High-intensity focused ultrasound transducers suitable for endoscopy: feasibility study in rabbits.
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Animals↗
Biomedical subjects
D Cathignol
Publications and source records attributed to D Cathignol.
Destruction of rat exocrine pancreatic tissue by photodynamic therapy.
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Amylases↗
A piezocomposite shock wave generator with electronic focusing capability: application for producing cavitation-induced lesions in rabbit liver.
In this work, a piezocomposite shock wave generator with electronic focusing capability is presented. The system is composed of a bidimensional array and its electronic hardware. The array is composed of 274 independent piezocomposite transducers arranged in a spherical shell of 280 mm in diameter and focused at 190 mm from its surface. The electronic hardware includes 274 x 6.6 kV distinct impulse generators. For the purpose of performing the electronic steering of shock waves, the delay time of each channel can be adjusted from 100 ns to 100 microseconds in steps of 100 ns. In order to enhance the effect of cavitation at the focus for the purpose of tissue destruction, the pressure-time waveform starts with a half cycle of negative pressure with a peak amplitude of about -150 x 10(5) Pa, followed by a very steep shock front with a positive peak pressure > 1000 x 10(5) Pa and a rise time of about 10 ns. Using this generator, the cavitation-induced lesions in rabbit liver were studied. To obtain a predefined lesion volume, two methods of scanning were used: mechanical and electronic. Comparison of the lesions obtained by these two methods shows that they have identical macroscopic and histological characteristics, which justify the feasibility of electronic beam steering of shock waves in tissue destruction applications.
Animals↗
High-efficiency shock-wave generator for extracorporeal lithotripsy.
In extracorporeal lithotripsy, the electro-acoustic efficiency of electrohydraulic generators is limited by the inductance of the electrical discharge circuit. A new shock-wave generator is described that uses a coaxial discharge line enabling electro-acoustic efficiency to be greatly increased. The line is built using a para-electric ceramic with a relative dielectric constant of 1700, manufactured for use in high-voltage impulse mode. A coaxial spark gap, with minimal inductance, has been developed to obtain the triggered breakdown of the discharge line. Shock waves are created with a coaxial electrode plugged directly into the spark gap and immersed in an electrolyte of degassed saline. Electrode gap and electrolyte resistivity are adjusted to match the resistivity of the electrolyte volume between the underwater electrodes to the characteristic impedance of the line. The discharge line generates in the medium a rectangular current pulse with an amplitude of about 6000 A and a rise time of 50 ns. Compared with conventional generators, measurements of the expansive peak pressure pulse show an increase of 105% at 10 kV, 86.5% at 12 kV and 34.5% at 14 kV charging voltage. Electro-acoustic efficiency is found to be 11% instead of 5.5% for a conventional discharge circuit.
Acoustics↗
Treatment of prostate cancer with transrectal focused ultrasound: early clinical experience.
OBJECTIVES: To evaluate the efficacy of transrectal focused ultrasound on localized prostatic cancer. METHODS: Fourteen patients (mean age 72.5 years) with clinical stage T1 (3) and T2 (11) prostatic cancers, who were not suitable candidates for surgery were treated. The mean PSA pretreatment level was 12 +/- 10 ng/ml (Hybritech). The device used (Ablatherm, Technomed M.S.) combines a 2.25-MHz therapy transducer and a 7.5-MHz transrectal biplane ultrasound scanner probe (linked to a software enabling the operator to determine precisely the zone of the prostate to be treated. The prostate was treated in one (3 patients), two (7 patients) or three sessions (4 patients) under spinal (25 sessions) or general anesthesia (4 sessions). RESULTS: Complications occurred in 9 of the 14 patients (64%): early complications occurred in 6 (rectal burns 3, urinary retention 2, transient incontinence 1) and late complications in 5 (incontinence 2, bladder neck stenosis 3). The median PSA NADIR value (1.79 +/- 2.35 ng/ml) was achieved at 6 months and the final PSA value was 2.94 +/- 3.27 ng/ml (mean follow-up 380 days). Control biopsies demonstrated coagulative necrotic lesions of the treated prostate zones with secondary development into fibrosis. No residual cancer was observed in 7 patients after several random sextant biopsies. Residual cancer was found in 7 patients: 4 required complementary treatment (orchidectomy 2, external beam radiation therapy 2). Adjuvant therapy was deferred in 3 patients with stable PSA values under 2 ng/ml. CONCLUSIONS: A satisfactory local control with negative control biopsies was achieved in 50% of the cases in this pilot study. However, this therapy is an investigational procedure: long-term follow-up will be necessary to confirm these early results.
