Focused low-energy extracorporeal shock waves with distally symmetric polyneuropathy (DSPNP): a pilot study.

BACKGROUND: Incidental observations led to the question whether ESWT could alleviate the still difficult-to-improve symptoms of DSPNP. METHODS: In a pilot study, out of an original 24 patients with DSPNP, 10 patients with diabetes mellitus were excluded because of their inhomogeneous performances. Of the 14 patients remaining, 6 received one sham treatment at the beginning. All 14 patients were then treated with ESWT to the soles of the feet using the Duolith® shock wave generator (Storz Medical) 3 times weekly for 2 weeks. The assessments were carried out before and after the sham treatment, the first ESWT (question: before and after the first ESWT or only after?) and after 2, 4 and 8 weeks. RESULTS: The placebo treatment did not influence pain or paraesthesia. After the 2 weeks of ESWT, intensity decreased from 100% to 23.6%, rising again after 8 weeks to 45.7% of the original state (p < 0.01). The placebo treatment did however have a great effect on walking abilities. The results of ESWT did not become significant until the 8th week. Step length improved by 14.6% (p < 0.001), walking speed by 24.8% (p < 0.001) and time of dual support during the stance phase of the gait declined by 12.2% (p < 0.009). CONCLUSIONS: Despite the small number of cases, it appears that ESWT can alleviate some of the symptoms of DSPNP.

Technical characterization of an ultrasound source for noninvasive thermoablation by high-intensity focused ultrasound.

OBJECTIVE: To develop a generator for high-intensity focused ultrasound (HIFU, a method of delivering ultrasonic energy with resultant heat and tissue destruction to a tight focus at a selected depth within the body), designed for extracorporeal coupling to allow various parenchymal organs to be treated. MATERIAL AND METHODS: The ultrasound generated by a cylindrical piezo-ceramic element is focused at a depth of 10 cm using a parabolic reflector with a diameter of 10 cm. A diagnostic B-mode ultrasonographic transducer is integrated into the source to allow the focus to be located in the target area. The field distribution of the sound pressure was measured in degassed water using a needle hydrophone. An ultrasound-force balance was used to determine the acoustic power. These measurements allowed the spatially averaged sound intensity to be calculated. The morphology and extent of tissue necrosis induced by HIFU was examined on an ex-vivo kidney model. RESULTS: The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (- 6 dB). The spatially maximum averaged sound intensity was 8591 W/cm2 at an electrical power of 400 W. The lesion caused to the ex-vivo kidney at this maximum generator power with a pulse duration of 2 s was a clearly delineated ellipsoidal coagulation necrosis up to 8.8 x 2.3 mm (length x width) and with central liquefied necrosis of 7.9 x 1.9 mm. CONCLUSION: This newly developed ultrasound generator with a focal length of 10 cm can induce clear necrosis in parenchymal tissue. Because of its specific configuration and the available power range of the ultrasound generator, there is potential for therapeutic noninvasive ablation of tissue deep within a patient's body.

Short-time non-enzymatic nitric oxide synthesis from L-arginine and hydrogen peroxide induced by shock waves treatment.

The evidence that nitric oxide (NO) production is possible by a non-enzymatic pathway has already been shown under restrictive experimental conditions. Here we show that NO can non-enzymatically be formed with short-time kinetics (min), by 'bombing' with shock waves a solution containing 1 mM hydrogen peroxide and 10 mM L-arginine. This procedure is widening its medical application with surprisingly positive effects in tissue regeneration and our finding could be one of the first steps for the understanding of the biochemical responsible for these therapeutical effects.

[Control parameters for high-intensity focused ultrasound (HIFU) for tissue ablation in the ex-vivo kidney]. / Steuerparameter des hochenergetischen fokussierten Ultraschalls (HIFU) zur Gewebeablation an der Ex-vivo-Niere.

PURPOSE: Therapeutic application of contactless thermoablation by high-intensity focused ultrasound (HIFU) demands precise physical definition of focal size and determination of control parameters. Our objective was to define the focal expansion of a new ultrasound generator and to evaluate the extent of tissue ablation under variable generator parameters in an ex vivo model. MATERIALS AND METHODS: Axial and transversal distribution of ultrasound intensity in the area of the focal point was calculated by needle hydrophone. The extent of tissue necrosis after focused ultrasound was assessed in an ex vivo porcine kidney model applying generator power up to 400 Watt and pulse duration up to 8 s. RESULTS: The measurement of field distribution revealed a physical focal size of 32 x 4 mm. Sharp demarcation between coagulation necrosis and intact tissue was observed in our tissue model. Lesion size was kept under control by variation of both generator power and impulse duration. At a constant impulse duration of 2 s, generator power of 100 W remained below the threshold doses for induction of a reproducible lesion. An increase in power up to 200 W and 400 W, respectively, induced lesions with diameters up to 11.2 x 3 mm. Constant total energy (generator power x impulse duration) led to a larger lesion size under higher generator power. CONCLUSION: It is possible to induce sharply demarcated, reproducible thermonecrosis, which can be regulated by generator power and impulse duration, by means of a cylindrical piezo element with a paraboloid reflector at a focal distance of 10 cm. The variation of generator power was an especially suitable control parameter for the inducement of a defined lesion size.

