GATE Simulation Research Articles

Evaluation of Modular J-PET sensitivity

The Modular J-PET represents the latest advancement in the Jagiellonian-PET series, utilizing extended plastic scintillator strips. This prototype's modular design enables cost-effective imaging of multi-photon annihilation and positronium, allowing for easy assembly, portability, and versatility. Additionally, its lightweight construction facilitates static bed examinations with a mobile detection system that can be positioned conveniently alongside the patient, negating the requirement for spacious clinical settings. Comprising 24 modules arranged in regular 24- sided polygons circumscribing a 73.9 cm diameter circle, each module integrates 13 scintillator strips, measuring 50 cm in length and 6mm×24mm in cross-section. Scintillation light is captured at both ends through analog Silicon Photomultipliers (SiPMs). This research presents Sensitivity of the Modular J-PET tomograph, adhering to the NEMA_NU 2-2018 standards. Sensitivity measurement was performed with 〖^68〗Geline source inside the 5 sleeves aluminium phantom placed at center of the detector`s FOV and 10 cm offset from the center of detector. Analyzing the gathered data involved employing the specialized J-PET Framework software, developed within the C++ architecture. To validate the experimental findings, comparisons were made with GATE simulations, wherein the source and phantom were emulated in the same configuration as employed in the actual experiment.

Simulasi Gerbang Logika Dengan Menggunakan Aplikasi Zeliosoft 2

The background for carrying out this research is to create a logic gate simulation using a PLC (Programmable Logic Controlled) application, namely using the Zeliosoft 2 application, thereby reducing the risk of damage when creating electronic circuits manually. The aim of this research is to show the effectiveness of logic gates and how to operate them using the Zeliosoft 2 program. This research uses a simulation approach with a laptop running the Zelio Soft 2 program in the Electrical Engineering Vocational Education laboratory. The results obtained show that the simulation results carried out on the application are in accordance with the logic gate truth table. This is proven by the data produced in the research on each logic gate which is simulated according to the truth table.

A simulation of a high-resolution cadmium zinc telluride positron emission tomography system.

A CZT (cadmium zinc telluride) PET (positron emission tomography) system is being developed at Stanford University. CZT has the promise of outperforming scintillator-based systems in energy and spatial resolution but has relatively poor coincidence timingresolution. To supplement GATE (GEANT 4 Application for Emission Tomography) simulations with charge transport and electronics modeling for a high-resolution CZT PET system. A conventional GATE simulation was supplemented with electron-hole transport modeling and experimentally measured single detector energy resolution to improve the system-level understanding of a CZT high-resolution PET system in development at Stanford University. The modeling used GATE hits data and applied charge transport in the crystal and RC-CR processing of the simulated signals to model the electronics, including leading-edge discriminators and peak pick-off. Depth correction was also performed on the simulation data. Experimentally acquired data were used to determine energy resolution parameters and were compared to simulationdata. The distributions of the coincidence timing, anode energy, and cathode energy are consistent with experimental data. Numerically, the simulation achieved 153 ns FWHM coincidence time resolution (CTR), which is of the same order of magnitude as the raw 210 ns CTR previously found experimentally. Further, the anode energy resolution was found to be 5.9% FWHM (full width at half maximum) at 511 keV in the simulation, which is between the experimental value found for a single crystal of 3% and the value found for the dual-panel setup of 8.02%, after depth correction. Developing this advanced simulation improves upon the limitations of GATE for modeling semiconductor PET systems and provides a means for deeper analysis of the coincidence timing resolution and other complementary electron-hole dependent systemparameters.

A simulation study of the system characteristics for a long axial FOV PET design based on monolithic BGO flat panels compared with a pixelated LSO cylindrical design

