Development of a novel shock wave catheter ablation system-A validation study in pigs in vivo.

Aims: Although the radiofrequency catheter ablation (RFCA) is widely used for the treatment of tachyarrhythmias, it has three fundamental weaknesses as a thermal ablation system, including a limited lesion depth, myoendocardial injury linking to thromboembolism, and prolonged inflammation followed by subsequent recurrences. In order to overcome these limitations, we have been developing a shock wave (SW) catheter ablation (SWCA) system as a novel non-thermal therapy. In the present study, we validated our new SWCA system with increased SW intensity. Methods and results: In a total of 36 pigs, we applied our new SWCA to ventricular muscle in vivo for the following protocols. (i) Epicardial approach (n = 17): The lesion depth achieved by the SWCA from the epicardium was examined. High intensity SW achieved 5.2 ± 0.9 mm lesions (35 applications), where there was a strong correlation between SW intensity and lesion depth (R = 0.80, P < 0.001, 54 applications). (ii) Endocardial approach (n = 6): The extent of endocardial injury with the two energy sources was examined by electron microscopy (8 applications each). Shock wave catheter ablation markedly reduced myoendothelial injury compared with RFCA (4.3 ± 1.2 vs. 79.6 ± 4.8%, P < 0.01). The electrophysiological effects on the SW lesions were also confirmed using three-dimensional mapping system. (iii) Time-course study (n = 6 each): The healing process after ablation therapy was examined. We found transient inflammatory responses and accelerated reparative process with preserved blood flow in the SWCA group. Conclusion: These results indicate that our SWCA system is characterized, as compared with RFCA, by deeper lesion depth, markedly less myoendocardial injury and accelerated tissue repair process.

Experimental application of pulsed laser-induced water jet for endoscopic submucosal dissection: mechanical investigation and preliminary experiment in swine.

BACKGROUND AND AIM: A current drawback of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors is the lack of instruments that can safely assist with this procedure. We have developed a pulsed jet device that can be incorporated into a gastrointestinal endoscope. Here, we investigated the mechanical profile of the pulsed jet device and demonstrated the usefulness of this instrument in esophageal ESD in swine. METHODS: The device comprises a 5-Fr catheter, a 14-mm long stainless steel tube for generating the pulsed water jet, a nozzle and an optical quartz fiber. The pulsed water jet was generated at pulse rates of 3 Hz by irradiating the physiological saline (4°C) within the stainless steel tube with an holmium-doped yttrium-aluminum-garnet (Ho:YAG) laser at 1.1 J/pulse. Mechanical characteristics were evaluated using a force meter. The device was used only for the part of submucosal dissection in the swine ESD model. Tissues removed using the pulsed jet device and a conventional electrocautery device, and the esophagus, were histologically examined to assess thermal damage. RESULTS: The peak impact force was observed at a stand-off distance of 40 mm (1.1 J/pulse). ESD using the pulsed jet device was successful, as the tissue specimens showed precise dissection of the submucosal layer. The extent of thermal injury was significantly lower in the dissected bed using the pulsed jet device. CONCLUSION: The results showed that the present endoscopic pulsed jet system is a useful alternative for a safe ESD with minimum tissue injury.

Pulsed laser-induced liquid jet for skull base tumor removal with vascular preservation through the transsphenoidal approach: a clinical investigation.

