Circular Radio-Frequency Electrode With MEMS Temperature Sensors for Laparoscopic Renal Sympathetic Denervation.

OBJECTIVE: Laparoscopic renal denervation (LRDN) ablates sympathetic nerves on the outer wall of a renal artery to treat autonomic nervous system disorders such as hypertension and arrhythmia. Here, we developed a new circular radio frequency (RF) electrode for LRDN using micro-electro-mechanical systems (MEMS) technology. METHODS: The electrode consists of a parallel bipolar MEMS electrode, two MEMS thermocouples, and a shape-memory alloy (SMA) substrate. The electrode is automatically wrapped and unwrapped under actuation controlled by the heat generated by RF energy on the electrode-tissue interface. The electrode was designed through a computational simulation analysis, and its actuation and temperature-sensing performance were tested in laboratory experiments and a porcine animal study. RESULTS: In an in-vivo study of porcine renal arteries, the electrode could automatically wrap and unwrap around an artery during LRDN. The bipolar MEMS electrode required 13 Vrms for heat generation up to 60°C, while the two MEMS thermocouples reliably measured the temperature without noise signals (a temperature coefficient of 38.3 or 38.5 µV/°C and an accuracy of ±0.44 or ±0.49°C). As revealed in a histological analysis using hematoxylin and eosin staining and Masson's trichrome staining, the renal artery was intact after LRDN. CONCLUSION: The circular RF electrode improves the safety of LRDN by reliably measuring the electrode temperature of the electrode during RDN and enhances the effectiveness of LRDN by reducing the complicated manipulations of the surgical instrument. SIGNIFICANCE: The developed circular RF electrode will pave the way for LRDN treatment of autonomic nervous system disorders.

Laparoscopic Ablation System for Complete Circumferential Renal Sympathetic Denervation.

GOAL: The catheter-based renal denervation (RDN) showed promising results for patients in lowering BP, but there were also many non-responders. One of the possible reasons was the incomplete neural ablation due to the ablation of renal nerves at random sites resulting in asymmetric innervation patterns along the renal artery. METHODS: We developed a laparoscopic ablation system that is optimized for complete RDN regardless of renal arterial innervation and size. To demonstrate its effectiveness, we evaluated the system using computational simulation and 28-day survival model using pigs. RESULTS: The ablations were focused around the tunica externa, and the ablation patterns could be predicted numerically during RDN treatment. In the animal study, the mean reduction of systolic BP and diastolic BP in the bilateral main renal arteries was 22.8 mmHg and 14.4 mmHg (P<0.001), respectively. The respond to immunostaining targeting tyrosine hydroxylase was significantly reduced at treatment site (108.2 ± 7.5 (control) vs. 63.4 ± 8.7 (treatment), P<0.001), and an increased degree of sympathetic signals interruption to kidneys was associated with the efficacy of RDN. CONCLUSION: The laparoscopic ablation system achieved complete circumferential RDN at the treatment site and could numerically predict the ablation patterns. SIGNIFICANCE: These findings clearly suggest that the proposed system can significantly improve the RDN effectiveness by reducing the variation to the percentage of injured nerves and open up a new opportunity to treat uncontrolled hypertension.

Thermal Ablation and High-Resolution Imaging Using a Back-to-Back (BTB) Dual-Mode Ultrasonic Transducer: In Vivo Results.

We present a back-to-back (BTB) structured, dual-mode ultrasonic device that incorporates a single-element 5.3 MHz transducer for high-intensity focused ultrasound (HIFU) treatment and a single-element 20.0 MHz transducer for high-resolution ultrasound imaging. Ultrasound image-guided surgical systems have been developed for lesion monitoring to ensure that ultrasonic treatment is correctly administered at the right locations. In this study, we developed a dual-element transducer composed of two elements that share the same housing but work independently with a BTB structure, enabling a mode change between therapy and imaging via 180-degree mechanical rotation. The optic fibers were embedded in the HIFU focal region of ex vivo chicken breasts and the temperature change was measured. Images were obtained in vivo mice before and after treatment and compared to identify the treated region. We successfully acquired B-mode and C-scan images that display the hyperechoic region indicating coagulation necrosis in the HIFU-treated volume up to a depth of 10 mm. The compact BTB dual-mode ultrasonic transducer may be used for subcutaneous thermal ablation and monitoring, minimally invasive surgery, and other clinical applications, all with ultrasound only.