Effects of shock waves on the microcirculation in critical limb ischemia (CLI) (8-week study).

Shock waves (SWs) are used to control and decrease pain in several clinical conditions (e.g., painful elbow and shoulder, etc). This clinical effect may be due to cellular stunning of the tissues (particularly nervous components) in the area treated with SW. It may also be the consequence of unknown metabolic actions on tissues, which may include changes in cellular permeability and the liberation of proteins and mediators locally acting on pain and nerve endings. The aim of this study was to evaluate the reduction in pain and the microcirculation improvement induced by SWs treatment in an 8-week study in patients with chronic limb ischemia (CLI). Patients with CLI (15 with rest pain only and 15 with rest pain and limited distal necrosis) were included. The treatment was based on a 30-minute SWs session, three times weekly for 2 weeks. Clinical and microcirculatory evaluation were performed with laser Doppler Po2 and Pco2 measurements. Pain was measured with an analogue scale line. A Minilith SL1 (Storz Medical, Switzerland) litotriptor was used. The parabolic reflector is coupled to the skin with a silicon water cushion. Focal pressure was adjusted between 6 and 70 Mpa in eight steps. The energy flux density was variable from 0.03 to 0.5 mJ/mm2. Focal diameter and distance were defined (depth of target within the patient's foot of about 70 mm). The coded intensity used in this study was between 6 and 8 and the application time was 20 min (at four impulses per second). Twenty-eight of the 30 patients with CLI (15 with rest pain only and 13 with necrosis) completed the study. The treatment was well tolerated. Blood pressure was unchanged after 8 weeks while the increase in laser Doppler flux was significant (p<0.05) (at all measurements after treatment). The ORACLE score at 1 and 8 weeks was decreased (p<0.05). The same trend was observed with the analogue scale line for pain (p<0.05). PO2 increased (p<0.05) and Pco2 decreased (p<0.05). Tibial pressure did not change. All patients observed an increase in their subjective pain-free walking distance. The improvement was still present after 8 weeks. In a separate subset of 37 patients (mean age 60+/-9 years; males) with CLI, a SWs dose-finding evaluation was performed. Flux changes were measured at the dorsum of the foot. Three treatment plans were used: (a) 20-minute SW treatment only once; (b) 20-minute SWs treatment every 2 days for 1 week; (c) 20 minutes every day for 1 week. Treatments were well tolerated. A different increase in flux was observed on the basis of different treatments. Flux variations generally indicated that increased SWs dosage was associated with proportional flux increase. Flux improvement was still present after 4 weeks. SWs treatment in CLI produced changes both in the microcirculation and on pain. These preliminary results are comforting and open new research options to be explored in the near future.

[Extracorporeal shockwave lithotripsy in cholecystolithiasis using a new type of minilithotripter]. / Extrakorporale Stosswellenlithotripsie bei Cholezystolithiasis mittels eines neuartigen Mini-Lithotripters.

BACKGROUND AND OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) of gallstones has until now required fixed, nearly room-sized and expensive equipment. It has become even less cost-effective with an increase in the number of laparoscopic cholecystectomies. The authors have technically modified a mini-lithotripter, used for dissolving salivary stones, for application against gallstones (by changing the energy spectrum and depth of focus). PATIENTS AND METHODS: 125 consecutive patients with solitary gallstone underwent lithotripsy according to a standard protocol (including oral litholysis), 64 of them (average age 42.5 +/- 9.3 years; 44 women, 20 men) by conventional ESWL (with the Modulith), 62 (average age 41.6 +/- 10.1 years; 43 women, 13 men) with a modified mini-lithotripter (Minilith). Clinical and sonographic follow-up took place at 1, 3, 6 and 12 months. Quality of life was documented according to a point score (GIQL), developed specially for patients with gastrointestinal conditions. RESULTS: The mini-lithotripter applied significantly lower voltage and more shock-wave impulses per treatment than the conventional ESWL (p < 0.01), while patient tolerance, measured with a visual analogue scale, was the same. Application of the mini-lithotripter was easier and quicker than with conventional ESWL, namely 31 +/- 8 min vs 41 +/- 12 min (p < 0.01). Frequency of adequate stone fragmentation per patient was the same for both methods, 2.2 +/- 0.5 applications with the mini-lithotripter vs 1.6 +/- 0.3 with conventional ESWL (p < 0.01). There was no significant difference between the methods with regard to improved quality of life (increase of GIQL scale of 16% with the conventional ESWL, 14% with the mini-lithotripter) or freedom from stone at 1 year after lithotripsy (conventional ESWL: 80%, mini-lithotripter: 82%). Colics recurred in 15 of 64 patients receiving conventional ESWL, and in 13 of 61 in the mini-lithotripter group (difference not significant). There were no other complications. CONCLUSION: The cheaper mini-lithotripter, costing only a third of the conventional ESWL, is equally effective in the dissolution of gallstones.