Aged↗
Venous thrombosis generation by means of high-intensity focused ultrasound.
Sclerotherapy of superficial varicose veins is now performed with chemical agents since physical agents have given only poor clinical results. We investigated the possibility of using high intensity focused ultrasound energy to achieve this goal in an animal model, the rat femoral vein. A specially designed probe delivering ultrasonic energy at a central frequency of 7.31 MHz was constructed and evaluated. Femoral veins of six rats were surgically exposed to a set of between four and seven 3-s exposures at 1-mm increments at a power level of 167 W/cm2. At 2 days following the irradiation, control veins were patent while occlusive thrombus was documented by Doppler flow and histological studies in all six of the irradiated veins. No damage to the surrounding soft tissues was noted. We concluded that high-intensity focused ultrasound can be used to induce thrombosis in this animal model.
Animals↗
Electronic beam steering of shock waves.
Shock-wave generators are now currently used for the treatment of renal stones. In all these generators the focal zone is determined by their geometrical parameters. We propose, for the first time, a piezocomposite shock-wave generator with electronic focusing. The system is composed of a two-dimensional array and its electronic hardware. The array is composed of 121 independent piezocomposite transducers arranged in a spherical shell 20 cm in diameter and focused at 190 mm. The electronic hardware includes 121 x 6 kV-impulse generators. The interdelay of each channel can be adjusted between 10 ns to 100 microseconds by steps of 10 ns. The results show: the use of composite material is possible for the generation of high amplitude pressure waves; the pressure-voltage relationship is linear up to a pressure of about 28 x 10(5) Pa at the transducer front face; the material can be used for a long period of time; i.e., after one million shocks, no decrease in sensitivity, no alteration in its electrical behaviour and no time wave form distortion were observed. Electronic focusing is efficient in an ellipsoidal region of about 4 cm in diameter and 6 cm in length. The pressure in the focal zone is about 600 x 10(5) Pa.
Acoustics↗
Extracorporeal high-intensity focused ultrasound for VX2 liver tumors in the rabbit.
High-Intensity Focused Ultrasound (HIFU) can produce radical tissue necrosis. We wanted to assess tumor destruction, proliferation, and tumorigenesis after HIFU, in an animal model of hepatic tumor. New Zealand rabbits bearing VX-2 solitary liver tumors were treated with extracorporeal HIFU under ultrasound (US) guidance and standardized conditions. Groups differed only for the administration of either one or two consecutive HIFU procedures. Tissue destruction was assessed by stereomicroscopy and planimetry, cell proliferation was estimated by in vivo intra-arterial injection of 1200 muCi [3H]thymidine, and tumorigenesis was tested by reimplantation of treated or untreated pieces of liver tumors into the thighs of nontumor-bearing animals. Mortality was 0. Tumor destruction rates were 76.3% +/- 16% after one procedure and 94.2% +/- 7.3% after two procedures. Nuclear staining was heavy in control tumors and was absent in treated tumors. Untreated hepatic tumors induced measurable tumors at 3 weeks in thighs of all recipients, 7.8 +/- 2.4 cm3 in volume. Hepatic tumors treated with one HIFU procedure induced tumors in the thigh of recipients in 31.3% of cases (0.47 +/- 0.06 cm3), and those treated with two HIFU procedures induced tumors in 0% even after 8 weeks of follow-up. In conclusion, HIFU allows a noninvasive approach to the destruction of liver tumors in this model, with little toxicity but significant effects on proliferation and tumorigenesis. The repetition of HIFU procedures may improve results.
Animals↗
Increased chemocytotoxicity to colon cancer cells by shock wave-induced cavitation.
BACKGROUND/AIMS: Cavitation has been shown to hinder colon cancer cell proliferation in vitro. This study aimed at investigating the interest of combining cavitation and cytotoxic drugs in vitro. METHODS: HT-29 cells were exposed in suspension to cavitation (shock waves plus bubbles) before 5-fluorouracil (FUra) administration. Cytotoxicity was studied by means of clonogenic survival, cell proliferation by [3H]deoxyuridine ([3H]dUdR) incorporation, and influence of the treatments on the cell cycle by cytofluorimetry; the effects of cavitation on RNA incorporation of FUra, cell permeability, and activity of thymidilate synthetase (TS) were also studied. RESULTS: A preliminary exposure to cavitation (as compared with FUra alone) induced decreased colony formation (by up to 2 log in certain conditions) and colony size. Cavitation alone induced increased incorporation of [3H]dUdR during 48 hours and stimulated TS activity, but in the presence of FUra, the concentration of the drug that causes 50% inhibition of control cell growth for [3H]dUdR incorporation was reduced by up to 1 log, and TS inhibition was increased after cavitation as compared with FUra alone. RNA incorporation of [14C]FUra was increased by cavitation, as a consequence of altered cell permeability rather than a direct RNA effect. Seventy-two hours after treatment, cavitation plus FUra decreased by more than 50% the S-phase fraction and also inhibited mitosis. CONCLUSIONS: Submitting HT-29 cells to cavitation before treatment by FUra significantly increases the effects of the drug. The action of both agents appears to be partially synergistic with a cycle specificity.
