Plant-based model for the visual evaluation of electroporated area after irreversible electroporation and its comparison to in-vivo animal data.

Electroporation (EP) is widely used in medicine, such as cancer treatment, in form of electrochemotherapy or irreversible electroporation (IRE). For EP device testing, living cells or tissue inside a living organism (including animals) are needed. Plant-based models seem to be a promising alternative to substitute animal models in research. The aim of this study is to find a suitable plant-based model for visual evaluation of IRE, and to compare the geometry of electroporated areas with in-vivo animal data.For this purpose, a variety of fruit and vegetables were selected and visually evaluated after 0/1/2/4/6/8/12/16/24 h post-EP. Apple and potato were found to be suitable models as they enabled a visual evaluation of the electroporated area. For these models, the size of the electroporated area was determined after 0/1/2/4/6/8/12/16/24 h. For apples, a well-defined electroporated area was visual within two hours, while in potatoes it reached a plateau after eight hours only. The electroporated area of apple, which showed the fastest visual results was then compared to a retrospectively evaluated swine liver IRE dataset which had been obtained for similar conditions. The electroporated area of the apple and swine liver both showed a spherical geometry of comparable size. For all experiments, the standard protocol for human liver IRE was followed. To conclude, potato and apple were found to be suitable plant-based models for the visual evaluation of electroporated area after irreversible EP, with apple being the best choice for fast visual results. Given the comparable range, the size of the electroporated area of the apple may be promising as a quantitative predictor in animal tissue. Even if plant-based models cannot completely replace animal experiments, they can be used in the early stages of EP device development and testing, decreasing animal experiments to the necessary minimum.

Single-needle electroporation and interstitial electrochemotherapy: in vivo safety and efficacy evaluation of a new system.

OBJECTIVES: We conducted an in vivo trial to investigate the safety and efficacy of a newly developed system for the application of a combined therapy consisting of irreversible electroporation (IRE) and electrochemotherapy (IRECT) in the liver. The system is conceived as a single-needle multitined applicator with expandable electrodes that allow interstitial injection of fluids, e.g., chemotherapy. METHODS: Experiments were conducted in ten domestic pigs. The applicator was placed in different liver lobes under CT guidance. In one lobe, the applicator was used for conventional IRE (1500 V, 120 pulses, pulse length 100 µs). In the other lobe, the same procedure was performed preceded by the injection of a doxorubicin mixture through the expandable electrodes (IRECT). Contrast-enhanced CT and MRI were performed on days 1, 3, and 7 after the procedure. Accordingly, three animals were sacrificed on days 1, 3, and 7 after the imaging and ablation volumes were evaluated histopathologically. Related t test was used to compare the groups. RESULTS: Technical success was achieved in 9/10 experiments. One animal deceased during the intervention because of ventricular fibrillation. Follow-up CT 1 and 3 days after intervention showed a significant (p < 0.05) difference in the ablation volumes of IRECT vs IRE, respectively, of 4.47 ± 1.78 ml vs 2.51 ± 0.93 ml and of 3.39 ± 1.05 vs 1.53 ± 0.78 ml. CONCLUSIONS: IRECT using the newly developed system proved to be effective and provided significantly larger ablation volumes compared with IRE alone. However, ECG triggering is a necessary prerequisite to allow a safe application of the system. KEY POINTS: • Working on the geometry of the IRE applicator in terms of expandable electrodes may overcome the current limitations of IRE resulting from the placement of multiple electrodes. • Efficacy of IRE ablations can be enhanced by the interstitial application of chemotherapy in the periphery of ablation areas.

Electroporation of the Liver: More Than 2 Concurrently Active, Curved Electrodes Allow New Concepts for Irreversible Electroporation and Electrochemotherapy.