BACKGROUND: The transsphenoidal approach has recently been used to treat complex lesions beyond the sella turcica, but the difficulties of dealing with small vessels, deep and narrow space, and working angle may limit the procedures. To overcome these problems, we have developed a pulsed laser-induced liquid jet (LILJ) system to dissect tumor tissue with preservation of fine blood vessels within deep and narrow working spaces and evaluated its utility and safety. METHODS: The LILJ system was applied to 14 consecutive patients with uncharacteristically complex skull base tumor treated through the extended transsphenoidal approach. This system consists of a bayonet-shaped catheter incorporating a jet generator formed of stainless tube (external diameter 1.10 mm, internal diameter 0.78 mm), which was surrounded by a coaxial polytetrafluoroethylene 14-G equivalent suction tube to be able to incorporate into the confined working spaces. Minor modifications could be fitted for the catheter (15 to 18 cm length, straight or side flexion tip), and total weight was around 7 g. FINDINGS: Precise dissection and mass reduction of the tumor were obtained in all cases except one recurrent case of chordoma with significant fibrosis due to radiation. Both small arteries and veins were preserved, allowing subsequent microsurgical devascularization. Intraoperative blood loss was minimal, and tumor removal rate was satisfactory after the introduction of the system. No complication was related to use of the LILJ system. CONCLUSION: Although comparison between conventional surgical instruments is mandatory in the future, the present study suggests that the LILJ system can achieve safe and optimum removal of complex skull base tumor. Potential application for minimally invasive endoscopic system, as well as potentials for changing the design of the catheter in according to preference of surgeon with low cost, may give advantages over conventional surgical instruments.

Development of a Shock-Wave Catheter Ablation System for Ventricular Tachyarrhythmias: Validation Study in Pigs In Vivo.

Background Although radiofrequency catheter ablation is the current state-of-the-art treatment for ventricular tachyarrhythmias, it has limited success for several reasons, including insufficient lesion depth, prolonged inflammation with subsequent recurrence, and thromboembolisms due to myoendocardial thermal injury. Because shock waves can be applied to deep lesions without heat, we have been developing a shock-wave catheter ablation ( SWCA ) system to overcome these fundamental limitations of radiofrequency catheter ablation. In this study, we evaluated the efficacy and safety of our SWCA system for clinical application to treat ventricular tachyarrhythmia. Methods and Results In 33 pigs, we examined SWCA in vivo for the following 4 protocols. First, in an epicardial substrate model (n=8), endocardial SWCA significantly decreased the sensing threshold (pre- versus postablation: 11.4±3.8 versus 6.8±3.6 mV ; P<0.05) and increased the pacing threshold (pre- versus postablation: 1.6±0.8 versus 2.0±1.1 V; P<0.05), whereas endocardial radiofrequency catheter ablation failed to do so. Second, in a myocardial infarction model (n=3), epicardial SWCA of the border zone of the infarcted lesion was as effective as ablation of the normal myocardium. Third, in a coronary artery application model (n=10), direct application of shock waves to the epicardial coronary arteries caused no adverse effects in either the acute or chronic phase. Fourth, with an epicardial approach (n=8), we found that 90 shots per site provided an ideal therapeutic condition to create deep lesions with less superficial damage. Conclusions These results indicate that our new SWCA system is effective and safe for treatment of ventricular tachyarrhythmias with deep arrhythmogenic substrates.

Shock wave-induced brain injury in rat: novel traumatic brain injury animal model.

BACKGROUND: In blast wave injury and high-energy traumatic brain injury, shock waves (SW) play an important role along with cavitation phenomena. However, due to lack of reliable and reproducible technical approaches, extensive study of this type of injury has not yet been reported. The present study aims to develop reliable SW-induced brain injury model by focusing micro-explosion generated SW in the rat brain. METHODS: Adult male rats were exposed to single SW focusing created by detonation of microgram order of silver azide crystals with laser irradiation at a focal point of a truncated ellipsoidal cavity of20 mm minor diameter and the major to minor diameter ratio of 1.41 after craniotomy. The pressure profile was recorded using polyvinylidene fluoride needle hydrophone. Animals were divided into three groups according to the given overpressure: Group I: Control, Group II: 12.5 +/- 2.5 MPa (high pressure), and Group III: 1.0 +/- 0.2 MPa (low pressure). Histological changes were evaluated over time by hematoxylin-eosin staining. FINDINGS: Group II SW injuries resulted in contusional hemorrhage in reproducible manner. Group III exposure resulted in spindle-shaped changes of neurons and elongation of nucleus without marked neuronal injury. CONCLUSIONS: The use of SW loading by micro-explosion is useful to provide a reliable and reproducible SW-induced brain injury model in rats.

