PIRET-A Platform for Treatment Planning in Electroporation-Based Therapies.

Tissue electroporation is the basis of several therapies. Electroporation is performed by briefly exposing tissues to high electric fields. It is generally accepted that electroporation is effective where an electric field magnitude threshold is overreached. However, it is difficult to preoperatively estimate the field distribution because it is highly dependent on anatomy and treatment parameters. OBJECTIVE: We developed PIRET, a platform to predict the treatment volume in electroporation-based therapies. METHODS: The platform seamlessly integrates tools to build patient-specific models where the electric field is simulated to predict the treatment volume. Patient anatomy is segmented from medical images and 3D reconstruction aids in placing the electrodes and setting up treatment parameters. RESULTS: Four canine patients that had been treated with high-frequency irreversible electroporation were retrospectively planned with PIRET and with a workflow commonly used in previous studies, which uses different general-purpose segmentation (3D Slicer) and modeling software (3Matic and COMSOL Multiphysics). PIRET outperformed the other workflow by 65 minutes (× 1.7 faster), thanks to the improved user experience during treatment setup and model building. Both approaches computed similarly accurate electric field distributions, with average Dice scores higher than 0.93. CONCLUSION: A platform which integrates all the required tools for electroporation treatment planning is presented. Treatment plan can be performed rapidly with minimal user interaction in a stand-alone platform. SIGNIFICANCE: This platform is, to the best of our knowledge, the most complete software for treatment planning of irreversible electroporation. It can potentially be used for other electroporation applications.

Powering Electronic Implants by High Frequency Volume Conduction: In Human Validation.

OBJECTIVE: Wireless power transfer (WPT) is used as an alternative to batteries to accomplish miniaturization in electronic medical implants. However, established WPT methods require bulky parts within the implant or cumbersome external systems, hindering minimally invasive deployments and the development of networks of implants. As an alternative, we propose a WPT approach based on volume conduction of high frequency (HF) current bursts. These currents are applied through external electrodes and are collected by the implants through two electrodes at their opposite ends. This approach avoids bulky components, enabling the development of flexible threadlike implants. METHODS: We study in humans if HF (6.78 MHz) current bursts complying with safety standards and applied through two textile electrodes strapped around a limb can provide substantial powers from pairs of implanted electrodes. RESULTS: Time averaged electric powers obtained from needle electrodes (diameter = 0.4 mm, length = 3 mm, separation = 30 mm) inserted into arms and lower legs of five healthy participants were 5.9 ± 0.7 mW and 2.4 ± 0.3 mW respectively. We also characterize the coupling between the external system and the implants using personalized two-port impedance models generated from medical images. CONCLUSIONS: The results demonstrate that innocuous and imperceptible HF current bursts that flow through the tissues by volume conduction can be used to wirelessly power threadlike implants. SIGNIFICANCE: This is the first time that WPT based on volume conduction is demonstrated in humans. This method overcomes the limitations of existing WPT methods in terms of minimal invasiveness and usability.

Modeling Methods for Treatment Planning in Overlapping Electroporation Treatments.

OBJECTIVE: Irreversible electroporation (IRE) is a non-thermal tissue ablation therapy which is induced by applying high voltage waveforms across electrode pairs. When multiple electrode pairs are sequentially used, the treatment volume (TV) is typically computed as the geometric union of the TVs of individual pairs. However, this method neglects that some regions are exposed to overlapping treatments. Recently, a model describing cell survival probability was introduced which effectively predicted TV with overlapping fields in vivo. However, treatment overlap has yet to be quantified. This study characterizes TV overlap in a controlled in vitro setup with the two existing methods which are compared to an adapted logistic model proposed here. METHODS: CHO cells were immobilized in agarose gel. Initially, we characterized the electric field threshold and the cell survival probability for overlapping treatments. Subsequently, we created a 2D setup where we compared and validated the accuracy of the different methods in predicting the TV. RESULTS: Overlap can reduce the electric field threshold required to induce cell death, particularly for treatments with low pulse number. However, it does not have a major impact on TV in the models assayed here, and all the studied methods predict TV with similar accuracy. CONCLUSION: Treatment overlap has a minor influence in the TV for typical protocols found in IRE therapies. SIGNIFICANCE: This study provides evidence that the modeling method used in most pre-clinical and clinical studies seems adequate.