Irreversible electroporation and electrochemotherapy are 2 innovative electroporation-based minimally invasive therapies for the treatment of cancer. Combining nonthermal effects of irreversible electroporation with local application of chemotherapy, electrochemotherapy is an established treatment modality for skin malignancies. Since the application of electrochemotherapy in solid organs is a promising approach, this article describes a novel electrode configuration and field generating method. For the treatment of hepatic malignancies, the shape of the electric field should resemble a spherical 3-dimensional geometry around the target tissue inside the liver. To adapt the actual shape of the field, the probe is designed in computer-aided design with a live link to a computer simulation software: Changes in design can be revalued quickly, regarding different quality criteria for field strength inside and outside the tumor. To rate these criteria, a set of formulas with weighting coefficients has been included. As a result of this design process, a needle-shaped prototype applicator has been built, designed for an intracorporal electroporation-based treatment. It can be used as percutaneous, image-guided, minimally invasive treatment option for malignant liver tumors. The shaft of the probe is used as central electrode and fitted with additional 4 expandable electrodes. These satellite electrodes are hollow, thus serving as injectors for chemotherapeutic agents within the area of the electric field. This configuration can be used for electrochemotherapy as well as irreversible electroporation. By placing 5 electrodes with just one needle, the procedure duration as well as the radiation dose can be reduced tremendously. Additionally, the probe offers an option to adapt the field geometry to the tumor geometry by connecting the 5 electrodes to 5 individually chosen electric potentials: By fine-tuning the ablation zone via the potentials instead of adjusting the location of the electrode(s), the procedure duration as well as the radiation dose will decrease further.

Feasibility of electromagnetically guided transjugular intrahepatic portosystemic shunt procedure.

OBJECTIVES: To develop an electromagnetic navigation technology for transjugular intrahepatic portosystemic shunt (TIPS) creation and translate it from phantom to an in-vivo large animal setting. MATERIAL AND METHODS: A custom-designed device for TIPS creation consisting of a stylet within a 5 French catheter as well as a software prototype were developed that allow real-time tip tracking of both stylet and catheter using an electromagnetic tracking system. Feasibility of navigated TIPSS creation was tested in a phantom by two interventional radiologists (A/B) followed by in-vivo testing evaluation in eight domestic pigs. Procedure duration and number of attempts needed for puncture of the portal vein were recorded. RESULTS: In the phantom setting, intervention time to gain access to the portal vein (PV) was 144 ± 67 s (A) and 122 ± 51 s (B), respectively. In the in-vivo trials, TIPS could be successfully completed in five out of eight animals. Mean time for the complete TIPS was 245 ± 205 minutes with a notable learning curve towards the last animal. CONCLUSIONS: TIPS creation with the use of electromagnetic tracking technology proved to be feasible in-vitro as well as in-vivo. The system may be useful to facilitate challenging TIPSS procedures.

Animal experimental evaluation of a new sealing device for indwelling arterial catheters.

BACKGROUND: Hematoma is a common complication following arterial puncture. To date no device that allows sealing of an arterial puncture site with in-situ catheter has been developed. PURPOSE: To evaluate a newly developed arterial sealing device for endovascular catheters in an in-vivo experimental setting. MATERIAL AND METHODS: A peelable collagen-based vascular sealing device for endovascular catheters was tested in acute (follow-up: 4 h; n = 2) and chronic (follow-up: 1 week; n = 4) settings in the femoral artery (FA) of sheep. After implantation correct position of the device as well as patency of the FA were verified angiographically. In the chronic group, hematoma was excluded and patency of FA was assured using color Doppler ultrasound 1 and 3 days after the procedure. After 1 week a final ultrasound and an angiography were performed for final evaluation. Thereafter, the animals were sacrificed and the puncture site was dissected and analyzed macroscopically. RESULTS: Sufficient sealing of the puncture site could be observed in all animals. In acute and chronic experiments, neither a hematoma at the puncture site nor other complications were observed after positioning the sealing device. Follow-up color Doppler ultrasounds (CDUS) and final angiography revealed patent FAs in all animals. Macroscopic evaluation of dissection material proved collagen plug and catheter being in place. CONCLUSION: Our preliminary in-vivo results demonstrate a safe and convenient vascular sealing system for endovascular catheters. No acute or chronic complications were observed.

Detecting endoleaks after endovascular AAA repair with a minimally invasive, implantable, telemetric pressure sensor: an in vitro study.

A feasibility study on a completely digital telemetric pressure sensor (TPS) to detect endoleaks was performed in an in vitro model of an abdominal aortic aneurysm (AAA). An endovascular-stented AAA silicone model with different types (I-III) and sizes (3-11 French) of endoleaks was created and pulsatile pressure was applied with physiological flow and pressure rates [mean intraaortic pressure (IAP): 95-130 mmHg] and different degrees of thrombosis of the aneurysm sac. Aneurysm sac pressure (ASP) was measured with the TPS and with wired pressure sensors (WPS) as a reference. Statistical analysis included paired t-test, Pearson's correlation analysis and Bland-Altman plots. After opening an endoleak, the mean ASP increased significantly (P < 0.0001) from 15 to almost 95% of the mean IAP depending on endoleak type and size. ASP could be measured accurately with the TPS and the WPS. The telemetric and wired ASP increase showed a high Pearson's correlation coefficient (r) for a non-thrombosed (r = 0.97) and a thrombosed (r = 0.96) aneurysm sac. In an in vitro silicone model, the newly designed telemetric pressure sensor was able to detect the occurrence of an endoleak in a non-invasive way and might be a valuable device for follow-up of endovascular AAA repair.

