Artificial Kidney Stones Research Articles

Fabrication of acoustically and physically validated artificial stones to natural kidney stones under shock waves and laser lithotripsy

To present an efficient method for fabricating artificial kidney stones with acoustic and physical properties to assess their fragmentation efficiency under shock waves and laser lithotripsy for very hard stones. The mixture ratio of super-hard plaster and water was adjusted to produce artificial kidney stones for comparison with > 95% human genuine calcium oxalate monohydrate (COM) and uric acid (UA) stones. Acoustic and physical properties, such as wave speed, stone hardness, density, compressive strength, and stone-free rates under shock-wave and laser lithotripsy, were assessed. The longitudinal wave speed of artificial stones prepared at a plaster-to-water ratio of 15:3 closely matched that of COM stones. Similarly, the transverse wave speed of artificial stones prepared at a plaster-to-water ratio of 15:3 to 15:5 aligned with that of COM stones. Stone fragmentation using shock-wave of artificial stones with mixed ratios ranging from 15:3 to 15:5 resembled that of COM stones. The Vickers hardness was similar to that of artificial stones produced with a mixing ratio of 15:3, similar to that of COM stones, while that of artificial stones produced with a mixing ratio of 15:5 was similar to that of UA stones. Density-wise, artificial stones with mixing ratios of 15:4 and 15:5 resembled COM stones. Compressive strength test results did not confirm the similarity between natural and artificial stones. The stone fragmentation using laser showed that stones produced with higher moisture content at a mixing ratio of 15:6 were similar to COM stones. This novel method for fabricating artificial kidney stones could be used to provide reliable materials for lithotripsy research.

1256 Fabricating Artificial Kidney Stones of Different Physical Properties for Ex Vivo Experimentation

Abstract Introduction There have been several new technologies introduced recently for lithotripsy. The optimal settings of these devices are unknown for different kidney stone densities. This study aims to develop artificial kidney stones for ex vivo studies. Method BegoStone was prepared with a powder to water ratio (by weight) ranging from 15:3 to 15:6. The phantoms' acoustic properties were characterised by using an ultrasound transmission technique, from which the corresponding mechanical properties can calculated based on elastic wave theory. Results The measured parameters for BegoStone phantoms of different water contents were assessed with regard to longitudinal wave speed & density. If transverse wave speeds were measured then longitudinal acoustic impedance, transverse acoustic impedance, Young's modulus, bulk modulus, and shear modulus can be derived. Longitudinal (CL (m/s)) and density (ρ (Kg/m3)) of BegoStone phantoms with different powder to water ratios corresponded to the known properties reported in natural kidney stones (Calcium Oxalate Monohydrate, Brushite, Uric acid and Struvite). A BegoStone water ratio of 15:3 had similar properties to Calcium Oxalate Monohydrate, 15:4 to be similar to Brushite, 15:5 was similar to Uric acid, and 15:6 was similar to Struvite. Conclusions This BegoStone preparation method can be used to fabricate artificial stones with physical properties matched with those of natural kidney stones of various chemical compositions.

POS-459 EXAMINING THE EFFECT OF CALCULI SHAPE AND DIMENSION ON URETER OUTFLOW RATES USING AN ARTIFICIAL 3D PRINTED KIDNEY

