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.11Ysciescopu

Effect of duty cycles of tumor‑treating fields on glioblastoma cells and normal brain organoids

Tumor‑treating fields (TTFields) are emerging cancer therapies based on alternating low‑intensity electric fields that interfere with dividing cells and induce cancer cell apoptosis. However, to date, there is limited knowledge of their effects on normal cells, as well as the effects of different duty cycles on outcomes. The present study evaluated the effects of TTFields with different duty cycles on glioma spheroid cells and normal brain organoids. A customized TTFields system was developed to perform in vitro experiments with varying duty cycles. Three duty cycles were applied to three types of glioma spheroid cells and brain organoids. The efficacy and safety of the TTFields were evaluated by analyzing the cell cycle of glioma cells, and markers of neural stem cells (NSCs) and astrocytes in brain organoids. The application of the TTFields at the 75 and 100% duty cycle markedly inhibited the proliferation of the U87 and U373 compared with the control. FACS analysis revealed that the higher the duty cycle of the applied fields, the greater the increase in apoptosis detected. Exposure to a higher duty cycle resulted in a greater decrease in NSC markers and a greater increase in glial fibrillary acidic protein expression in normal brain organoids. These results suggest that TTFields at the 75 and 100% duty cycle induced cancer cell death, and that the neurotoxicity of the TTFields at 75% was less prominent than that at 100%. Although clinical studies with endpoints related to safety and efficacy need to be performed before this strategy may be adopted clinically, the findings of the present study provide meaningful evidence for the further advancement of TTFields in the treatment of various types of cancer.11Nsciescopu

Optimization Framework for Temporal Interference Current Tibial Nerve Stimulation in Tibial Nerves Based on In-Silico Studies

Compared to the existing noninvasive methods, temporal interference (TI) current stimulation is an emerging noninvasive neuromodulation technique that can improve the ability to focus an electrical field on a target nerve. Induced TI field distribution depends on the anatomical structure of individual neurons, and thus the electrode and current optimization to enhance the field focus must reflect these factors. The current study presents a TI field optimization framework for focusing the stimulation energy on the target tibial nerve through extensive electrical simulations, factoring in individual anatomical differences. We conducted large-scale in-silico experiments using realistic models based on magnetic resonance images of human subjects to evaluate the effectiveness of the proposed methods for tibial nerve stimulation considering overactive bladder (OAB) treatment. The electrode position and current intensity were optimized for each subject using an automated algorithm, and the field-focusing performance was evaluated based on the maximum intensity of the electric fields induced at the target nerve compared with the electric fields in the neighboring tissues. Using the proposed optimization framework, the focusing ability increased by 12% when optimizing the electrode position. When optimizing both the electrode position and current, this capability increased by 11% relative to electrode position optimization alone. These results suggest the significance of optimizing the electrode position and current intensity for focusing TI fields at the target nerve. Our electrical simulation-based TI optimization framework can be extended to enable personalized peripheral nerve stimulation therapy to modulate peripheral nerves.11Ysciescopu

In Vitro Study of Neurochemical Changes Following Low-Intensity Magnetic Stimulation

Given its ability to modulate neuronal excitability, low-intensity magnetic stimulation (LIMS) has therapeutic potential in the treatment of neurological disorders. However, the underlying of LIMS effects remain poorly understood because LIMS does not directly generate action potentials. We aimed to elucidate these mechanisms by studying and systematically comparing the neurochemical changes induced in vitro by LIMS. To this end, we developed a simple in vitro magnetic stimulation device that allowed delivery of a range of stimulation parameters in order to generate sufficient field intensity for the subthreshold. In characterizing our custom-built system, we conducted computational simulations to determine the electromagnetic field exposure to a cell culture dish. Subsequently, using the custom-built LIMS system, we applied three different stimulation protocols to differentiated neuroblastoma cells for 30 min and then assessed the resultant neurochemical changes. We found that high-frequency (HF: 10 Hz) stimulation increased levels of the excitatory neurotransmitter, glutamate, while low-frequency (LF: 1 Hz) stimulation increased levels of the inhibitory neurotransmitter, GABA. These results suggest that LIMS effects are frequency-dependent: suppression of neuroexcitability occurs at LF and facilitation occurs at HF. Furthermore, we observed pattern-dependent changes when comparing repetitive high-frequency (rHF) and intermittent high-frequency (iHF) stimulations: iHF took more time to induce neurochemical change than rHF. In addition, we found that calcium changes were closely associated with glutamate changes in response to different stimulation parameters. Our experimental findings indicate that LIMS induces the release of neurotransmitters and affects neuronal excitability at magnetic field intensities far lower than suprathreshold, and that this in turn induces action potentials. Therefore, this study provides a cellular framework for understanding how low-intensity magnetic stimulation could affect clinical outcomes.11Ysciescopu

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.1

Fabrication of a flexible three-dimensional hybrid directional lead for deep brain stimulation and control of micturition reflex in rats

11Ysciescopu