Temporary pulmonary stent placement as emergency treatment of pulmonary embolism: first experimental evaluation.

OBJECTIVES: We aimed to evaluate the performance of a newly designed temporary stent device as a percutaneous emergency treatment of pulmonary embolism. BACKGROUND: If thrombolysis is contraindicated or recanalization by thrombolysis delayed in patients with severe pulmonary embolism who are threatened by acute circulatory failure, percutaneous temporary pulmonary stent placement may represent an additional option before surgical embolectomy is considered. METHODS: The newly designed temporary pulmonary stent is made from woven Nitinol and has a distal blunt end and a proximal crimped end, which is firmly fixed to a 0.035-inch guidewire. It is delivered through a 9.5-F polytetrafluoroethylene sheath using a pusher tube. Stent placement and removal were examined in 9 anesthetized sheep with experimentally induced pulmonary embolism. Hemodynamic parameters were recorded in 7 animals. RESULTS: Delivery and removal of the stent was uneventful and rapidly accomplished. Stent placement was associated with a significant decrease in Miller angiographic index (from 11.2 +/- 3.1 to 3.8 +/- 1.9; p = 0.0001), heart rate (from 139 +/- 35 beats/min to 92 +/- 11 beats/min; p = 0.0129), and mean pulmonary artery pressure (from 32 +/- 14 mm Hg to 21 +/- 14 mm Hg; p = 0.0029) and a significant increase in mean aortic pressure (from 48 +/- 14 mm Hg to 61 +/- 8 mm Hg; p = 0.0080). Autopsy revealed neither wall damage nor parenchymal hemorrhage. CONCLUSIONS: Our preliminary study proves the technical feasibility of temporary placement and removal of a newly designed dedicated pulmonary stent to recanalize centrally located embolic occlusions in severe pulmonary embolism. Animal experimental evaluation revealed rapid and significant circulatory improvement after stent placement.

An expandable percutaneous catheter pump for left ventricular support: proof of concept.

OBJECTIVES: We sought to evaluate the performance of a newly designed percutaneous catheter with expandable pump. BACKGROUND: The device was designed as a percutaneously insertable temporary support system for patients with acute left ventricular failure. METHODS: The pump catheter (introduction diameter 9-F) is positioned in the left ventricle. The rotor is driven by an external motor through a flexible drive shaft. A model circuit was used to assess pump performance, hemolysis tests, and particle image velocimetry. The feasibility of the catheter placement and pump operation were examined in 12 anesthetized sheep. Cardiogenic shock was induced in seven of the animals. Cardiac output (CO) and mean aortic blood pressure (MAP) were recorded before and during shock, and during catheter pump action. RESULTS: The catheter pump delivered a flow of 4.1 l/min at a differential pressure of 60 mm Hg. The average modified index of hemolysis was 11.6 (optimum, 1.8). Fluoroscopically and echocardiographically guided in vivo placement and deployment of the device were quick and uncomplicated. Under simulation of acute left ventricular failure (CO 43 +/- 22% and MAP 55 +/- 16% of the baseline value), the catheter pump significantly improved CO to 67 +/- 12% and MAP to 74 +/- 18%. Maximum in vivo duration of operation was 6 h (average, 3.1 +/- 1.4 h). These animal studies revealed: 1) no significant hemolysis (average plasma-free hemoglobin 26 +/- 4 mg/l after 3 h); 2) no thrombotic deposits at rotor or pump housing; and 3) no damage to the endocardium or aortic valve. CONCLUSIONS: A percutaneously insertable, expandable catheter pump is technically and clinically feasible. Our first experimental results are encouraging.

Percutaneous venous thrombectomy using the Arrow-Trerotola percutaneous thrombolytic device (PTD) with temporary caval filtration: in vitro investigations.