Kidney stone disease is a urological disorder that affects about 12% of the world population. A deeper understanding of the underlying etiologies and effects which this condition generates, such as alterations in renal hemodynamics, is essential for developing models to study this disorder. Several experimental approaches have been employed, and recent developments in 3D printing offer an exciting opportunity to mimic impediments to urine flow characteristics caused by calculi. Here we present one such simplified model. A 3D artificial renal model was developed using SolidWorks 2019 software ( to provide the template (Figure 1a) for the bioprinted scaffolds (Figure 1b). Spherical and elliptical kidney stones, ranging from 0 to 6 mm, mimic calculi embedded in the artificial ureter designed with flexible plastic tubing (Figure 1C). A mechanical circulation pump was then used to induce urine flow (Figure 1D). Flow velocities were obtained using different geometries of 3D printed kidney stones. Flow magnitude and characteristics were compared to understand the effect of having different geometries on the distribution of urinary flow (Figure 1E). The minimum flow velocities for spherical and elliptical stones were 0 and 34.1 cm/sec for 5 and 4 mm stone sizes, respectively. Surprisingly, elliptical kidney stones showed an increase in the flow velocity at the maximum elliptical stone size of 6 mm (54.39 cm/sec) due to the nature of its geometry. For the case of the spherical shape, it converged to (0 cm/sec). Figure 1. The 3D artificial renal model outlining: SolidWorks 2019 organ template (a); (b) the bioprinter model; (c) spherical and elliptical artificial kidney stones embedded in the ureter; (d) mechanical circulation pump was then used to induce urine flow; and an outline of the variations in volumetric floe rate with calculi size. The results from this study provide insight on ways to create simplified artificial organ models that simulate hemodynamic observed in Kidney stone disease and can be used to develop more sophisticated reverse-engineered artificial 3D-printed kidney models.

Calcium Oxalate Crystallization: Influence of pH, Energy Input, and Supersaturation Ratio on the Synthesis of Artificial Kidney Stones.

The removal of kidney stones can lead to small residual fragments remaining in the human body. Residual stone fragments can act as seeds for kidney stone crystallization and may necessitate another intervention. Therefore, it is important to create a consistent model with a particle size comparable to the range of kidney stone fragments. Thus, the size-determining parameters such as supersaturation ratio, energy input, and pH value are examined. The batch crystallizations were performed with supersaturation ratios between 5.07 and 6.12. The compositions of the dried samples were analyzed with Raman spectroscopy, infrared spectroscopy, and X-ray diffraction (XRD). The samples were identified as calcium oxalate monohydrate with spectroscopic analysis, while calcium oxalate dihydrate being the most prominent crystalline species at all supersaturation ratios for the investigated conditions. The aggregate size, obtained with analytical centrifugation, varied between 2.9 and 4.3 μm, while the crystallite domain size, obtained from XRD, varied from 40 to 61 nm. Our results indicate that particle sizes increase with increasing supersaturation, energy input, and pH. All syntheses yield a high particle heterogeneity and represent an ideal basis for reference materials of small kidney stone fragments. These results will help better understand and control the crystallization of calcium oxalate and the aggregation of such pseudopolymorphs.

Abstract 32 - Fabrication of artificial kidney stones of different physical properties for ex vivo experimentation

Abstract 32 - Fabrication of artificial kidney stones of different physical properties for ex vivo experimentation

Photothermal nanoparticles for ablation of bacteria associated with kidney stones

Objective To determine whether photothermal polymer nanoparticles (NPs) can interface with bacteria associated with kidney stones, generate heat when stimulated with near infrared (NIR) light, and aid in reducing bacterial burden. Methods Two types of kidney stones, artificial, and those removed during percutaneous nephrolithotomy (PCNL), were inoculated with Escherichia coli (E. coli) and then incubated with NPs composed of FITC-labeled Poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b′]-dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). Association of the PCPDTBSe NPs was evaluated using fluorescence microscopy. Infected stones were incubated with NPs and exposed to 800 nm light to generate temperature increases from 25.4 to 68.6 °C on the stones. Following photothermal treatment, the stones were homogenized and the bacteria was enumerated via colony counting assays to evaluate the bactericidal effect. The photothermal effect was also evaluated using scanning electron microscopy of the treated biofilms. Results Both kidney stone types sequestered E. coli. Control stones and stones treated with laser only had growth of numerous bacterial colonies, while stones exposed to NPs and laser grew significantly less, or none (p = 0.02). Conclusions The polymer NPs interface with E. coli on artificial and patient-derived kidney stones, and they can impart a bactericidal effect, when stimulated with NIR to generate heat. This technique may possibly be extended to treating infected kidney stones in patients.