[Clinical application of pulsed laser-induced liquid jet: preliminary report in glioma surgery].

PURPOSE: Both maximum resection of tumor and preservation of fine vessels are conflicting aims, but important factors to improve outcome in glioma surgery. Water jet dissection has been reported to dissect tissue while ensuring preservation of fine vessels. However, it was difficult to apply conventional water jet device in microsurgery due to the use of high pressure and continuous water a flow. To overcome these issues, we have developed pulsed holmium: yttrium-aluminum-garnet (YAG) laser-induced liquid jet (LILJ) for microsugical use and applied it in glioma surgery. METHODS: LILJ was generated by irradiating pulsed Ho: YAG laser (3 Hz, pulse laser energy 233-300 mJ/pulse) within a stainless tube (outer diameter (OD): 1.26 mm inner diameter (ID): 0.90 mm) filled with cold (4 degrees C) lactated Ringer's solution. The laser beam was conducted through optical quartz fiber (core diameter: 400 microm). The jet generated was ejected from a stainless nozzle (OD: 1.06 mm, ID: 0.70 mm). To avoid splash and air bubbles within the surgical field, the nozzle was placed inside a stainless suction tube (OD: 3.06 mm, ID: 2.64 mm). LILJ was ejected randomly toward blood vessels and tissue simultaneously after removal of arachnoid membrane by microsurgical technique, and the quality of the dissection and the visual field were evaluated in 4 patients with supratentorial glioma. RESULTS: Restoration of small arteries (diameter: 100 to 200 microns) was accomplished. There was no significant occurrence of splash or air bubbles under the microscopic view. CONCLUSION: Present results showed that the pulsed LILJ system may safely be used for microsurgical procedures, and may be useful for glioma resection where preservation of fine vessels is required.

Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosis mediated by a caspase-dependent pathway.

OBJECT: Shock waves have been experimentally applied to various neurosurgical treatments including fragmentation of cerebral emboli, perforation of cyst walls or tissue, and delivery of drugs into cells. Nevertheless, the application of shock waves to clinical neurosurgery remains challenging because the threshold for shock wave-induced brain injury has not been determined. The authors investigated the pressure-dependent effect of shock waves on histological changes of rat brain, focusing especially on apoptosis. METHODS: Adult male rats were exposed to a single shot of shock waves (produced by silver azide explosion) at overpressures of 1 or 10 MPa after craniotomy. Histological changes were evaluated sequentially by H & E staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The expression of active caspase-3 and the effect of the nonselective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were examined to evaluate the contribution of a caspase-dependent pathway to shock wave-induced brain injury. High-overpressure (> 10 MPa) shock wave exposure resulted in contusional hemorrhage associated with a significant increase in TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave application. Low-overpressure (1 MPa) shock wave exposure resulted in spindle-shaped changes in neurons and elongation of nuclei without marked neuronal injury. The administration of Z-VAD-FMK significantly reduced the number of TUNEL-positive cells observed 24 hours after high-overpressure shock wave exposure (p < 0.01). A significant increase in the cytosolic expression of active caspase-3 was evident 24 hours after high-overpressure shock wave application; this increase was prevented by Z-VAD-FMK administration. Double immunofluorescence staining showed that TUNEL-positive cells were exclusively neurons. CONCLUSIONS: The threshold for shock wave-induced brain injury is speculated to be under 1 MPa, a level that is lower than the threshold for other organs. High-overpressure shock wave exposure results in brain injury, including neuronal apoptosis mediated by a caspase-dependent pathway. This is the first report in which the pressure-dependent effect of shock wave on the histological characteristics of brain tissue is demonstrated.

Bead-like passage of chloride ions through ClC chloride channels.