PURPOSE: To evaluate the size and quantity of downstream emboli after thrombectomy using the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with or without temporary filtration for extensive iliofemoral and iliocaval thrombi in an in vitro flow model. METHODS: Iliocaval thrombi were simulated by clotted bovine blood in a flow model (semilucent silicone tubings, diameter 12-16 mm). Five experimental set-ups were performed 10 times each; thrombus particles and distribution were measured in the effluent. First, after retrograde insertion, mechanical thrombectomy was performed using the PTD alone. Then a modified self-expanding tulip-shaped temporary vena cava stent filter was inserted additionally at the beginning of each declotting procedure and removed immediately after the intervention without any manipulation within or at the filter itself. In a third step, the filter was filled with thrombus only. Here, two experiments were performed: Careful closure within the flow circuit without any additional fragmentation procedure and running the PTD within the filter lumen, respectively. In the final set-up, mechanical thrombectomy was performed within the thrombus-filled tubing as well as in the filter lumen. The latter was closed at the end of the procedure and both devices were removed from the flow circuit. RESULTS: Running the PTD in the flow circuit without filter protection led to a fragmentation of 67.9% (+/-7.14%) of the clot into particles < or =500 microm; restoration of flow was established in all cases. Additional placement of the filter safely allowed maceration of 82.9% (+/-5.59%) of the thrombus. Controlled closure of the thrombus-filled filter within the flow circuit without additional mechanical treatment broke up 75.2% (+/-10.49%), while additional mechanical thrombectomy by running the PTD within the occluded filter led to dissolution of 90.4% (+/-3.99%) of the initial clot. In the final set-up, an overall fragmentation rate of 99.6% (+/-0.44%) was achieved. CONCLUSIONS: The combined use of the Arrow-Trerotola PTD and a temporary vena cava stent filter proved to be effective for even large clot removal in this experimental set-up.

MR-guided percutaneous intramyocardial injection with an MR-compatible catheter: feasibility and changes in T1 values after injection of extracellular contrast medium in pigs.

PURPOSE: To assess the feasibility of percutaneous magnetic resonance (MR)-guided intramyocardial injection of gadodiamide by using real-time imaging and to quantify T1 values and the size of the enhanced region for different concentrations of contrast agent for 30 minutes after injection. MATERIALS AND METHODS: Animal care committee approval was obtained. A catheter with a needle tip was advanced into the left ventricle in seven pigs by using real-time imaging with radial steady-state free precession. After intramyocardial injection of 2 mL of solution at concentrations of 0.05 or 0.10 mmol/mL gadodiamide, local changes in T1 values and size of the contrast material-enhanced region were sequentially measured at 3, 15, and 30 minutes after injection by using the Look-Locker sequence. Two-tailed paired Student t tests were used for statistical analysis. RESULTS: Catheter guidance and visualization of contrast agent distribution were feasible in all animals. Regional changes in T1 values were significantly different for different contrast agent concentrations (for 0.05 mmol/mL, 456 msec +/- 5 [+/- standard error of the mean]; for 0.10 mmol/mL, 228 msec +/- 4; P < .001) measured 3 minutes after injection. T1 values increased significantly (P < .05) to 720 msec +/- 7 for 0.05 mmol/mL gadodiamide and 445 msec +/- 6 for 0.10 mmol/mL gadodiamide 30 minutes after injection but remained significantly lower than those of remote myocardium (879 msec +/- 8). The size of the contrast-enhanced region increased from 13 mm(2) +/- 2 at 3 minutes to 30 mm(2) +/- 3 at 30 minutes (P < .05). CONCLUSION: Catheter MR-guided percutaneous intramyocardial injection is feasible; after intramyocardial injection of gadodiamide at concentrations of 0.05 and 0.10 mmol/mL, T1 values decreased over the observation time.

Noninvasive extracorporeal thrombolysis using electrical discharge-induced shock waves: in vitro experiments.

RATIONALE AND OBJECTIVES: Many thrombectomy approaches have been developed for the treatment of venous thrombosis; however, no reference standard exists at this time. The aim of this study was to evaluate the efficacy of the transcutaneous application of electrical discharge-induced shock waves for thrombolysis in an in vitro model. METHODS: Shock waves were applied on a thrombus positioned in a plasma-containing silicon tube using 2 different energy flux densities (0.53 and 2.26 mJ/mm). Depending upon the specific experiment, the thrombus was slightly moved to mimic pulsatory motions or/and additional Actilyse was added. Plasma samples were taken to determine the d-dimers before and after the application of shock waves. RESULTS: Energy of 0.53 mJ/mm was insufficient for thrombolysis whereas the energy of 2.26 mJ/mm yielded a removal rate of up to 76.4% when the thrombus was slightly moved during the procedure. The amount of d-dimers correlated well with the addition of Actilyse. However, this did not affect the removal rate significantly. CONCLUSION: The results demonstrate the potential of electrical discharge-induced shock waves for thrombolysis.