In-Vitroanti-Urolithiatic Activity of Theriophonum Minutum and Remusatia Vivipara

Kidney stone is a very common disease worldwide threat. The calcium oxalate is the important compound of calculi formation in the urinary tract. Traditional studies on use of herbal based medicinal plants for treating severe disease is satisfying its bad to advanced world . In this regard, the study was analyzed with an objective to carry out the role of Theriophonum minutum and Remusatia vivipara leaves extract in different solvents to reduce stone formation and to find out the concentration of medicinal plant extract exhibit dissolution rate of kidney stones In dissolution studies, the extract of Remusatia vivipara has greater ability to dissolve artificial calcium stones and kidney stones rather than the standard drug. Calcium oxalate crystal formation was stimulated by the sodium oxalate solutions. The effect of different extract concentration was applied to measure the dissolution rate, turbidity, nucleation aggregation assay . The extract of Theriophonum minutum and Remusatia vivipara reflected the blocking action in both of nucleation and aggregation to better level

A multi-element HIFU array system: Characterization and testing for manipulation of kidney stones

Most progress in acoustic trapping and levitation has been achieved with the use of multiple sound sources, standing waves, and low density or very small objects. Repositioning kidney stones in the human body is an important clinical application where acoustic levitation could be employed; however, it requires manipulation of larger and heavier objects. The goal of this work was to calibrate the acoustic output of a 1.5-MHz, 256-element array designed in our laboratory for HIFU research, which is also capable of generating vortex beams to manipulate mm-sized objects in water and to move them in any direction without moving the source. Electrical circuits were developed for matching each element of the array to an output channel of a Verasonics ultrasound engine to allow for efficient power transfer to the transducer. Acoustic holography was used to calibrate and equalize outputs across all channels. Manipulation of artificial kidney stone targets made of plastic, glass, or cement (2—8 mm) and comparable in size to or larger than the wavelength in water by electronic steering of the vortex beam lateral to the acoustic axis was demonstrated. [Work supported by NIH P01 DK043881, K01 DK104854, R01 EB007643, and NSBRI through NASA NCC 9-58.]

Generation of different types of surface acoustic waves by shock wave-Stone interaction

The generation of different types of surface acoustic waves (SAWs) in lithotripsy is investigated by numerical simulations using COMSOL, considering either the case of a weakly focused shock wave as an incident plane wave (in the focal plane) in shock wave lithotripsy (SWL) or a spherically divergent shock wave produced by a spark discharge in Nano Pulse Lithotripsy (NPL). The interaction of these two types of shock waves with an artificial kidney stone immersed in water may generate three different types of SAWs: namely, Scholte wave, acoustic surface evanescent wave (ASEW), and leaky Rayleigh wave (LRW). In particular, we examined the generation of SAWs on a flat, cylindrical, or spherical surface under different incident angles. It was found that the geometry and acoustic properties of the stone could significantly influence the types of SAWs generated and the resultant peak tensile stress produced at the stone-water boundary. Comparison with experimental measurements (i.e., Schlieren and photoelastic imaging) and stone fracture will also be made. [Work supported by NIH through 5R37DK052985-20.]

Acoustic stone localization during lithotripsy.

It is desirable to mitigate damage to kidney tissue induced by shock waves administered during lithotripsy. Stone movement due to patient respiration causes a fraction of the shock waves to miss the stone. The goal here is to ensure that shock waves are delivered to the kidney only when the kidney stone is in the focal region of the lithotripter. We present the design of a collar with an array of ultrasound transducers that can be retrofitted to a clinical lithotripter. The transducers are used in a pulse‐echo mode and a hybrid technique combining numeric time‐reversal and MUSIC (MUltiple‐SIgnal‐Classification) is employed to determine the location of a kidney stone relative to the focus of the lithotripter. A model of the acoustic collar was used to select system parameters including the transducer count, center frequency, and transducer placement. The performance of the collar was assessed by translating artificial kidney stones in water and using porcine body wall as an aberrating layer. Performance wi...