Quantitative analysis of renal arterial variations affecting the eligibility of catheter-based renal denervation using multi-detector computed tomography angiography.

Catheter-based renal denervation (RDN) was introduced to treat resistant hypertension. However, the reduction in blood pressure after the RDN was modest. Catheter-based RDN was performed only at main renal arteries, except for accessory and branch arteries due to the diameter being too small for the catheter to approach. Here, we retrospectively analyzed the anatomy of diverse renal arteries via 64-channel multi-detector computed tomography angiograms of 314 consecutive donors who underwent living donor nephrectomy from January 2012 to July 2017. Occurrence rates of one or more accessory renal arteries in donors were 25.3% and 19.4% on the left and right sides, respectively. Early branching rates before 25 mm from the aorta to the right and left renal arteries were 13.7% and 10.5%, respectively. Overall, 63.1% and 78.3% of donors had no accessory artery bilaterally and no branched renal artery, respectively. As a result, 47.1% had only main renal arteries without an accessory artery and early-branching artery. Approximately half of the donors had multiple small renal arteries bilaterally, for which catheter-based denervation may not be suitable. Thus, preoperative computed tomography angiography requires careful attention to patient selection, and there is a need for improved methods for denervation at various renal arteries.

Development of a nitinol-actuated surgical instrument for laparoscopic renal denervation: feasibility test in a swine survival model.

Purpose: In this study, we developed a novel nitinol-actuated surgical instrument to conduct laparoscopic renal denervation for the treatment of resistant hypertension. We investigated whether shape and temperature settings of nitinol specimens fit well into the design goals. Furthermore, we conducted a pilot study to validate the mechanical and physiological performance of nerve ablation without damaging the renal artery.Method: Tensile tests were performed to observe temperature-dependent thermomechanical properties and the original shape of nitinol specimens was set considering our design goal. We performed strain gage experiments to measure bending strain. We developed surgical instrument and operated laparoscopic renal denervation in a swine model. Subsequent impedance spectroscopy experiments were conducted to measure changes in impedance magnitudes during the operation and histological analyses were performed to visualize thermogenic damage to arteries and nerves.Results: Tensile testing showed that the shape memory effect begins above 37 °C. Measured strains on nitinol surfaces were 2.10% ± 0.769%, below the strain limit of 8%. Impedance spectroscopy experiments showed decreases in magnitude in all six trials. After operation of laparoscopic renal denervation following the protocol, renal arteries and nerves were harvested and thermogenic damage was observed in nerves but not arteries.Conclusion: We developed a novel nitinol-actuated surgical instrument with which to perform laparoscopic renal denervation. The feasibility of our device was verified using thermomechanical analyses of nitinol, and assessments of mechanical and physiological performance. Our device could be used in other laparoscopic procedures that require large degrees of freedom while restricting to trocar size.

Laparoscopic Renal Denervation System for Treating Resistant Hypertension: Overcoming Limitations of Catheter-Based Approaches.

GOAL: In a pivotal clinical trial, the percutaneous catheter-based renal denervation system developed to treat resistant hypertension did not show effectiveness in reducing blood pressure because of its fundamental limitation to ablate deeper nerves present around the renal artery. METHODS: We propose a new renal denervation strategy called laparoscopicdenervation system (LDS) based-on laparoscopy procedure to ablate the renal nerves completely but inhibit the thermal arterial damage.The system has flexible electrodes to bend around the arterial wall to ablate nervesThe simulation study using validated in-silico models evaluated the heat distributionon the outer arterial wall,and an acute animal study (swine model) was conducted to demonstrate the feasibility of LDS in vivo. RESULTS: The simulation studyconfirmedthat LDS could localize the heat distributionbetween the electrode and the outer arterial wall. In the animal study, we could maximize nerve denervation by the localizing ablation energy within the renal nerves and achieve nerve denaturationand decrease in neural density by 20.78% (P < 0.001), while maintaining a constant tip temperature of 65 °C for the duration of 70 s treatment. The study confirmed intact lumen artery through histological analysis and acute reduction in systolic blood pressure by 9.55 mmHg (p < 0.001) Conclusion: The LDS presented here has potential to effectively and safely ablate the renal nerves, independent of anatomical variation and nerve distribution, to control hypertension in real clinical conditions. SIGNIFICANCE: LDS approach is innovative, inventive, and presents a novel technique totreat hypertension.