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On the spectral properties of Doppler thread phantoms.
It is shown that some of the threads used in Doppler phantoms have a repetitive structure which leads to peaks in the angular distribution of the backscattered power at beam axis-to-flow angles of theta = 90 degrees and approximately theta = 70 degrees. This nonuniform scattering does not significantly interfere with modelling the Doppler spectrum peak as a function of velocity and beam-to-thread angle, but makes it impossible to model the spectral width as a function of these parameters. A new plaited structure is described which has a periodicity too small to lead to subsidiary reflection peaks, and which has a more uniform backscattering profile than the other threads studied.
Blood Flow Velocity↗
Focused liver ablation by cavitation in the rabbit: a potential new method of extracorporeal treatment.
A new device was used to achieve focused tissue ablation by shockwave induced cavitation. The device produced a half cycle of negative pressure followed by a shock wave, thus enhancing cavitation. Twenty eight New Zealand rabbits were treated. Therapeutic ultrasound was targeted at the centre of the liver under ultrasound guidance. The focal volume was scanned with a computer operated x-y-z micropositioner. The number and frequency of bursts as well as the distance between two x-y-z displacements were preselected. The relation of tissue ablation seen to preselected parameters, effects on surrounding tissues, biological side effects, and mode of healing were studied. Macroscopy, planimetry, and quantitative microscopy were used. Focused and homogeneous tissue ablation was achieved within well defined limits. Maximal tissue ablation was seen in the centre of the target. Liver surrounding the target remained unaffected. Lesions were made of a-cellular spots surrounded by disorganised rims of necrotic hepatocytes; 24 hours after treatment, the changes (mean (SEM)) in alanine transaminase and haemoglobin were +225 (36)% and -2.4 (2)% respectively. Serum transaminases, haemoglobinaemia, and packed cell volume were normal 21 days after treatment and the target area was replaced by a fibrous scar. It is concluded that ultrasound cavitation may achieve extracorporeal intrahepatic tissue ablation inside a predetermined target. This technique should now be tested in an animal hepatic tumour model.
Alanine Transaminase↗
Characterization of extracorporeal ablation of normal and tumor-bearing liver tissue by high intensity focused ultrasound.
Treatment parameters of extracorporeal high intensity focused ultrasound (HIFU) were analysed in normal and tumor-bearing rabbit liver. HIFU was generated with a 1 MHz transducer and energy was provided by a 7.5 kW power amplifier. In vivo experiments were conducted on 74 New Zealand rabbits. Normal rabbits and rabbits bearing an intrahepatic VX2 tumor were used. In group 1, spatial peak temporal peak (SPTP) intensities ranging from 1470 to 5500 W cm-2 and exposure times from 0.5 to 5 s were tested at a constant depth in the liver; in group 2, the output power was adjusted as a function of the target depth in order to keep constant the focal in situ intensity in the liver; in group 3 (liver tumors), the focal in situ intensity was 1365 W cm-2 in eight rabbits and 500 W cm-2 in nine. In groups 1, 2 and 3, rabbits were sacrificed 48 h after the treatment. Groups 4 and 5 were designated for analysis of the lesion in the normal liver 4 weeks after treatment at 1000 W cm-2 and 3000 W cm-2 SPTP intensities, respectively. In normal rabbits, the lesion volume increased with exposure time at constant intensity; there was a negative correlation between intensity and exposure time (group 1). When the output power was adjusted as a function of the path length, the lesion size was nearly constant (group 2). In VX2 rabbits, tumor destruction rates were significantly higher in rabbits treated at 500 W cm-2 than in rabbits treated at 1365 W cm-2 (p < 0.05; group 3). As in the normal liver, the lesion volume increased with the exposure time at constant intensity. HIFU lesions treated at 1000 w cm-2 (SPTP) healed as thin fibrous scars, and no severe complication occurred (group 4); at 3000 W cm-2 (SPTP), scars were larger and perforation of a neighbouring organ was seen in 7 of 11 rabbits (group 5).