A simple method for fabricating artificial kidney stones of different physical properties

A simple method for preparing artificial kidney stones with varying physical properties is described. BegoStone was prepared with a powder-to-water ratio ranging from 15:3 to 15:6. The acoustic properties of the phantoms were characterized using an ultrasound transmission technique, from which the corresponding mechanical properties were calculated based on elastic wave theory. The measured parameters for BegoStone phantoms of different water contents are: longitudinal wave speed (3,148-4,159 m/s), transverse wave speed (1,813-2,319 m/s), density (1,563-1,995 kg/m(3)), longitudinal acoustic impedance (4.92-8.30 kg/m(2) s), transverse acoustic impedance (2.83-4.63 kg/m(2) s), Young's modulus (12.9-27.4 GPa), bulk modulus (8.6-20.2 GPa), and shear modulus (5.1-10.7 GPa), which cover the range of corresponding properties reported in natural kidney stones. In addition, diametral compression tests were carried out to determine tensile failure strength of the stone phantoms. BegoStone phantoms with varying water content at preparation have tensile failure strength from 6.9 to 16.3 MPa when tested dry and 3.2 to 7.1 MPa when tested in water-soaked condition. Overall, it is demonstrated that this new BegoStone preparation method can be used to fabricate artificial stones with physical properties matched with those of natural kidney stones of various chemical compositions.

Kidney stone localization in vitro using multiple-signal-classification.

During shock wave lithotripsy, respiration and patient movement result in motion of a kidney stone. It has been estimated that 50% of the shock waves miss the stone. The misshots result in damage to the tissue with no therapeutic benefit. Here we employed a ring array of seven piezo-electric elements with center frequency of ∼600 kHz to track stones in vitro. Each element was used to transmit in turn, and the individual waveforms received on all elements were recorded. The Fourier transform of these data gives the multistatic response matrix, whose largest eigenvalues represent the dominant scatterers in the medium. The associated eigenvectors were employed by the multiple-signal-classification (MUSIC) method to generate a scattering indicator image from which scatterer locations were determined. We tested MUSIC’s applicability to track artificial kidney stones in water or with a tissue phantom. Single targets were tracked with an accuracy of 4 mm. A single stone resulted in three eigenvalues and therefore the seven element array could track two targets. Two targets were resolved for separations of 10 mm. The results indicate that MUSIC can be employed to track kidney stones although more elements would be required to track multiple fragments. [Work supported in part by NIH DK-43881].

The role of energy density and acoustic cavitation in shock wave lithotripsy

Today a high percentage of urinary stones are successfully treated by extracorporeal shockwave lithotripsy (SWL); however, misconceptions regarding fragmentation mechanisms, as well as treatment parameters like dose, applied energy and focal area are still common. A main stone comminution mechanism during SWL is acoustic cavitation. The objective of this study was to analyze the influence of cavitation and energy density on stone fragmentation. A research lithotripter was used to expose a large set of artificial kidney stones to shock waves varying different parameters. Hundreds of pressure records were used to calculate the energy density of the lithotripter at different settings. Results indicate that energy density is a crucial parameter and that better SWL treatment outcomes could be obtained placing the calculus at a prefocal position.