Animal model evaluation of a novel renal denervation system for future laparoscopic treatment of resistant hypertension.

Purpose: Although percutaneous catheter-based ablation of renal sympathetic nerve fibers has been used in the treatment of patients with resistant hypertension, a recent phase III study did not confirm its efficacy. In this study, we developed a novel laparoscopic renal denervation system and evaluated its safety and initial feasibility using an animal model. Materials and Methods: A novel surgical instrument that uses a smart algorithm with temperature-monitoring feedback was developed. We used 4 male pigs (6 weeks old, weighing approximately 45 kg each) to evaluate the safety and efficacy of the laparoscopic renal denervation system. We performed immunohistochemical staining analysis after renal denervation using various tip temperatures and over various durations through an open approach. Results: When the temperature of the outer wall of the renal artery was maintained at 90℃ for 180 seconds, the artery was completely denervated without damaging its inner layer, as evaluated using Masson's trichrome staining. When the temperature ranged from 70℃ to 90℃ and the duration ranged from 90 to 420 seconds, partial or complete denervation without significant vessel injury was confirmed with anti- growth-associated protein 43 and anti-S100 staining. Conclusions: This animal study confirmed the safety and feasibility of the novel laparoscopic renal denervation system. A safe and effective protocol was developed with ablation at a constant tissue temperature of 70℃ to 90℃ within 180 seconds. However, further developments are necessary before its clinical use.

Developing a Computational Model of Renal Nerves and Surgical System for Laparoscopic Renal Denervation.

The sympathetic nervous system was known to play an important role in resistant hypertension. Surgical sympathectomy for renal sympathetic nerve removal were performed since the 1930s. Although effective, it had many serious side effects and complications due to non-selective property. Recently, catheter based RDN system using radiofrequency (RF) ablation was developed and considered promising, however, it failed in sham controlled trial. Therefore, there are needs for safe and effective RDN strategies considering the anatomical structure of the renal arteries and sympathetic nerves. In this paper, we propose a novel surgical instruments for laparoscopic renal denervation (RDN) to treat of resistant hypertension through a 3D realistic model using nephrectomy tissues. Laparoscopic RDN is a new surgical approach to remove renal sympathetic nerves.

Design and simulation of novel laparoscopic renal denervation system: a feasibility study.

PURPOSE: In this study, we propose a novel laparoscopy-based renal denervation (RDN) system for treating patients with resistant hypertension. In this feasibility study, we investigated whether our proposed surgical instrument can ablate renal nerves from outside of the renal artery safely and effectively and can overcome the depth-related limitations of the previous catheter-based system with less damage to the arterial walls. METHOD: We designed a looped bipolar electrosurgical instrument to be used with laparoscopy-based RDN system. The tip of instrument wraps around the renal artery and delivers the radio-frequency (RF) energy. We evaluated the thermal distribution via simulation study on a numerical model designed using histological data and validated the results by the in vitro study. Finally, to show the effectiveness of this system, we compared the performance of our system with that of catheter-based RDN system through simulations. RESULTS: Simulation results were within the 95% confidence intervals of the in vitro experimental results. The validated results demonstrated that the proposed laparoscopy-based RDN system produces an effective thermal distribution for the removal of renal sympathetic nerves without damaging the arterial wall and addresses the depth limitation of catheter-based RDN system. CONCLUSIONS: We developed a novel laparoscope-based electrosurgical RDN method for hypertension treatment. The feasibility of our system was confirmed through a simulation study as well as in vitro experiments. Our proposed method could be an effective treatment for resistant hypertension as well as central nervous system diseases.