BackgroundAlthough a new generation of tomographs with a longer axial field-of-view called total-body PET have been developed, they are not widely utilized due to their high cost compared to conventional scanners. The newly designed walk-through total-body PET scanner is introduced as a high-throughput and cost-efficient alternative to total-body PET scanners, by making use of a flat panel geometry and lower cost, depth-of-interaction capable, monolithic BGO detectors. The main aim of the presented study is to evaluate through Monte Carlo simulation the system characteristics of the walk-through total-body PET scanner by comparing it with a Quadra-like total-body PET of similar attributes to the Siemens Biograph Vision Quadra.MethodsThe walk-through total-body PET is comprised of two flat detector panels, spaced 50 cm apart. Each panel, 70 ×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} 106 cm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^2$$\\end{document} in size, consists of 280 BGO-based monolithic detectors. The Quadra-like TB-PET has been simulated based on the characteristics of the Biograph Vision Quadra, one of the most common total-body PET scanners with 106 cm of axial field-of-view, which is constructed with pixelated LSO scintillation crystals. The spatial resolution, sensitivity, count rate performance, scatter fractions, and image quality of both scanners are simulated in the GATE simulation toolkit for comparison.ResultsDue to the DOI-capable detectors used in the walk-through total-body PET, the values of the spatial resolution of this scanner were all below 2 mm along directions parallel to the panels, and reached a maximum of 3.36 mm in the direction perpendicular to the panels. This resolution is a large improvement compared to the values of the Quadra-like TB-PET. The walk-through total-body PET uses its maximum sensitivity (154 cps/kBq) for data acquisition and image reconstruction.ConclusionBased on the combination of very good spatial resolution and high sensitivity of the walk-through total-body PET, along with a 2.2 times lower scintillation crystal volume and 1.8 times lower SiPM surface, this scanner can be a very cost-efficient alternative for total-body PET scanners in cases where concomitant CT is not required.

Simulation of universal optical logic gates under energy sharing collisions of Manakov solitons and fulfillment of practical optical logic criteria.

The universal optical logic gates, namely, nand and nor gates, have been theoretically simulated by employing the energy sharing collision of bright optical solitons in the Manakov system, governing pulse propagation in a highly birefringent fiber. Further, we also realize the two-input optical logic gates, such as and, or, xor, xnor, for completeness of our scheme. Interestingly, our idea behind the simulation naturally satisfies all the criteria for practical optical logic, which in turn displays the strength and versatility of our theoretical simulation of universal optical logic gates. Hence, our approach paves the way for the experimentalists to create a new avenue in this direction if the energy sharing collisions of Manakov solitons are experimentally realized in the future.

MCGPU-PET: An open-source real-time Monte Carlo PET simulator

Monte Carlo (MC) simulations are commonly used to model the emission, transmission, and/or detection of radiation in Positron Emission Tomography (PET). In this work, we introduce a new open-source MC software for PET simulation, MCGPU-PET, which has been designed to fully exploit the computing capabilities of modern GPUs to simulate the acquisition of more than 100 million coincidences per second from voxelized sources and material distributions. The new simulator is an extension of the PENELOPE-based MCGPU code previously used in cone-beam CT and mammography applications. We validated the accuracy of the accelerated code by comparing it to GATE and PeneloPET simulations achieving an agreement within 10 percent approximately. As an example application of the code for fast estimation of PET coincidences, a scan of the NEMA IQ phantom was simulated. A fully 3D sinogram with 6382 million true coincidences and 731 million scatter coincidences was generated in 54 s in one GPU. MCGPU-PET provides an estimation of true and scatter coincidences and spurious background (for positron-gamma emitters such as 124I) at a rate 3 orders of magnitude faster than CPU-based MC simulators. This significant speed-up enables the use of the code for accurate scatter and prompt-gamma background estimations within an iterative image reconstruction process. Program SummaryProgram Title: MCGPU-PETCPC Library link to program files:https://doi.org/10.17632/k5x2bsf27m.2Licensing provisions: CC0 1.0Programming language: C (with NVIDIA CUDA extensions)Journal reference of the previous version: Badal A, Sharma D, Graff C G, Zeng R and Badano A, Mammography and breast tomosynthesis simulator for virtual clinical trials, Computer Physics Communications 261, 107,779 (2021); https://doi.org/10.1016/j.cpc.2020.107779Reasons for the new version: The open source x-ray imaging simulator MCGPU was modified to simulate Positron Emission Tomography (PET), extending the medical imaging applications that can be modeled with the system. The main radiation transport algorithm has not been changed, but new radiation source and detector models were implemented.Nature of problem: Due to their stochastic nature, MC methods require a large number of computations to obtain low-noise estimations, which makes them usually very time-consuming. This has limited their application in PET imaging to offline tasks where the simulation time is not a critical factor, leaving out other relevant cases that would benefit from accurate calculations.Solution method: The development of computers with multiple CPUs and GPUs for scientific computing has enabled tackling real-time MC simulations, i.e. performing simulations fast enough to obtain results at the same time as other processes of the imaging pipeline. We introduce a new open source software, MCGPU-PET, for simulating PET acquisitions with GPUs that simulates more than 100 million detected coincidences per second, which makes it even faster than many real PET acquisitions. The software samples gamma rays emitted from inside a voxelized anatomical model following a user input radiotracer distribution. The gamma ray coincidences arriving at the ideal ring detector are tallied in either a sinogram or list mode, and can be reconstructed using standard PET reconstruction algorithms.

