The impact of siphoning effect on renal pelvis pressure during ureteroscopy using an in vitro kidney and ureter model.

PURPOSE: To experimentally measure renal pelvis pressure (PRP) in an ureteroscopic model when applying a simple hydrodynamic principle, the siphoning effect. METHODS: A 9.5Fr disposable ureteroscope was inserted into a silicone kidney-ureter model with its tip positioned at the renal pelvis. Irrigation was delivered through the ureteroscope at 100 cm above the renal pelvis. A Y-shaped adapter was fitted onto the model's renal pelvis port, accommodating a pressure sensor and a 4 Fr ureteral access catheter (UAC) through each limb. The drainage flowrate through the UAC tip was measured for 60 s each run. The distal tip of the UAC was placed at various heights below or above the center of the renal pelvis to create a siphoning effect. All trials were performed in triplicate for two lengths of 4Fr UACs: 100 cm and 70 cm (modified from 100 cm). RESULTS: PRP was linearly dependent on the height difference from the center of the renal pelvis to the UAC tip for both tested UAC lengths. In our experimental setting, PRP can be reduced by 10 cmH20 simply by lowering the distal tip of a 4 Fr 70 cm UAC positioned alongside the ureteroscope by 19.7 cm. When using a 4 Fr 100 cm UAC, PRP can drop 10 cmH20 by lowering the distal tip of the UAC 23.3 cm below the level of the renal pelvis. CONCLUSION: Implementing the siphoning effect for managing PRP during ureteroscopy could potentially enhance safety and effectiveness.

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.

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.

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.

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.

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.

Two-step aberration correction: application to transcranial histotripsy.

Objective: Phase aberration correction is essential in transcranial histotripsy to compensate for focal distortion caused by the heterogeneity of the intact skull bone. This paper improves the 2-step aberration correction (AC) method that has been previously presented and develops an AC workflow that fits in the clinical environment, in which the computed tomography (CT)-based analytical approach was first implemented, followed by a cavitation-based approach using the shockwaves from the acoustic cavitation emission (ACE).Approach:A 700 kHz, 360-element hemispherical transducer array capable of transmit-and-receive on all channels was used to transcranially generate histotripsy-induced cavitation and acquire ACE shockwaves. For CT-AC, two ray-tracing models were investigated: a forward ray-tracing model (transducer-to-focus) in the open-source software Kranion, and an in-house backward ray-tracing model (focus-to-transducer) accounting for refraction and the sound speed variation in skulls. Co-registration was achieved by aligning the skull CT data to the skull surface map reconstructed using the acoustic pulse-echo method. For ACE-AC, the ACE signals from the collapses of generated bubbles were aligned by cross-correlation to estimate the corresponding time delays.Main results:The performance of the 2-step method was tested with 3 excised human calvariums placed at 2 different locations in the transducer array. Results showed that the 2-step AC achieved 90 ± 7% peak focal pressure compared to the gold standard hydrophone correction. It also reduced the focal shift from 0.84 to 0.30 mm and the focal volume from 10.6 to 2.0 mm3on average compared to the no AC cases.Significance:The 2-step AC yielded better refocusing compared to either CT-AC or ACE-AC alone and can be implemented in real-time for transcranial histotripsy brain therapy.

Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model.

Histotripsy has been used for tumor ablation, through controlled, non-invasive acoustic cavitation. This is the first study to evaluate the impact of partial histotripsy ablation on immune infiltration, survival outcomes, and metastasis development, in an in vivo orthotopic, immunocompetent rat HCC model (McA-RH7777). At 7−9 days post-tumor inoculation, the tumor grew to 5−10 mm, and ~50−75% tumor volume was treated by ultrasound-guided histotripsy, by delivering 1−2 cycle histotripsy pulses at 100 Hz PRF (focal peak negative pressure P− >30 MPa), using a custom 1 MHz transducer. Complete local tumor regression was observed on MRI in 9/11 histotripsy-treated rats, with no local recurrence or metastasis up to the 12-week study end point, and only a <1 mm residual scar tissue observed on histology. In comparison, 100% of untreated control animals demonstrated local tumor progression, developed intrahepatic metastases, and were euthanized at 1−3 weeks. Survival outcomes in histotripsy-treated animals were significantly improved compared to controls (p-value < 0.0001). There was evidence of potentially epithelial-to-mesenchymal transition (EMT) in control tumor and tissue healing in histotripsy-treated tumors. At 2- and 7-days post-histotripsy, increased immune infiltration of CD11b+, CD8+ and NK cells was observed, as compared to controls, which may have contributed to the eventual regression of the untargeted tumor region in histotripsy-treated tumors.