Animals↗
In vivo effects of cavitation alone or in combination with chemotherapy in a peritoneal carcinomatosis in the rat.
Cavitation (volume oscillations and collapse of gas bubbles), as generated by a co-administration of shockwaves (SW) and microbubbles (SWB), induces cytotoxicity in vitro. Moreover, cavitation potentiates the effects of Fluorouracil (FUra) on colon cancer cells. We aimed at reproducing such effects in vivo. A peritoneal carcinomatosis was induced in BDIX rats by intraperitoneal (IP) injection of DHDK12PROb cells. Cavitation was produced by various SW regimens (250 to 750SW) combined with bubbles (air/gelatin emulsion) infused through an IP catheter. In two consecutive experiments, microtumours (day 3 after cell injection) were submitted to various combinations of cavitation and/or Fluorouracil (FUra) and Cisplatinum (CDDP) at either high or low doses. After 30 days, 100% of control animals were dead or presented carcinomatosis with ascites, vs 60% after FUra 5 mg kg dy, day 4 through 8, and 0% after 250 SWB, day 4 and 6 + FUra 5 mg kg dy, day 4 through 8 (P < 0.001); similar differences were found with CDDP. Survival after low dose FUra + SWB was comparable to high dose FUra (25 mg kg dy day through 8) and was improved as compared to low-dose FUra alone. Only a high dose FUra + SWB schedule induced 40% long term (> 150 days) disease-free survival, but also a higher undesirable toxicity (40% toxic deaths within 1 month). It is concluded that cavitation is cytotoxic in vivo and that it potentiates the effects of FUra and CDDP in this animal model.
Animals↗
Prostatic tissue destruction by high-intensity focused ultrasound: experimentation on canine prostate.
High-intensity focused ultrasound (HIFU) has been used transrectally to induce intraprostatic coagulation necrosis lesion in the canine prostate. The device combines a firing system (power amplifier and therapy transducer) and a localization system (ultrasound scanner). Thirty-seven dogs have been treated with ultrasound intensity ranging from 720 W/cm2 to 2300 W/cm2 and shot durations ranging from 1 to 4 seconds. The threshold for focal ultrasonic lesions was determined to be 1000 W/cm2 with a 1-second shot duration. Intraprostatic lesions were obtained without any damage to the rectal wall. These lesions were homogeneous coagulation necroses and progressed first to an inflammatory fibrosis and then to sclerosis with cavity formation. Intraprostatic lesions also occurred with a combination of moderate acoustic intensity (720 W/cm2) and longer shot duration (4 seconds). The temperature reached at the focal point of the transducer was 85 degrees C. The study confirms the possibility of creating irreversible lesions in the prostatic tissue through the rectal wall. The destruction of localized prostatic cancer seems to be possible in the near future using HIFU delivered by the transrectal route.
Animals↗
[Tumor ablation with focalized ultrasound. In vivo experiment with prostatic adenocarcinoma R3327 Mat-Ly-Lu].
Ultrasound can induce tissue lesions by a combination of thermal and mechanical effects related to the tissue absorption of the energy emitted at the focal point of the transducer. The effects of focused ultrasound were studied in vivo in Fisher/Copenhagen hybrid rats bearing Dunning R3327 experimental prostatic carcinoma. The experimental tumour was transplanted by subcutaneous injection into the abdomen of 20 mg of tumour tissue derived from the Mat-Ly-Lu strain. Treatment was performed under general anaesthesia. The animal, maintained in a sarcophage exposing the tumour, was immersed in degassed water ensuring the interface between the tumour and the 1 MHz transducer. The displacements of the transducer were guided by computerised ultrasound screening, allowing irradiation of the entire tumour. The energy was supplied by a 7.5 kW amplifier in the form of series of impulses of variable duration. 77 rats were treated and the tumour growth was compared to that of non-irradiated control rats. Comparative series demonstrated the following results: 1. Immediate tumour destruction was obtained with a very high acoustic intensity (9,000 Watts/cm2) and a brief exposure time. 2. A transient slowing of the tumour growth rate was observed for an acoustic intensity of between 3,500 and 5,500 Watts/cm2. 3. Partial or total necrosis of the tumour was obtained with intensities of between 300 and 2,750 Watts/cm2 and a long exposure time. Total tumour destruction was obtained in 30 of the 49 rats treated under these conditions. 14 animals developed a local recurrence, 9 animals did not develop a local recurrence but developed metastases and 7 animals obtained long-term survival without local recurrence or metastasis. Under certain experimental conditions, focused ultrasound, without any adjuvant treatment, was able to destroy the Dunning R3327 Mat-Ly-Lu strain experimental tumour and, in certain cases, induced complete cure of this experimental cancer.