Shock waves (SW) noninvasive extracorporeal thrombolysis treatment (NISWT).

A group of 24 patients were considered for noninvasive shock waves thrombolysis (NISWT). Of these, 15 patients gave their informed consent. NISWT was attempted in eight patients (while seven patients were randomized for follow-up only). NISWT was possible in six of seven patients. In one patient randomized for NISWT, local inguinal scarring, due to previous surgery, made impossible the visualization of the femoral vein, and therefore focusing of shock waves (SWs). No side effects were reported in the days after SWs administration during the 4-month follow-up. In patients treated with NISWT it was possible to observe just after the SWs session the presence of echolucent "acoustic holes" and flow (by color and power Doppler) within the "holes." All "echolucent holes" produced at the first session were still present at 4 months, and color flow imaging also detected new flow channels in echogenic areas of thrombi previously not visible. In one patient thrombolysis was achieved after the first treatment, but at 3 and 4 months the thrombus was completely avascular. In conclusion, thrombolysis using SWs was obtained in selected cases and it was still persisting at 4 months in six of the seven treated patients. NISWT appears feasible and promising. These results should be confirmed by larger, prospective trials.

Shock waves in vascular diseases: an in-vitro study.

UNLABELLED: Three human aortic specimens were used for this in-vitro study on the effects of shock waves on the arterial wall. Specimen one was from a normal (for age) healthy aorta. The full abdominal length was used (including mesenteric and renal arteries and the aortoiliac bifurcation), divided into six pieces (3 cm). The pieces were placed and fixed into degassed water. Shock waves (SW) were focused onto the aortic wall by means of a B-mode ultrasound imager. An SW generator (Minilith SL1, Storz Medical AG, Kreuzlingen, Switzerland) was used for setting of energy flux density between 0.03 and 0.5 mJ/mm2. The six aortic pieces (excluding piece 1, placed in water and left untreated as control) were treated with SW at increasing energy levels. A second aortic specimen of a man with arteriosclerotic plaques was also used and the experiment repeated at energy levels 1, 5, and 8. Another specimen of normal thoracic aorta was exposed at energy levels 1 and 8 only. Energy levels delivered onto the aortic walls were selected from theoretically destructive levels to minimal levels known not to alter vascular tissues. High-resolution ultrasounds of the aortic segments were performed with a 10 MHz high-resolution, broad-band (ATL 3000, USA) probe in water before and after SW application to detect structural changes in the wall after SW. Histology was performed with a standard hematoxylin-eosin staining. RESULTS: The aortic pieces did not show macroscopic damages at visual examination, and at the ultrasound examination no visible changes were observed even at higher levels of SW energy. Also no effects were seen by histology. In conclusion, no damaging effects were observed, visually, by ultrasound, or by histology. At these energy levels SW appear to be safe and do not produce any damage to the aortic wall. Therefore, SW could be considered a safe, nondamaging procedure for potential treatment (ie, thrombolysis) in which vessel walls could be involved. Theoretically it is possible that functional changes could be observed in vivo including cell permeability modifications and other alterations (including changes in the potential of the cells in SW fields to modify themselves and to divide). At the energy levels described in this study SW could, theoretically be, safely used for vascular applications (ie, treating venous and arterial thrombi or in arterial plaques modification) without altering major, structural, arterial wall characteristics. Lesions or alterations that have a different density from the normal wall (thrombi or plaques) could be differently sensitive to the same dosage of SW. These differences in acoustic impedance characteristics could be used for potential treatments with SW without damaging the arterial wall.

Shock wave treatment of salivary duct stones: substantial progress with a minilithotripter.