Toward a Voltage Reconfigurable Logic Gate

Currently, novel approaches are being developed to overcome the imminent Moore's law failure. The techniques attempt to gain greater computing power by reducing the number of transistors. This work presents the simulation of a reconfigurable voltage logic gate based on the equation of a plane. The proposal is achieved by using two variables of the equation of a plane as inputs and the other as output. The proposed circuit can perform the NAND and NOR logic gates, known as universal logic gates. The simulation results show the feasibility of the proposed reconfigurable logic gate. Also, the presented circuit is compatible with the transistor-transistor-logic and can be modified to implement other logic gates by changing a voltage level.

AUTOMATIC FISHPOND IRRIGATION DOOR CONTROL SYSTEM BASED ON ATMEGA16 MICROCONTROLLER AND SMS GATEWAY

The process of controlling irrigation doors in fishponds is still mostly done manually, this results in the performance of farmers being less effective and efficient. Current technological developments, especially in the field of IoT, can be used to design a simulation that is able to control irrigation gates automatically. Based on the results of the tests that have been carried out, it can be concluded that the ATmega16-based automatic irrigation gate simulation tool can work well according to the designed working principle. If the condition of fishpond water is less than the ideal height of the fishpond and the condition of river water is more than the height of the fishpond, the motor will move to "open" the irrigation door to fill fishpond water. If the fishpond water condition is more than the ideal height and the river water condition is less than the fishpond height, the motor will move to "open" the irrigation door to discharge fishpond water and if the river water condition is the same as the fishpond water condition, the motor will move "close” the irrigation door so that the ideal height of the fishpond can be achieved. There are certain conditions to control the door manually using the SMS Gateway. Information about the maximum or minimum fishpond water level will be displayed on the LCD to determine the maximum or minimum fishpond height using Keypad.

Monte Carlo Dosimetry Validation for X-Ray Guided Endovascular Procedures

Endovascular treatment is continuously gaining ground in vascular surgery procedures. However, current patient radiation dose estimation does not take into account the exact patient morphology and organs' composition. Monte Carlo (MC) simulation can accurately estimate the dose by recreating the irradiation process generated during X-ray-guided interventions. This study aimed to validate the MC simulation models by comparing simulated and measured dose distributions in endovascular aortic aneurysm repair (EVAR) procedures. We conducted a clinical study in patients treated for EVAR. Patient dose measurements were taken with passive dosimeters using Optically Stimulated Luminescence technology in 4 specific anatomical points on the skin: xiphoid process, pubic symphysis, right and left iliac crest. Dose measurements were compared to the corresponding simulated doses with the Geant4 Application for Emission Tomography (GATE) and GPU Geant4-based Monte Carlo Simulations (GGEMS) MC simulations softwares. The MC simulation took as input the computed tomography scan of the patient and the parameters of the imaging system (orientation angles, tube voltage, and aluminum filtration) and gives as output the three-dimensional (3D) dose map for each patient and angulation. A good agreement with real doses was found for doses simulated by the MC GATE method (P<0.0001; r=0.97; 95% confidence interval [CI] [0.96-0.98]), as well as for doses simulated by the GGEMS method (P<0.0001; r=0.96; 95% CI [0.94-0.97]). The mean relative error for all measurements was 5±5% in the MC GATE group and 6±5% in the GGEMS group. Process execution on GGEMS (6sec) was faster than the GATE MC simulation (5hr). Considering the current imaging settings, this study shows the potential of using the GATE and GGEMS MC simulations platforms to model the 3D dose distributions during EVAR procedures.