Treatment Time Reduction Using Tandem Shockwaves for Lithotripsy: AnIn VivoStudy

Reducing extracorporeal shockwave lithotripsy (SWL) time by increasing the shockwave rate of the lithotripter has been tested in the past; however, basic research and treatment outcomes revealed that this is not convenient. The purpose of this study was to use an animal model to demonstrate that SWL treatment time can be reduced significantly without sacrificing stone fragmentation efficiency using tandem shockwaves. A tandem research lithotripter was used to treat 50 artificial kidney stones implanted into the kidneys of 50 rabbits. Standard single-pulse and tandem shockwaves were compared in two different scenarios: Without a fluid-filled expansion chamber and with a fluid-filled expansion chamber surrounding the stone. The presence of fluid surrounding the stone enhances fragmentation in both the standard and tandem modes. No significant difference in fragmentation efficiency was recorded between the standard and tandem SWL with stones surrounded by fluid; however, the treatment time with tandem shockwaves was reduced by 50%. Significantly shorter SWL treatments may be possible in the future using tandem shockwaves on urinary stones that are surrounded by fluid.

Kidney stone tracking in vitro using an acoustic triangulation paradigm.

During shock wave lithotripsy, stones undergo motion which can place them outside the focal zone of the lithotripter. This results in shock waves being delivered that do not impact the stone but may injure tissue. Tracking stones using diagnostic ultrasound imaging (∼4 MHz) has proven to be challenging. Here we employed an array of seven relatively low‐frequency (∼600 kHz) elements to detect scattered signals from an artificial kidney stone in the presence of a tissue phantom. Using an optimization routine, the time of flight to each element and array geometry were used to determine the most likely location of the stone. A comparison of threshold crossing and cross‐correlation for detecting signal arrival indicated that while the former yielded faster computation time, the latter was more robust to noise. Stone position was determined to within 2 mm for locations within 10 mm of the focus. For distances beyond 10 mm, the optimization routine was not able to reliably predict stone location but could indicate that the stone was not within the focal region. [Work supported in part by NIH.]

The Importance of an Expansion Chamber During Standard and Tandem Extracorporeal Shock Wave Lithotripsy

It is known that extracorporeal shock wave lithotripsy (SWL) may be improved by increasing cavitation using tandem shock waves. However, fluid is needed for the cavitation to work. The purpose of this research was to evaluate the importance of a fluid-filled expansion chamber in enhancing stone fragmentation during standard and tandem SWL. A piezoelectric lithotripter was modified to generate tandem shock waves. Artificial kidney stones inserted in vitro into the parenchyma of a pig kidney were exposed to either standard or tandem shock waves. Stones in one group were placed inside a small finger cot filled with water before they were introduced into the kidney. Stone fragments were strained through a mesh, dried, and weighed. Water surrounding the stones always improved stone fragmentation. The best results were achieved using tandem shock waves at a delay of 250 micros. A fluid-filled chamber surrounding the stone is essential for good SWL outcome. Tandem shock waves are more efficient than standard shock waves only if the stone is surrounded by fluid.

Interaction of Intracorporeal Lithotripters with Proteus mirabilis Inoculated Inside Artificial Calcium and Struvite Stones

Renal calculi may contain bacteria that can remain active inside the stone and produce bacteremia and/or endotoxemia after lithotripsy. Urinary tract infection associated with urinary stones represents high morbidity. The purpose of this research was to use novel artificial struvite stones inoculated with living bacteria and to study the effect of four different intracorporeal lithotripters on bacterial inactivation after in vitro lithotripsy. Two types of artificial kidney stone models (calcium sulphate and mixed struvite-calcium sulphate) were manufactured and infected with Proteus mirabilis. Stones were fractured using either electrohydraulic, laser, ultrasonic, or pneumatic lithotripters. Bacterial viability was determined before and after the lithotripsy. Bacterial inactivation was not affected by the stone matrix; ie, calcium or struvite. The four tested lithotripters were almost equally efficient at reducing the viability of P mirabilis in both the low and the high energy setting. We were able to obtain novel artificial struvite stones infected with bacteria. Intracorporeal lithotripters are efficient at reducing the viability of P mirabilis in vitro. Tested stone materials play a minor role regarding inactivation. Whether the bactericidal effect reported is desirable or not is still to be answered, because the presence of endotoxin from cell lysis may increase the risk of urosepsis.