The ClC chloride channels control the ionic composition of the cytoplasm and the volume of cells, and regulate electrical excitability. Recently, it has been proposed that prokaryotic ClC channels are H+-Cl- exchange transporter. Although X-ray and molecular dynamics (MD) studies of bacterial ClC channels have investigated the filter open-close and ion permeation mechanism of channels, details have remained unclear. We performed MD simulations of ClC channels involving H+, Na+, K+, or H3O+ in the intracellular region to elucidate the open-close mechanism, and to clarify the role of H+ ion an H+-Cl- exchange transporter. Our simulations revealed that H+ and Na+ caused channel opening and the passage of Cl- ions. Na+ induced a bead-like string of Cl- -Na+-Cl--Na+-Cl- ions to form and permeate through ClC channels to the intracellular side with the widening of the channel pathway.

[Intraoperative brain surface blood flow monitoring using IRIS V thermographic imaging system in patients with Moyamoya disease].

Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving CBF. But little is known about the changes of intraoperative cerebral hemodynamics and its effect on postoperative neurological status including symptomatic cerebral hyperperfusion. To address this issue, we applied a novel infrared camera system (IRIS-V thermographic system) for real-time, visual monitoring of surface CBF during surgery in patients with moyamoya disease. Seven patients (8 sides, male:female= 3:4, 7-62 years old) with moyamoya disease were included in the study. After STA-MCA anastomosis, STA were occluded transiently and recanalized, and whole sequence was recorded by IRIS-V system. Correlation between clinical, radiological findings and infrared imaging were investigated. Patency of bypass was confirmed by this camera during surgery in all cases. The intraoperative imaging patterns were divided into two groups. Group A: Change of brain surface color (++) (3 cases). Group B: Change of brain surface color (-) (4 cases). Transient symptomatic hyperperfusion occurred in all patients in Group A, whereas all patients in Group B showed non-symptomatic transient focal hyperperfusion on SPECT. No patient suffered permanent neurological deterioration compared to preoperative status. Characteristic pattern of the intraoperative cerebral hemodynamics as delineated by IRIS-V could be the optimal predictor for postoperative transient symptomatic hyperperfusion after direct bypass in patients with moyamoya disease.

Compact monochromatic flash x-ray generator utilizing a disk-cathode molybdenum tube.

The high-voltage condensers in a polarity-inversion two-stage Marx surge generator are charged from -50 to -70 kV by a power supply, and the electric charges in the condensers are discharged to an x-ray tube after closing gap switches in the surge generator with a trigger device. The x-ray tube is a demountable diode, and the turbo molecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Clean molybdenum Kalpha lines are produced using a 20 microm-thick zirconium filter, since the tube utilizes a disk cathode and a rod target, and bremsstrahlung rays are not emitted in the opposite direction to that of electron acceleration. At a charging voltage of -70 kV, the instantaneous tube voltage and current were 120 kV and 1.0 kA, respectively. The x-ray pulse widths were approximately 70 ns, and the generator produced instantaneous number of Kalpha photons was approximately 3 x 10(7) photons/cm2 per pulse at 0.5 m from the source of 3.0 mm in diameter.

A proposed parent vessel geometry-based categorization of saccular intracranial aneurysms: computational flow dynamics analysis of the risk factors for lesion rupture.

OBJECT: The authors created a simple, broadly applicable classification of saccular intracranial aneurysms into three categories: sidewall (SW), sidewall with branching vessel (SWBV), and endwall (EW) according to the angiographically documented patterns of their parent arteries. Using computational flow dynamics analysis (CFDA) of simple models representing the three aneurysm categories, the authors analyzed geometry-related risk factors such as neck width, parent artery curvature, and angulation of the branching vessels. METHODS: The authors performed CFDAs of 68 aneurysmal geometric formations documented on angiograms that had been obtained in patients with 45 ruptured and 23 unruptured lesions. In successfully studied CFDA cases, the wall shear stress, blood velocity, and pressure maps were examined and correlated with aneurysm rupture points. Statistical analysis of the cases involving aneurysm rupture revealed a statistically significant correlation between aneurysm depth and both neck size (p < 0.0001) and caliber of draining arteries (p < 0.0001). Wider-necked aneurysms or those with wider-caliber draining vessels were found to be high-flow lesions that tended to rupture at larger sizes. Smaller-necked aneurysms or those with smaller-caliber draining vessels were found to be low-flow lesions that tended to rupture at smaller sizes. The incidence of ruptured aneurysms with an aspect ratio (depth/neck) exceeding 1.6 was 100% in the SW and SWBV categories, whereas the incidence was only 28.75% for the EW aneurysms. CONCLUSIONS: The application of standardized categories enables the comparison of results for various aneurysms' geometric formations, thus assisting in their management. The proposed classification system may provide a promising means of understanding the natural history of saccular intracranial aneurysms.

