Temperature Profiles During Ureteroscopy with Laser Activation in a Model Ureter.

Introduction: Ureteral thermal injury has been reported in patients following ureteroscopy with laser lithotripsy due to overheating of fluid within the ureter. Proper understanding of this risk necessitates knowing the volume of fluid available to absorb laser energy. This can be approximated as the volume of fluid that mixes during laser activation, since energy transfer through fluid is dominated by convection. Objectives of this study were to determine the volume of fluid that mixes during laser activation at different irrigation rates and to characterize the temporal/spatial temperature distribution in a model ureter. Methods: The model ureter consisted of a plastic tube-160 mm length and 5.3 mm inner diameter. Irrigation was first applied with clear, then dyed, deionized water at rates from 8 to 40 mL/min. The laser was activated at 20 W (0.5 J/40 Hz). The distances the dyed fluid propagated were measured and volumes calculated. Temperatures were recorded from six thermocouples-five embedded within the tube and one affixed to the ureteroscope. Thermal dose was calculated using the Dewey and Sapareto methodology. Results: The volume of total fluid mixing in the model ureter was ≤1.26 ± 0.10 cm3, consistent with a sharp temperature increase after laser activation from -5 to 25 mm from the ureteroscope tip. With irrigation rates ≤12 mL/min, calculated thermal dose within the model ureter exceeded the threshold of tissue injury and extended greater distances along the ureter with lower irrigation rates. Conclusion: The volume of total fluid mixing within the model ureter was found to be small thus conferring a greater risk of ureteral thermal injury. A thermocouple positioned near the tip of the ureteroscope reasonably approximates temperature in front of the ureteroscope. Until temperature sensors are incorporated into ureteroscopic systems, laser power settings should be carefully selected to minimize risk of ureteral thermal injury.

Laser Heating of Fluid With and Without Stone Ablation: In Vitro Assessment.

Introduction: Laser lithotripsy can cause excessive heating of fluid within the collecting system and lead to tissue damage. To better understand this effect, it is important to determine the percentage of applied laser energy that is converted to heat and the percentage used for stone ablation. Our objective was to calculate the percentage of laser energy used for stone ablation based on the difference in fluid temperature measured in an in vitro model when the laser was activated without and with stone ablation. Methods: Flat BegoStone disks (15:5) were submerged in 10 mL of deionized water at the bottom of a vacuum evacuated double-walled glass Dewar. A Moses 200 D/F/L laser fiber was positioned above the surface of the stone at a distance of 3.5 mm for control (no stone ablation) or 0.5 mm for experimental (ablation) trials. The laser was activated and scanned at 3 mm/second across the stone in a preprogrammed pattern for 30 seconds at 2.5 W (0.5 J × 5 Hz) for both short-pulse (SP) and Moses distance (MD) modes. Temperature of the fluid was recorded using two thermocouples once per second. Results: Control trials produced no stone ablation, while experimental trials produced a staccato groove in the stone surface, simulating efficient lithotripsy. The mean temperature increase for SP was 1.08°C ± 0.04°C for control trials and 0.98°C ± 0.03°C for experimental trials, yielding a mean temperature difference of 0.10°C ± 0.06°C (p = 0.0005). With MD, the mean temperature increase for control trials was 1.03°C ± 0.01°C and for experimental trials 0.99°C ± 0.06°C, yielding a smaller mean temperature difference of 0.04°C ± 0.06°C (p = 0.09). Conclusions: Even under conditions of energy-efficient stone ablation, the majority of applied laser energy (91%-96%) was converted to heat.