Interaction of Shockwaves with Infected Kidney Stones: Is There a Bactericidal Effect?

Many calculi contain bacteria, which can remain active inside kidney stones and cause infection after lithotripsy. Reduction in renal infections after extracorporeal shockwave lithotripsy has been observed; however, results are controversial, and no information on the effect of shockwaves on bacteria inside kidney stones has been reported. The purpose of this research was to study whether bacteria inside kidney stones can be inactivated by shockwaves. A series of infected artificial kidney stones were exposed in vitro to either 90 or 400 shockwaves using a research electrohydraulic or a commercial piezoelectric lithotripter. Two types of stones (soft and hard) were manufactured by mixing gypsum cement and Vel-mix-stone with water. Half of the stones were inoculated with Salmonella typhimurium. The suspension containing stone powder and bacteria was inoculated on agar plates and incubated. Bactericidal action was defined as the logarithmic viability reduction. About 95% of the bacteria were inactivated with 400 shockwaves using the electrohydraulic lithotripter; however, most of the damage was associated with the electromagnetic emission (ultraviolet radiation and visible light) generated at the spark gap. After 2730 shockwaves to stones placed inside a black polypropylene bag, about 29% and 14% of all bacteria were inactivated with the piezoelectric and the electrohydraulic lithotripter, respectively. In this case, the electromagnetic radiation was blocked by the black bag. Bacteria inactivation is possible by in vitro shockwave application; however, according to our results, no significant bactericidal effect is expected during extracorporeal shockwave lithotripsy.

Short‐ and long‐delay tandem shock waves for application in medicine

Long‐delay tandem shock waves with an inter‐pulse delay between about 200 and 500 microseconds have shown to enhance fragmentation of artificial kidney stones during in vitro and in vivo extracorporeal shock wave lithotripsy (SWL) in the past. Cell‐permeabilization and inactivation of bacteria using tandem shock waves have also been proposed. The purpose of this research was to study the influence of short‐delay (less than 50 microseconds) tandem shock waves on cavitation induced damage to kidney stones during SWL. A multipurpose piezoelectric shock wave generator was designed to generate shock waves at variable delays. The effect of short‐ and long‐delay dual‐pulse shock waves on the surface of artificial kidney stones was evaluated by microscopy. An adequate selection of delays was possible by means of a numerical model and high speed photography. Stone fragmentation was compared to that of standard (single‐pulse) shock waves. Our results indicate that specific combinations of short‐ and long‐delay tand...

Inactivation of bacteria inoculated inside urinary stone-phantoms using intracorporeal lithotripters

Intracorporeal lithotripsy is used to treat a high percentage of urinary calculi. Urinary calculi may contain bacteria, which might cause septicemia after lithotripsy; however, little is known about the effects of lithotripters on the viability of microorganisms inside renal calculi. The objectives of this study were to evaluate the bactericidal effect, and the potential effect on intra-bacterial protein release of four different intracorporeal lithotripters on Escherichia coli (E. coli) inoculated inside artificial kidney stones. An electrohydraulic, a pneumatic, an ultrasonic, and a holmium-laser lithotripter were used to pulverize a set of infected kidney stones inside a test tube containing a saline solution. Two different energy levels were tested per lithotripter. The stones were manufactured by mixing gypsum cement and Vel-mix-stone with a suspension containing E. coli. Results were analyzed by analysis of variance. The release of intracellular protein was measured with a spectrophotometer. Bacteria inactivation was observed with all lithotripters. The highest percentage of inactivated bacteria was obtained with the electrohydraulic lithotripter. The smallest effect was observed using the holmium-laser lithotripter. A relatively high amount of intracellular protein was released into the saline solution after stone pulverization. Intracorporeal lithotripters inactivate a high percentage of bacteria during stone comminution; however, intracellular protein is released, increasing the probability of septicemia.