High-frequency shock wave lithotripsy: stone comminution and evaluation of renal parenchyma injury in a porcine ex-vivo model.

BACKGROUND: The electrohydraulic high-frequency shock wave (Storz Medical, Taegerwilen, Switzerland) is a new way to create small fragments with frequencies up to 100 Hertz (Hz). This study evaluated the efficacy and safety of this method in a stone and porcine model. MATERIALS AND METHODS: BEGO stones were put in a condom in a specifically designed fixture treated with different modulations to see stone comminution. Standardized ex vivo porcine model with perfused kidneys with 26 upper and lower poles of 15 kidneys was treated with the following modulations: voltage 16-24 kV, capacitor 12 nF and frequency up to 100 Hz. 2000-20,000 shock waves were applied to each pole. The kidneys were perfused with barium sulfate solution (BaSO4) and x-ray was performed to quantify the lesions using pixel volumetry. RESULTS: There was no correlation between the number of shock waves and the powdering degree or the applied Energy and the grade of pulverization in the stone model. Regarding the perfused kidney model, the number of shock waves, applied voltage and frequency had no direct correlation with the occurrence of parenchymal lesions The detected lesions of the renal parenchyma were minimal, technical parameters had no significant impact and the lesions did not differ from the results of former experiments using 1-1.5 Hz in the same model. CONCLUSIONS: High-frequency shock wave lithotripsy can produce small stone fragments to pass in a very short time. The injury to the renal parenchyma is comparable to the results of the conventional SWL using 1-1.5 Hz.

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy.

Ultrasound-based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical study using ultrasound brain stimulation and first observations of long term effects are presented. Comprehensive feasibility, safety, and efficacy data are provided. They consist of simulation data, laboratory measurements with rat and human skulls and brains, in vivo modulations of somatosensory evoked potentials (SEP) in healthy subjects (sham controlled) and clinical pilot data in 35 patients with Alzheimer's disease acquired in a multicenter setting (including neuropsychological scores and functional magnetic resonance imaging (fMRI)). Preclinical results show large safety margins and dose dependent neuromodulation. Patient investigations reveal high treatment tolerability and no major side effects. Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to three months and correlates with an upregulation of the memory network (fMRI data). The results encourage broad neuroscientific application and translation of the method to clinical therapy and randomized sham-controlled clinical studies.

Blood clot disruption in vitro using shockwaves delivered by an extracorporeal generator after pre-exposure to lytic agent.

The standard methods for recanalyzing thrombosed vessels are vascular stenting or administration of thrombolytic drugs. However, these methods suffer from uncertain success rate and side-effects. Therefore, minimally-invasive ultrasound methods have been investigated. In this article, we propose to use shockwaves after pre-exposure to fibrinolytic agent for disrupting thrombus. Shockwaves were delivered by an extracorporeal piezocomposite generator (120 mm in diameter, focused at 97 mm, pulse length = 1.4 micros). In vitro blood clots, made from human blood, were placed at the focal point of the generator. The clots were exposed to shockwaves either with or without prior immersion in a solution of streptokinase. The percentage of lysed clot was determined by weighing the clot before and after treatment. The proportion of lysed clot increased with the pressure at the focus and with the number of shocks. A mean clot reduction of 91% was obtained for 42 MPa in 4-min treatment duration only, without using streptokinase. For a treatment of 2 min at 29 MPa, the clot reduction increased significantly (p < 0.01) from 47% without streptokinase to 82% when streptokinase was used prior to shockwaves. These results also showed no significant damage to streptokinase due to exposure to shockwaves. This study suggests that extracorporeal shockwaves combined with streptokinase is a promising pharmaco-mechanical method for treating occlusive thrombus, and should be confirmed by in vivo trials. Additional studies must also be conducted with other fibrinolytic agents, whose abilities to penetrate clots are different.

Feasibility of using ultrasound contrast agents to increase the size of thermal lesions induced by non-focused transducers: in vitro demonstration in tissue mimicking phantom.

Miniature flat ultrasound transducers have shown to be effective for a large variety of thermal therapies, but the associated superficial heating implicates developing original strategies in order to extend therapeutic depth. The goal of the present paper is to use ultrasound contrast agents (UCA) to increase remote attenuation and heating. Theoretical simulations demonstrated that increasing attenuation from 0.27 to 0.8 Np/cm at 10 MHz beyond a distance of 18 mm from the transducer should result in longer thermal damages due to protein coagulation in a tissue mimicking phantom. Contrast agents (BR14, Bracco, Plan-les-Ouates, Switzerland) were embedded in thermo-sensitive gel and attenuations ranging from 0.27 to 1.33 Np/cm were measured at 10 MHz for concentrations of BR14 between 0 and 4.8%. Thermal damages were then induced in several gels, which had different layering configurations. Thermal damages, 12.8mm in length, were obtained in homogeneous gels. When mixing contrast agents at a concentration of 3.2% beyond a first 18 mm-thick layer of homogeneous gel, the thermal damages reached 21.5mm in length. This work demonstrated that contrast agents can be used for increasing attenuation remotely and extending therapeutic depth induced by a non-focused transducer. Additional work must be done in vivo in order to verify the remote-only distribution of bubbles and associated increase in attenuation.