Dosimetric Evaluation of 177Lu Peptide Receptor Radionuclide Therapy Using GATE and Planet Dose

This study aimed to compare the commercial dosimetric software Planet® Dose (version 3.1.1) from DOSIsoft and the open-source toolkit GATE. Dosimetry was performed for six patients receiving 200 mCi of Lutathera® every 8 weeks for four treatment cycles. For the dose calculation with Planet®, SPECT/CT images were acquired at 4, 24, 72 and 192 h post-injection. After the registration of all the time points to T0, the organs of interest (OOIs) were segmented. Time-activity curves were produced and the absorbed dose was calculated using the bi- and tri-exponential fitting methods. Regarding GATE simulations, the SPECT images of the 24 h time point were utilized for the radiopharmaceutical biodistribution in the OOIs and the attenuation maps were produced using the CT images. For liver and spleen, the average relative difference between GATE and Planet® was 9.6% and 11.1% for biexponential and 12.4% and 30.5% for triexponential fitting, respectively. The right and left kidneys showed differences up to 10.7% and 10.4% for the biexponential and up to 60.6% and 11.9% for the triexponential model, respectively. The absorbed dose calculated with GATE, Planet®(bi-exp) and Planet®(tri-exp) was in agreement with the literature. The results of the bi-exponential fitting were similar to the GATE-resulted calculations, while the tri-exponential fitting had a higher relative difference.

A GATE simulation study for dosimetry in cancer cell and micrometastasis from the 225Ac decay chain

BackgroundRadiopharmaceutical therapy (RPT) with alpha-emitting radionuclides has shown great promise in treating metastatic cancers. The successive emission of four alpha particles in the 225Ac decay chain leads to highly targeted and effective cancer cell death. Quantifying cellular dosimetry for 225Ac RPT is essential for predicting cell survival and therapeutic success. However, the leading assumption that all 225Ac progeny remain localized at their target sites likely overestimates the absorbed dose to cancer cells. To address limitations in existing semi-analytic approaches, this work evaluates S-values for 225Ac’s progeny radionuclides with GATE Monte Carlo simulations.MethodsThe cellular geometries considered were an individual cell (10 µm diameter with a nucleus of 8 µm diameter) and a cluster of cells (micrometastasis) with radionuclides localized in four subcellular regions: cell membrane, cytoplasm, nucleus, or whole cell. The absorbed dose to the cell nucleus was scored, and self- and cross-dose S-values were derived. We also evaluated the total absorbed dose with various degrees of radiopharmaceutical internalization and retention of the progeny radionuclides 221Fr (t1/2 = 4.80 m) and 213Bi (t1/2 = 45.6 m).ResultsFor the cumulative 225Ac decay chain, our self- and cross-dose nuclear S-values were both in good agreement with S-values published by MIRDcell, with per cent differences ranging from − 2.7 to − 8.7% for the various radionuclide source locations. Source location had greater effects on self-dose S-values than the intercellular cross-dose S-values. Cumulative 225Ac decay chain self-dose S-values increased from 0.167 to 0.364 GyBq−1 s−1 with radionuclide internalization from the cell surface into the cell. When progeny migration from the target site was modelled, the cumulative self-dose S-values to the cell nucleus decreased by up to 71% and 21% for 221Fr and 213Bi retention, respectively.ConclusionsOur GATE Monte Carlo simulations resulted in cellular S-values in agreement with existing MIRD S-values for the alpha-emitting radionuclides in the 225Ac decay chain. To obtain accurate absorbed dose estimates in 225Ac studies, accurate understanding of daughter migration is critical for optimized injected activities. Future work will investigate other novel preclinical alpha-emitting radionuclides to evaluate therapeutic potency and explore realistic cellular geometries corresponding to targeted cancer cell lines.

Synthesis and characterization of Ce3+-doped barium-gadolinium-fluoroborate glasses for proton beam diagnostic

By using a melt-quenching technique in an air atmosphere, barium-gadolinium-fluoroborate scintillating glasses with different concentrations of BaO and CeF3 were fabricated. The purpose of developing glasses is to be applied as proton or x-ray energy detectors for medical purposes. Physical and scintillating properties of the fabricated glasses were tested and analyzed, including glass density and spectroscopic properties such as transmittance, photoluminescence, x-ray absorption near edge structure, and x-ray-induced luminescence. Moreover, the glasses were impinged by a 70 MeV proton beam at the Proton Center of King Chulalongkorn Memorial Hospital to observe their proton-induced light emission. The absorption edge of the transmittance revealed that the glasses showed a redshift at high concentrations of BaO and CeF3. The glasses had a broad emission band centering around 400 nm due to the 5d–4f transition of Ce3+ induced by x-ray. The higher light yield was observed at a higher cerium compound glass. Our glass can clearly measure the depth-dose profile of the impinging proton beam by varying different water thicknesses. Moreover, the depth-dose profile results are in good agreement with that of the energy deposition of proton beams in glass calculated via GATE simulation.