Development of a novel shock wave catheter ablation system--the first feasibility study in pigs.

INTRODUCTION: Radio-frequency catheter ablation (RFCA) using Joule heat has two fundamental weaknesses: the limited depth of treatment and the risk of thrombus formation. In contrast, focused shock wave (SW) therapy could damage tissues at arbitrary depths without heat generation. Thus, we aimed to develop a SW catheter ablation (SWCA) system that could compensate for the weaknesses of RFCA therapy. METHODS AND RESULTS: We developed a SWCA system where the SW generated by a Q-switched Holmium: yttrium aluminum garnet (YAG) laser beam was reflected by a reflector attached to 14-Fr catheter tip and then was converged onto the focus. We examined the feasibility of our system on pigs in vivo. When applied using the epicardial approach, the SWCA caused persistent spheroidal lesions with mild superficial injury than the RFCA. The lesions were created to a depth based on the focal length (2.0 mm) [2.36 ± 0.45 (SD) mm immediately after procedure, n = 16]. When applied to the atrioventricular (AV) node using the endocardial approach, the SWCA caused junctional escape rhythms in 2 pigs and AV block in 12 pigs (complete AV block in 9) in acute phase (n = 14). Nine of the 14 pigs survived with pacemakers for the long-term study, and the AV block persisted for 12.6 ± 3.9 (SD) days in all surviving pigs. Histological examination showed AV nodal cell body atrophy in the acute phase and fibrotic lesions in the chronic phase. Importantly, no acute or chronic fatal complications were noted. CONCLUSIONS: Our novel SWCA system could be a promising modality as a non-thermal ablation method to compensate for the weaknesses of RFCA therapy. However, further research and development will be necessary as the current prototype still exhibited the presence of micro-thrombus formation in the animal studies.

Ca2+ binding sites in calmodulin and troponin C alter interhelical angle movements.

Molecular dynamics analyses were performed to examine conformational changes in the C-domain of calmodulin and the N-domain of troponin C induced by binding of Ca(2+) ions. Analyses of conformational changes in calmodulin and troponin C indicated that the shortening of the distance between Ca(2+) ions and Ca(2+) binding sites of helices caused widening of the distance between Ca(2+) binding sites of helices on opposite sides, while the hydrophobic side chains in the center of helices hardly moved due to their steric hindrance. This conformational change acts as the clothespin mechanism.

Hemodynamic analysis of an adult vein of Galen aneurysm malformation by use of 3D image-based computational fluid dynamics.

We applied computational fluid dynamic (CFD) analysis on the numerical grid of a 3D rotational digital subtraction angiogram obtained in a 22-year-old male patient, with an accidentally discovered vein of Galen malformation associated with single feeder aneurysm, to understand the flow pattern through the two aneurysms and improve our general understanding of hemodynamic characteristics of this variety of fusiform aneurysm. This technical note provides a good example of the application of CFD to 3D digital subtraction angiography for studying the flow pattern in patients with cerebrovascular disease.

Computational replicas: anatomic reconstructions of cerebral vessels as volume numerical grids at three-dimensional angiography.