Animals↗
[Transesophageal echo-Doppler in children: the importance of the exact measurement of the aortic diameter and its variations over time for estimating the aortic output].
The purpose of the study was to evaluate a new non invasive system of hemodynamic monitoring. The aortic systolic, diastolic and mean diameter have been measured with eco-TM and the aortic blood flow with pulsed Doppler, in order to obtain the aortic output. The aortic systolic diameter and the derived aortic output were then compared to the corresponding values obtained with CT. Ten healthy children were asked to be explored with CT under general anaesthesia and an oesophageal probe was positioned. The mean aortic diameter value was 7.18 +/- 0.91 mm. The systolic and diastolic aortic diameter was 7.87 +/- 0.91 mm and 6.65 +/- 1 mm respectively. The aortic systolic diameter measured with CT was 8.2 +/- 0.92 mm. Correlation analysis with aortic systolic diameter with eco TM as the dependent variable and aortic systolic diameter with CT as the independent variable revealed a highly significant correlation (r = 0.95, coefficient of determination 0.90). The mean percentage difference between systolic and diastolic diameter measured with TM eco scan was 15% with maximum variation 22% and minimum of 10% (p less than 0.003). The aortic blood flow calculated from the systolic aortic diameter was 29% higher than that obtained from diastolic aortic diameter. This would suggest that the correct measurement of the aortic diameter has to be considered in the final evaluation of aortic output especially in children in whom the elasticity of the aortic wall represents a major factor in determining fluctuations of aortic diameter.
Aorta↗
Cytotoxic effects of acoustic cavitation on HT-29 cells and a rat peritoneal carcinomatosis in vitro.
Damage to cells and tissues exposed to shock waves (SWs) is thought to be secondary to cavitation phenomena involving the collapse of gas bubbles in a fluid. Using HT-29 cells and DHDK12PROb tumors, we tried to enhance SW-related damage by the simultaneous administration of gas microbubbles. Bubbles resulted from a mixture of air and gelatin (HT-29 cells) or from a carbonated NaCl solution (tumors). HT-29 cells in suspension received either SW (50, 250, or 1000 SWs) alone or in association with bubbles. Trypan blue-negative cells decreased as the number of SWs increased. Exposure to SWs and bubbles resulted in not only an increased but also a delayed mortality as compared to SWs only. One thousand SWs with bubbles induced a complete inhibition of cell growth, with cytoplasmic vacuolae, ruptured membranes, and abnormal nuclear shape and chromatin. Exponential and confluent cells exhibited a similar mortality and growth. DHDK12PROb tumors received either SWs only (50, 100, 250, 500, or 1000 SWs) or SWs with bubbles in vitro. Thymidine incorporation was significantly lower after exposure to SWs with bubbles as compared with controls and SWs only; it was nil by 1000 SWs with bubbles. Histopathological features of tumors exposed to SWs with bubbles included erosion and hemorrhage, disorganized structure, pyknotic nuclei, and cytoplasmic vacuolae. We conclude that cavitation, as produced by a combination of SWs and gas microbubbles, can achieve bioeffects which are relevant to cancer therapy.
Animals↗
Physicochemical determinants of in vitro shock-wave biliary lithotripsy.
Human gallstones were studied by visual inspection, computerized tomographic imaging, and chemical analysis to assess physicochemical characteristics that may determine the outcome of in vitro shock-wave fragmentation. Eighty-five stones (mean diameter: 13.2 +/- 5 mm) were each collected from different patients. Fifty-five (65%) calculi were angular and 30 (35%) round or oval-shaped. Three easily obtained measures were derived from each stone's optimal computerized tomographic image including the mean stone density, a measure corresponding to the standard deviation of the mean stone density value which we termed the stone density distribution index and which may reflect the physicochemical heterogeneity of a given gallstone, as well as the density range. After the administration of 2500 shock waves using an electrohydraulic generator, fragmentation was noted in 68 calculi (80%) and was satisfactory in 27 (32%) (where the largest resulting fragment diameters were all less than or equal to 5 mm). Strong determinants of satisfactory fragmentation on multivariate analysis included a stone diameter of less than or equal to 15 mm, the presence of an angular stone shape, and a stone density distribution index of greater than or equal to 60 Hounsfield units. The other parameters did not independently determine satisfactory fragmentation. Prospective clinical trials are needed to assess whether these findings result in a better prediction of the success of extracorporeal biliary lithotripsy and a broadening of its indications.
Chemical Phenomena↗