Extracorporeal shock wave lithotripsy has recently been introduced as the first non-operative treatment alternative for patients with sialolithiasis. Using conventional multipurpose lithotripters, however, successful treatment was achieved in only 36%-53% of patients. Therefore we developed an miniaturized lithotripter meeting the special requirements for extracorporeal shock wave treatment in the head and neck region. During a 1-year prospective trial clinical efficacy and safety were compared in 40 patients treated with a conventional electromagnetic lithotripter (group A) to 33 patients treated with the newly developed, miniaturized device (group B). The groups did not differ statistically regarding stone size or number or the proportion of stones located in the submandibular or parotid gland. Successful stone targeting, a prerequisite for shock wave treatment, was achieved by means of in-line ultrasonography in 30 of the 40 patients in group A and in 29 of 33 patients of group B. The number of shock wave impulses administered per session and the maximum shock wave intensities did not differ in the two groups. Significantly more frequent treatments with a longer mean duration of each session were required in group A (2.4 +/- 1.0 treatments, 47 +/- 11 min) than in group B (1.9 +/- 0.7 treatments, 28 +/- 9 min; P < 0.05). After a 3 month follow-up significantly more patients were free of stones in group B (22/33) than in group A (16/40; P < 0.05). Correspondingly, the number of patients free of complaints was significantly higher in group B (27/33) than in group A (22/40; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental basis of shockwave-induced renal trauma in the model of the canine kidney.

Using the new electromagnetic shockwave source of the Modulith SL 20 shockwave-induced renal trauma was evaluated by acute and chronic studies in the the canine kidney model. In a further study the electromagnetic shockwave source of the Lithostar Plus Overhead module was tested. Overall, 92 kidneys were exposed to shock waves coupled either by water bath (Modulith lab type) or by water cushion (Modulith prototype, Lithostar Overhead) under ultrasound localization. The generator voltage ranged between 11 and 21 kV, the number of impulses between 25 and 2500. After application of 1500/2500 shocks the extent of the renal lesion depended strictly on the applied generator voltage and was classified into 4 grades: Grade 0, no macroscopic trauma detectable (at 11-12 kV); grade 1, petechial medullary bleeding (at 13 kV); grade 2, cortical hematoma (at 14-16 kV); and grade 3, perirenal hematoma (17-20 kV). Whereas at low and medium energy levels the number of shocks played only a minor role, at maximal generator voltage (20 kV) even 25 impulses induced a grade 2 and 600 shocks a grade 3 lesion, emphasizing the importance of shockwave limitation in the upper energy range. In shockwave-induced renal trauma a vascular lesion was predominant and cellular necrosis was secondary. Coupling with a water cushion resulted in a 15%-20% decrease in the disintegrative and traumatic effect, which was compensated for by increasing the generator voltage by 2 kV. Long-term studies showed complete restitution following grade 1 and 2 trauma, whereas after a grade 3 lesion a small segmental and capsular fibrosis without hyperplasia of the juxtaglomerular apparatus was observed. Based on the characteristic ultrasound pattern found in the first study, the threshold for induction of grade 1 lesion was investigated. With both lithotripters a wide range for induction of a grade 1 lesion (Modulith 234-411, Lithostar Plus 220-740) and also a significant overlapping with grade 0 and 2 lesions was seen at low energy settings (levels 2-4). In contrast, the range of shocks (Modulith 96-150, Lithostar Plus 90-142) and overlapping was minimal when high energy was used (levels 7-9). Finally, the disintegration-trauma coefficient combining the results obtained in a standard stone model with those of the canine kidney model was introduced.

A new pressure wave generator for extracorporeal lithotripsy.

A new pressure wave generator has been designed for the Storz Modulith extracorporeal lithotripter. It consists of an electromagnetic cylindrical pressure wave source and a focusing parabolic reflector. Focus size has been designed using electro-acoustic puls forming network (EA-PFN) techniques. Schlieren photographs of the pressure wave are shown. Pressure in the focus is given as a function of PFN charging voltage.

Biological effects of shock waves: kidney haemorrhage by shock waves in dogs--administration rate dependence.

The effect of shock waves on normal canine kidneys was examined in two groups of dogs whose right kidneys were exposed to 3000 shock waves generated with 20 kV and 40 nF in a Dornier HM II lithotripter. The groups differed only in the rate of shock wave administration which was 100 and 1 per second, respectively. Autopsy was performed 24 to 30 h later. Macroscopically and histologically, significantly more haemorrhages occurred in the kidney parenchyma if shock waves were administered at a rate of 100 waves per second. Haemorrhages were diffuse, the outer medulla was most heavily affected. The results show that kidney damage is dependent on the rate of shock wave administration. They argue against a direct shock wave effect and favor cavitation as the mechanism of shock wave damage although thermal effects cannot be excluded.