BACKGROUND AND PURPOSE: We present a relatively simple approach that physicians can use to reconstruct cerebral vessels as 3D numerical grids or computational replicas. The method accurately duplicates their geometry to provide computer simulations of their blood flow. METHODS: Initial images were obtained by using any medical imaging technique, such as MR angiography, CT angiography, or 3D digital subtraction angiography. The data were collected in DICOM format and converted by a DICOM reader into a 3D gray-scale raster image. The image was then processed by using commercial visualization and mesh generation software, which allowed extraction of the luminal surface of the blood vessel (by using the isosurfacing technique). The subsequent final output was an unstructured tetrahedral grid that can be directly used for detailed analysis of cerebral vascular geometry for patient-specific simulations of blood flow. RESULTS: Four examples of grid reconstruction and blood flow simulation for patients with ruptured aneurysms were validated with angiographic and operative findings. The ruptured areas were correlated with areas of high fluid-induced wall-shear stress. CONCLUSION: This approach promises to be a practical tool for planning treatment and follow-up of patients after neurosurgical or endovascular interventions with 3D angiography. The proposed commercial packages or conceptually similar ones seem to be relatively simple and suitable for direct use by neurosurgeons or neuroradiologists.

Computational simulation of therapeutic parent artery occlusion to treat giant vertebrobasilar aneurysm.

We applied computational fluid dynamics (CFD) analysis to assess 3D digital subtraction angiography findings in a patient with a giant vertebrobasilar aneurysm to simulate and compare the consequences of left and right vertebral artery occlusion. The balloon occlusion test suggested that occlusion of the right vertebral artery is the better way to treat this patient's aneurysm from the point of view of aneurysmal thrombosis and isolation from the circulation. The computer simulation supported this conclusion, at the same time indicating that from the point of view of pressure distribution on the wall of the aneurysm, the right vertebral occlusion may be also accompanied by an undesirable effect. A high-pressure area on the aneurysm wall in systole was revealed. This high pressure potentially could lead to subsequent aneurysmal growth, which indeed occurred, as was revealed by a follow-up examination 6 months later. This study is a good example of possible future applications of CFD in patients with cerebrovascular disease before therapeutic intervention.

Demonstration of enhanced K-edge angiography using a cerium target x-ray generator.

The cerium target x-ray generator is useful in order to perform enhanced K-edge angiography using a cone beam because K-series characteristic x rays from the cerium target are absorbed effectively by iodine-based contrast mediums. The x-ray generator consists of a main controller, a unit with a Cockcroft-Walton circuit and a fixed anode x-ray tube, and a personal computer. The tube is a glass-enclosed diode with a cerium target and a 0.5-mm-thick beryllium window. The maximum tube voltage and current were 65 kV and 0.4 mA, respectively, and the focal-spot sizes were 1.0 x 1.3 mm. Cerium Kalpha lines were left using a barium sulfate filter, and the x-ray intensity was 0.48 microC/kg at 1.0 m from the source with a tube voltage of 60 kV, a current of 0.40 mA, and an exposure time of 1.0 s. Angiography was performed with a computed radiography system using iodine-based microspheres. In coronary angiography of nonliving animals, we observed fine blood vessels of approximately 100 microm with high contrasts.

Application of shock waves as a treatment modality in the vicinity of the brain and skull.

OBJECT: Shock waves have not previously been used as a treatment modality for lesions in the brain and skull because of the lack of a suitable shock wave source and concerns about safety. Therefore, the authors have performed experiments aimed at developing both a new, compact shock wave generator with a holmium:yttrium-aluminum-garnet (Ho:YAG) laser and a safe method for exposing the surface of the brain to these shock waves. METHODS: Twenty male Sprague-Dawley rats were used in this study. In 10 rats, a single shock wave was delivered directly to the brain, whereas the protective effect of inserting a 0.7-mm-thick expanded polytetrafluoroethylene (ePTFE) dural substitute between the dura mater and skull before applying the shock wave was investigated in the other 10 rats. Visualizations on shadowgraphy along with pressure measurements were obtained to confirm that the shock wave generator was capable of conveying waves in a limited volume without harmful effects to the target. The attenuation rates of shock waves administered through a 0.7-mm-thick ePTFE dural substitute and a surgical cottonoid were measured to determine which of these materials was suitable for avoiding propagation of the shock wave beyond the target. CONCLUSIONS: Using the shock wave generator with the Ho:YAG laser, a localized shock wave (with a maximum overpressure of 50 bar) can be generated from a small device (external diameter 15 mm, weight 20 g). The placement of a 0.7-mm-thick ePTFE dural substitute over the dura mater reduces the overpressure of the shock wave by 96% and eliminates damage to surrounding tissue in the rat brain. These findings indicate possibilities for applying shock waves in various neurosurgical treatments such as cranioplasty, local drug delivery, embolysis, and pain management.