Numerical Model for 32-Bit Magnonic Ripple Carry Adder

In CMOS-based electronics, the most straightforward way to implement a summation operation is to use the ripple carry adder (RCA). Magnonics, the field of science concerned with data processing by spin-waves and their quanta magnons, recently proposed a magnonic half-adder that can be considered as the simplest magnonic integrated circuit. Here, we develop a computation model for the magnonic basic blocks to enable the design and simulation of magnonic gates and magnonic circuits of arbitrary complexity and demonstrate its functionality on the example of a 32-bit integrated RCA. It is shown that the RCA requires the utilization of additional regenerators based on magnonic directional couplers with embedded amplifiers to normalize the magnon signals in-between the half-adders. The benchmarking of large-scale magnonic integrated circuits is performed. The energy consumption of 30 nm-based magnonic 32-bit adder can be as low as 961aJ per operation with taking into account all required amplifiers.

Evaluation in Terms of Dosimetry and Fertility of F18-FDG and Ga68- PSMA in Prostate Cancer Imaging: A Simulation with GATE.

F18 and Ga68 radioisotopes are used in PET imaging for prostate cancer. It was aimed to calculate the prostate, testicle and bladder effective doses (ED) caused by F18 and Ga68 used in prostate cancer imaging with PET/CT via simulation with the GATE toolkit and evaluate the ED in terms of fertility. The prostate, testicle and bladder were defined together with their geometric properties and densities in GATE simulation. F18 and Ga68 with activity of 277.5 MBq and 151.7 MBq were identified in the prostate as a source organ. The ED, uncertainties, and S values were taken as an output file in the TXT format with the DoseActors command. S values were used for validation of the simulation. The ED of the prostate, total testicle and bladder for F18 were found to be 6.627E-04 ± 1.799E-06, 12.74E-07 ± 4.11E-08 and 1.617E-05 ± 4.317E-09 (Gy/s), respectively. The ED of the prostate, total testicle, and bladder for Ga68 were found to be 9.195E-04 ± 2.660E-06, 6.54E-07 ± 2.93E-08 and 4.290E-05 ± 6.936E-09 (Gy/s), respectively. It was found that Ga68 produced high prostate and bladder ED, and F18 produced high testicular ED. In terms of male fertility, Ga68 seems to be a good alternative because it produces low testicular doses. The ED of the testicle both F18 and Ga68 were below the reported spermatogonia and azoospermia dose.

Fast scintillating Ce3+ doped gadolinium aluminum fluoroborate glass for calorimetry in proton CT prototype: A preliminary work

In this work, Ce3+-doped gadolinium aluminum fluoroborate glass scintillators, 25Gd2O3-(65-x)B2O3–10AlF3-xCeF3, where, x = 0, 0.05, 0.1, 0.2, and, 0.3 mol%, were prepared and studied systematically for developing a proton calorimeter used in proton-computed tomography. Various properties of the prepared glass scintillators were evaluated through density, X-ray absorption near edge spectroscopy, transmittance, photoluminescence, decay time, X-ray-induced luminescence, and proton-induced luminescence measurements. The highest density of the fabricated glass scintillators reached 4.31 g/cm3. The X-ray-induced luminescence showed a broad emission band centered at approximately 400 nm, and the decay time was less than 30 ns. The glass scintillators were irradiated by a proton beam with a beam energy of 100–115 MeV. It was found that the glass scintillators emitted light at almost the same wavelength as that of the X-ray-induced luminescence. Moreover, the energy deposition inside the fabricated glass scintillators was simulated using GATE simulation and compared with the results obtained for proton-induced luminescence. The energy deposition obtained from the simulation showed the same trend as that for the fraction of light emitted from the proton irradiation measurement. Therefore, these fabricated glass scintillators can be used as calorimeter in medical physics and other applications related to proton or X-ray irradiation.

2D-dwell-time analysis with simulations of ion-channel gating using high-performance computing