Delivery by shock waves of active principle embedded in gelatin-based capsules.

PURPOSE: Delivering a drug close to the targeted cells improves its benefit versus risk ratio. A possible method for local drug delivery is to encapsulate the drug into solid microscopic carriers and to release it by ultrasound. The objective of this work was to use shock waves for delivering a molecule loaded in polymeric microcapsules. MATERIAL AND METHODS: Ethyl benzoate (EBZ) was encapsulated in spherical gelatin shells by complex coacervation. A piezocomposite shock wave generator (120 mm in diameter, focused at 97 mm, pulse length 1.4 micros) was used for sonicating the capsules and delivering the molecule. Shock parameters (acoustic pressure, number of shocks and shock repetition frequency) were varied in order to measure their influence on EBZ release. A cavitation-inhibitor liquid (Ablasonic) was then used to evaluate the role of cavitation in the capsule disruption. RESULTS: The measurements showed that the mean quantity of released EBZ was proportional to the acoustic pressure of the shock wave (r2 > 0.99), and increased with the number of applied shocks. Up to 88% of encapsulated EBZ could be released within 4 min only (240 shocks, 1 Hz). However, the quantity of released EBZ dropped at high shock rates (above 2Hz). Ultrasound imaging sequences showed that cavitation clouds might form, at high shock rates, along the acoustic axis making the exposure inefficient. Measurements done in Ablasonic showed that cavitation plays a major role in microcapsules disruption. CONCLUSIONS: In this study, we designed polymeric capsules that can be disrupted by shock waves. This type of microcapsule is theoretically a suitable vehicle for carrying hydrophobic drugs. Following these positive results, encapsulation of drugs is considered for further medical applications.

Developing an interstitial ultrasound applicator for thermal ablation in liver: results of animal experiments.

BACKGROUND: In this project, an interstitial ultrasound applicator was developed for the treatment of primary and secondary cancers of the liver. Experiments on animals were used to check the destructive capabilities of this probe within the hepatic parenchyma of the pig in vivo, with a study of the physical parameters of the ultrasound treatment. In parallel, the possibility of visualizing the lesions induced by means of ultrasound imaging was also studied. MATERIALS AND METHODS: Thirteen pigs were used in this project, which had received the prior approval of the ethics committee of Lyon Veterinary School. Ultrasound lesions were performed by varying the physical parameters of the treatment (acoustic intensity and shot time) with the aim of obtaining larger and larger areas of destruction. An operative device was developed to ensure precision in treatments. Two types of lesions were performed: elementary lesions corresponding to single shots at 40 degrees to 50 degrees rotation intervals, and cylindrical lesions obtained by a continuous rotary deployment of the probe. The effect of hepatic pedicle clamping on the size of ultrasound lesions was studied. The aspect and dimension of the lesions were analyzed by means of operative ultrasound imaging and macroscopic examination. Histological analysis showed the impact of the treatment on the hepatic parenchyma. RESULTS: This work made it possible to study the elementary ultrasound lesions produced by our probe. Seventy elementary ultrasound lesions were analyzed. Treatments could be performed on all pigs without any difficulty. There were no operative incidents. The ultrasound-induced elementary lesions showed complete necrosis, with lesion length of up to 37 mm obtained without resort to pedicle clamping; this must be considered as a radius of the final lesion obtained over a complete rotary deployment (360 degrees ), then a diameter of 7 cm of thermal ablation can theoretically be obtained. The effect of pedicle clamping was studied and showed improvement of the lesion length. Results of continuous rotary deployment of the probe were encouraging. Operative ultrasound imaging proved to be a simple tool for directing and positioning the applicator in the target zone on the one hand and which, on the other hand, enabled accurate, real-time visualization of the ultrasound lesions. On histological analysis, the ultrasound-induced necrosis was complete and well defined. CONCLUSION: This work shows that it is feasible to treat cancers of the liver using interstitial ultrasound probe. Thermal damage obtained on the hepatic parenchyma of pigs in vivo is complete and can be monitored using simple diagnostic ultrasound. The ultrasound parameters can be adapted to obtain destruction of variable size.