Pulsed holmium:yttrium-aluminum-garnet laser-induced liquid jet as a novel dissection device in neuroendoscopic surgery.

OBJECT: A pressure-driven continuous jet of water has been reported to be a feasible tool for neuroendoscopic dissection owing to its superiority at selective tissue dissection in the absence of thermal effects. With respect to a safe, accurate dissection, however, continuous water flow may not be suitable for intraventricular use. The authors performed experiments aimed at solving problems associated with continuous flow by using a pulsed holmium:yttrium-aluminum-garnet (Ho:YAG) laser-induced liquid jet (LILJ). They present this candidate neuroendoscopic LILJ dissection system, having examined its mechanical characteristics and evaluated its controllability both in a tissue phantom and in a rabbit cadaveric ventricle wall. METHODS: The LILJ generator was incorporated into the tip of a No. 4 French catheter so that the LILJ could be delivered via a neuroendoscope. Briefly, the LILJ was generated by irradiating an internally supplied column of physiological saline with a pulsed Ho:YAG laser (pulse duration time 350 microsec; laser energy 250-700 mJ/pulse) within a No. 4 French catheter (internal diameter 1 mm) and ejecting it from a metal nozzle (internal diameter 100 microm). The Ho:YAG laser energy pulses were conveyed by an optical fiber (core diameter 400 microm) at 3 Hz, whereas physiological saline (4 degrees C) was supplied at a rate of 40 ml/hour. The mechanical characteristics of the pulsed LILJ were investigated using high-speed photography and pressure measurements; thermal effects and controllability were analyzed using an artificial tissue model (10% gelatin of 1 mm thickness). Finally, the ventricle wall of a rabbit cadaver was dissected using the LILJ. Jet pressure increased in accordance with laser energy from 0.1 to 2 bar; this translated into a penetration depth of 0.08 to 0.9 mm per shot in the ventricle wall of the rabbit cadaver. The gelatin phantom could be cut into the desired shape without significant thermal effects and in the intended manner, with a good surgical view. CONCLUSIONS: The present results show that the pulsed LILJ has the potential to become a safe and reliable dissecting method for endoscopic procedures.

Laser plasma jet driven microparticles for DNA/drug delivery.

This paper describes a microparticle delivery device that generates a plasma jet through laser ablation of a thin metal foil and uses the jet to accomplish particle delivery into soft living targets for transferring biological agents. Pure gold microparticles of 1 µm size were coated with a plasmid DNA, pIG121Hm, and were deposited as a thin layer on one surface of an aluminum foil. The laser (Nd:YAG, 1064 nm wavelength) ablation of the foil generated a plasma jet that carried the DNA coated particles into the living onion cells. The particles could effectively penetrate the target cells and disseminate the DNA, effecting the transfection of the cells. Generation of the plasma jet on laser ablation of the foil and its role as a carrier of microparticles was visualized using a high-speed video camera, Shimadzu HPV-1, at a frame rate of 500 kfps (2 µs interframe interval) in a shadowgraph optical set-up. The particle speed could be measured from the visualized images, which was about 770 m/s initially, increased to a magnitude of 1320 m/s, and after a quasi-steady state over a distance of 10 mm with an average magnitude of 1100 m/s, started declining, which typically is the trend of a high-speed, pulsed, compressible jet. Aluminum launch pad (for the particles) was used in the present study to make the procedure cost-effective, whereas the guided, biocompatible launch pads made of gold, silver or titanium can be used in the device during the actual clinical operations. The particle delivery device has a potential to have a miniature form and can be an effective, hand-held drug/DNA delivery device for biological applications.