Laser operator duty cycle effect on temperature and thermal dose: in-vitro study.

PURPOSE: High-power laser lithotripsy can elevate temperature within the urinary collecting system and increase risk of thermal injury. Temperature elevation is dependent on power settings and operator duty cycle (ODC)-the percentage of time the laser pedal is depressed. The objective of this study was to quantify temperature and thermal dose resulting from laser activation at different ODC in an in-vitro model. METHODS: Holmium laser energy (1800 J) was delivered at 30 W (0.5 J × 60 Hz) to a fluid filled glass bulb. Room temperature irrigation was applied at 8 ml/min. ODC was evaluated in 10% increments from 50-100%. Bulb fluid temperature was recorded and thermal dose calculated. Time to reach threshold of thermal injury and maximal allowable energy were also determined at each ODC. RESULTS: Upon laser activation, there was an immediate rise in fluid temperature with a "saw-tooth" oscillation superimposed on the curves for 50-90% ODC corresponding to periodic activation of the laser. Higher ODC resulted in greater maximum temperature and thermal dose, with ODC ≥ 70% exceeding threshold. Use of 50% compared to 60% ODC resulted in a tenfold increase in time required to reach threshold of thermal injury and an eightfold increase in maximal allowable energy. CONCLUSIONS: Laser activation at higher ODC produced greater fluid temperature and thermal dose. Time to threshold of thermal injury and maximal allowable energy were dramatically higher for 50% compared to 60% ODC at high-power settings. Proper management of laser ODC can enhance patient safety and optimize stone treatment.

Chilled Irrigation for Control of Temperature Elevation During Ureteroscopic Laser Lithotripsy: In Vivo Porcine Model.

Introduction: Multiple studies have shown significant heating of fluid within the urinary collecting system with high-power laser settings. Elevated fluid temperatures may cause thermal injury and tissue damage unless appropriately mitigated. A previous in vitro study demonstrated that chilled (CH) (4°C) irrigation slowed temperature rise, decreased plateau temperature, and lowered thermal dose during laser activation with high-power settings. We sought to evaluate the thermal effects of CH, room temperature (RT), and warmed (WM) irrigation during ureteroscopy with laser activation in an in vivo porcine model. Materials and Methods: Seven female Yorkshire cross pigs (45-55 kg) were anesthetized and positioned supine. Retrograde ureteroscopy was performed with a thermocouple affixed 5 mm from the distal end of the ureteroscope. In two pigs, a holmium:YAG laser was activated for 60 seconds at irrigation rates of 8, 12, and 15 mL/min with CH, RT, or WM irrigation. In five pigs, core body temperature was recorded for 1 hour with or without continuous CH irrigation at 15 mL/min. Results: At irrigation rates ≥12 mL/min, temperature curves appeared uniformly offset, WM > RT > CH irrigation. The threshold of thermal tissue injury was reached during laser activation for all irrigation temperatures at 8 mL/min. The threshold was not reached with CH irrigation at 12 or 15 mL/min, or with RT irrigation at 15 mL/min. The threshold was exceeded at all irrigation rates with WM irrigation. There was no significant change in core body temperature after delivering CH irrigation at 15 mL/min compared with no irrigation for 60 minutes. Conclusion: Irrigation with CH saline solution during ureteroscopic laser lithotripsy slows temperature rise, lowers peak temperature, and lengthens the time to thermal injury compared with irrigation with RT or WM saline solutions. Core body temperature was not significantly impacted by CH irrigation.

Transcranial Magnetic Resonance-Guided Histotripsy for Brain Surgery: Pre-clinical Investigation.

Histotripsy has been previously applied to target various cranial locations in vitro through an excised human skull. Recently, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, enabling pre-clinical investigations of tcMRgHt for brain surgery. To determine the feasibility of in vivo transcranial histotripsy, tcMRgHt treatment was delivered to eight pigs using a 700-kHz, 128-element, MR-compatible phased-array transducer inside a 3-T magnetic resonance imaging (MRI) scanner. After craniotomy to open an acoustic window to the brain, histotripsy was applied through an excised human calvarium to target the inside of the pig brain based on pre-treatment MRI and fiducial markers. MR images were acquired pre-treatment, immediately post-treatment and 2-4 h post-treatment to evaluate the acute treatment outcome. Successful histotripsy ablation was observed in all pigs. The MR-evident lesions were well confined within the targeted volume, without evidence of excessive brain edema or hemorrhage outside of the target zone. Histology revealed tissue homogenization in the ablation zones with a sharp demarcation between destroyed and unaffected tissue, which correlated well with the radiographic treatment zones on MRI. These results are the first to support the in vivo feasibility of tcMRgHt in the pig brain, enabling further investigation of the use of tcMRgHt for brain surgery.