Segmentation of the placenta and its vascular tree in Doppler ultrasound for fetal surgery planning.

PURPOSE: Twin-to-twin transfusion syndrome (TTTS) is a serious condition that occurs in about 10-15% of monochorionic twin pregnancies. In most instances, the blood flow is unevenly distributed throughout the placenta anastomoses leading to the death of both fetuses if no surgical procedure is performed. Fetoscopic laser coagulation is the optimal therapy to considerably improve co-twin prognosis by clogging the abnormal anastomoses. Notwithstanding progress in recent years, TTTS surgery is highly risky. Computer-assisted planning of the intervention can thus improve the outcome. METHODS: In this work, we implement a GPU-accelerated random walker (RW) algorithm to detect the placenta, both umbilical cord insertions and the placental vasculature from Doppler ultrasound (US). Placenta and background seeds are manually initialized in 10-20 slices (out of 245). Vessels are automatically initialized in the same slices by means of Otsu thresholding. The RW finds the boundaries of the placenta and reconstructs the vasculature. RESULTS: We evaluate our semiautomatic method in 5 monochorionic and 24 singleton pregnancies. Although satisfactory performance is achieved on placenta segmentation (Dice ≥ 84.0%), some vascular connections are still neglected due to the presence of US reverberation artifacts (Dice ≥ 56.9%). We also compared inter-user variability and obtained Dice coefficients of ≥ 76.8% and ≥ 97.42% for placenta and vasculature, respectively. After a 3-min manual initialization, our GPU approach speeds the computation 10.6 times compared to the CPU. CONCLUSIONS: Our semiautomatic method provides a near real-time user experience and requires short training without compromising the segmentation accuracy. A powerful approach is thus presented to rapidly plan the fetoscope insertion point ahead of TTTS surgery.

EView: An electric field visualization web platform for electroporation-based therapies.

BACKGROUND AND OBJECTIVES: Electroporation is the phenomenon by which cell membrane permeability to ions and macromolecules is increased when the cell is briefly exposed to high electric fields. In electroporation-based treatments, such exposure is typically performed by delivering high voltage pulses across needle electrodes in tissue. For a given tissue and pulsing protocol, an electric field magnitude threshold exists that must be overreached for treatment efficacy. However, it is hard to preoperatively infer the treatment volume because the electric field distribution intricately depends on the electrodes' positioning and length, the applied voltage, and the electric conductivity of the treated tissues. For illustrating such dependencies, we have created EView (https://eview.upf.edu), a web platform that estimates the electric field distribution for arbitrary needle electrode locations and orientations and overlays it on 3D medical images. METHODS: A client-server approach has been implemented to let the user set the electrode configuration easily on the web browser, whereas the simulation is computed on a dedicated server. By means of the finite element method, the electric field is solved in a 3D volume. For the sake of simplicity, only a homogeneous tissue is modeled, assuming the same properties for healthy and pathologic tissues. The non-linear dependence of tissue conductivity on the electric field due to the electroporation effect is modeled. The implemented model has been validated against a state of the art finite element solver, and the server has undergone a heavy load test to ensure reliability and to report execution times. RESULTS: The electric field is rapidly computed for any electrode and tissue configuration, and alternative setups can be easily compared. The platform provides the same results as the state of the art finite element solver (Dice = 98.3 ± 0.4%). During the high load test, the server remained responsive. Simulations are computed in less than 2 min for simple cases consisting of two electrodes and take up to 40 min for complex scenarios consisting of 6 electrodes. CONCLUSIONS: With this free platform we provide expert and non-expert electroporation users a way to rapidly model the electric field distribution for arbitrary electrode configurations.