Single-channel patch-clamp recordings allow observing the action of a single protein complex in real time and hence the deduction of the underlying conformational changes in the ion-channel protein. Commonly, recordings are modeled using hidden Markov chains, connecting open and closed states in the experimental data with protein conformations. The rates between states denote transition probabilities that could be modified by membrane voltage or ligand binding. Modeling algorithms have to deal with limited recording bandwidth and a very noisy background. It was previously shown that the fit of two-dimensional (2D)-dwell-time histograms with simulations is very robust in that regard. Errors introduced by the low-pass filter or noise cancel out to a certain degree when comparing experimental and simulated data. In addition, the topology of models (that is, the chain of open and closed states) could be inferred from 2D-histograms. However, the 2D-fit was never applied to its full potential. A major reason may be the extremely time-consuming and often unreliable fitting process, due to the stochastic variability in the simulations. We have now solved these issues by introducing a message-passing interface (MPI) allowing massive parallel computing on a high-performance computing (HPC) cluster and obtaining ensemble solutions. With ensembles, we have demonstrated how important ranked solutions are for difficult tasks related to a noisy background, fast gating events beyond the corner frequency of the low-pass filter, and topology estimation of the underlying Markov model. Finally, we have shown that, by combining the objective function of the 2D-fit with the deviation of the current amplitude distributions, automatic determination of the current level of the conducting state is possible, even with an apparent current reduction due to low-pass filtering. Making use of an HPC cluster, the power of 2D-dwell-time analysis can be used to its fullest with minor input of the experimenter.

3D printed 2D range modulators preserve radiation quality on a microdosimetric scale in proton and carbon ion beams

IntroductionParticle therapy using pencil beam scanning (PBS) faces large uncertain- ties related to ranges and target motion. One possibility to improve existing mitigation strategies is a 2D range modulator (2DRM). A 2DRM offers faster irradiation times by reducing the number of layers and spots needed to create a spread-out Bragg peak. We have investigated the impact of 2DRM on microdosimetric spectra measured in proton and carbon ion beams. Materials and MethodsTwo 2DRMs were designed and 3D printed, one for.124.7 MeV protons and one for 238.6 MeV/u carbon ions. Their dosimetric validation was performed using Roos and PinPoint ionization chamber and EBT3 films. Monte Carlo simulations were done using GATE. A silicon-based solid-state microdosimeter was used to collect pulse-height spectra along three depths for two irradiation modalities, PBS and a single central beam. ResultsFor both particle types, the original pin design had to be optimized via GATE simulations. The difference between the R80 of the simulated and measured depth dose curve was 0.1 mm. The microdosimetric spectra collected with the two irradiation modalities overlap well. Their mean lineal energy values differ over all positions by 5.2 % for the proton 2DRM and 2.1 % for the carbon ion 2DRM. ConclusionRadiation quality in terms of lineal energy was independent of the irradiation method. This supports the current approach in reference dosimetry, where the residual range is chosen as a beam quality index to select stopping power ratios.

Physiological role of SK channels in modulating cardiac repolarization: APD and dispersion at slow heart rate in long QT syndrome.

Long QT syndrome (LQTS) is a congenital disease associated with polymorphic ventricular tachycardia (pVT) and sudden cardiac death. The hallmarks of LQTS are early afterdepolarizations that initiate pVT and dispersion of repolarization allowing reentry formation. Small conductance Ca2+-activated K+ (SK) channels are directly gated by Ca2+ and provide feedback from Ca2+ to membrane voltage to accelerate cardiac repolarization, which may help normalizing LQTS. Using optical mapping, we examined the role of ISK in transgenic rabbit models of LQT1, LQT2, and LQT5 and found that enhancing ISK with NS309 consistently shortened APD, reduced APD dispersion, and suppressed pVT genesis universally in the three LQT rabbit models. Enhancement of ISK has a greater impact at longer cycle length, flattening restitution curves at slow heart rate where most pVTs occur in LQTS. We incorporated a six state ISK gating simulation combined with intrinsic rectification and divalent block into the Mahajan rabbit action potential model to investigate the role of ISK in suppressing LQT-related arrhythmias. Increasing levels of SK channel conductance (gSK) were able to shorten and reduce APD dispersion simulated by conductance gradients of gKs by ∼64% under LQT2 conditions and gtof by ∼70% in LQT1 conditions. Computer modeling indicates that ISK can reduce APD dispersion through two mechanisms; increased Ca2+ duration in the prolonged APD cells augment ISK to shorten long APD and lowering plateau Vm by ISK masks IKs heterogeneity by reducing IKs's role in repolarization. In conclusion, the Ca2+-dependent gating of ISK allows it to directly feedback on the APD especially when other K+ channels are not functional and to be a potential therapeutic target for LQTS.

Design and simulation of all-optical majority gates using fluid infiltration approach in photonic crystal slab

Design and simulation of all-optical majority gates using fluid infiltration approach in photonic crystal slab

Design and simulation of an all-optical Fredkin gate based on silicon slab-waveguide in a 2-D photonic crystal

Design and simulation of an all-optical Fredkin gate based on silicon slab-waveguide in a 2-D photonic crystal