Pelvicaliceal Volume and Fluid Temperature Elevation During Laser Lithotripsy.

Background: While high-power laser systems facilitate successful ureteroscopic treatment of larger and more complex stones, they can substantially elevate collecting system fluid temperatures with potential thermal injury of adjacent tissue. The volume of fluid in which laser activation occurs is an important factor when assessing temperature elevation. The aim of this study was to measure fluid temperature elevation and calculate thermal dose from laser activation in fluid-filled glass bulbs simulating varying calix/pelvis volumes. Materials and Methods: Glass bulbs of volumes 0.5, 2.8, 4.0, 7.0, 21.0, and 60.8 mL were submerged in a 16-L tank of 37°C deionized (DI) water. A 230-µm laser fiber extending 5 mm from the tip of a ureteroscope was positioned in the center of each glass bulb. Irrigation with 0, 8, 15, and 40 mL/min of room temperature DI water was applied. Once steady-state temperature was achieved, a Ho:YAG laser was activated for 60 seconds at 40 W (0.5 J × 80 Hz, SP). Temperature was measured from a thermocouple affixed to the external tip of the ureteroscope. Thermal dose was calculated using the Dewey and Sapareto t43 methodology. Results: The extent of temperature elevation and thermal dose from laser activation were inversely related to the volume of fluid in each model and the irrigation rate. The time to threshold of thermal injury was only 3 seconds for the smallest model (0.5 mL) without irrigation but was not reached in the largest model (60.8 mL) regardless of irrigation rate. Irrigation delivered at 40 mL/min maintained safe temperatures below the threshold of tissue injury in all models with 1 minute of continuous laser activation. Conclusions: The volume of fluid in which laser activation occurs is an important factor in determining the extent of temperature elevation. Smaller volumes receive greater thermal dose and reach threshold of tissue injury more rapidly than larger volumes.

Transcostal Histotripsy Ablation in an In Vivo Acute Hepatic Porcine Model.

PURPOSE: To determine whether histotripsy can create human-scale transcostal ablations in porcine liver without causing severe thermal wall injuries along the beam path. MATERIALS AND METHODS: Histotripsy was applied to the liver using a preclinical prototype robotic system through a transcostal window in six female swine. A 3.0 cm spherical ablation zone was prescribed. Duration of treatment (75 min) was longer than a prior subcostal treatment study (24 min, 15 s) to minimize beam path heating. Animals then underwent contrast-enhanced MRI, necropsy, and histopathology. Images and tissue were analyzed for ablation zone size, shape, completeness of necrosis, and off-target effects. RESULTS: Ablation zones demonstrated complete necrosis with no viable tissue remaining in 6/6 animals by histopathology. Ablation zone volume was close to prescribed (13.8 ± 1.8 cm3 vs. prescribed 14.1 cm3). Edema was noted in the body wall overlying the ablation on T2 MRI in 5/5 (one animal did not receive MRI), though there was no gross or histologic evidence of injury to the chest wall at necropsy. At gross inspection, lung discoloration in the right lower lobe was present in 5/6 animals (mean size: 1 × 2 × 4 cm) with alveolar hemorrhage, preservation of blood vessels and bronchioles, and minor injuries to pneumocytes noted at histology. CONCLUSION: Transcostal hepatic histotripsy ablation appears feasible, effective, and no severe injuries were identified in an acute porcine model when prolonged cooling time is added to minimize body wall heating.

Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound.

Histotripsy is the first noninvasive, non-ionizing, and non-thermal ablation technology guided by real-time imaging. Using focused ultrasound delivered from outside the body, histotripsy mechanically destroys tissue through cavitation, rendering the target into acellular debris. The material in the histotripsy ablation zone is absorbed by the body within 1-2 months, leaving a minimal remnant scar. Histotripsy has also been shown to stimulate an immune response and induce abscopal effects in animal models, which may have positive implications for future cancer treatment. Histotripsy has been investigated for a wide range of applications in preclinical studies, including the treatment of cancer, neurological diseases, and cardiovascular diseases. Three human clinical trials have been undertaken using histotripsy for the treatment of benign prostatic hyperplasia, liver cancer, and calcified valve stenosis. This review provides a comprehensive overview of histotripsy covering the origin, mechanism, bioeffects, parameters, instruments, and the latest results on preclinical and human studies.