Experimental, analytical, and computational investigation of mesh grid thermal physics in an electron gun with dispenser cathode.

Gridded electron guns are key components of various electron beam based vacuum tubes. Mesh grids may be utilized for electron beam extraction and control. As part of the electron beam may be intercepted by the mesh grid, heating occurs, which could translate into performance degradation of the vacuum tube or even failure. This paper introduces an analytical model based on first physics principles for mesh grid heating in an electron gun, toward generating the upper bound for the intercepted electron beam power. 3D simulations and exploratory experiments for mesh grid heating in an electron gun directionally confirm the predictions of the analytical model. This analytical approach may be leveraged further when the upper bounds of mesh grid heating in electron guns are needed, as well as for adjusting mesh grid topology to increase its robustness against electron beam heating.

Design, characterization and experimental validation of a compact, flexible pulsed power architecture for ex vivo platelet activation.

Electric pulses can induce various changes in cell dynamics and properties depending upon pulse parameters; however, pulsed power generators for in vitro and ex vivo applications may have little to no flexibility in changing the pulse duration, rise- and fall-times, or pulse shape. We outline a compact pulsed power architecture that operates from hundreds of nanoseconds (with the potential for modification to tens of nanoseconds) to tens of microseconds by modifying a Marx topology via controlling switch sequences and voltages into each capacitor stage. We demonstrate that this device can deliver pulses to both low conductivity buffers, like standard pulsed power supplies used for electroporation, and higher conductivity solutions, such as blood and platelet rich plasma. We further test the effectiveness of this pulse generator for biomedical applications by successfully activating platelets ex vivo with 400 ns and 600 ns electric pulses. This novel bioelectrics platform may provide researchers with unprecedented flexibility to explore a wide range of pulse parameters that may induce phenomena ranging from intracellular to plasma membrane manipulation.

Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

BACKGROUND: Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. AIMS: To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. METHODS: PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. RESULTS: PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet-derived microparticles, platelets, and platelet aggregates whereas SMHEF pulses primarily resulted in platelet-derived microparticles. Microparticles and platelets in PRP activated with SMLEF bipolar pulses had significantly lower annexin V-positivity than those following SMHEF activation. In contrast, the % P-selectin positivity and surface P-selectin expression (MFI) for platelets and microparticles in SMLEF bipolar pulse activated PRP was significantly higher than that in SMHEF-activated PRP, but not significantly different from that produced by thrombin activation. Higher levels of EGF were observed following either SMLEF bipolar pulses or SMHEF pulses of PRP than after bovine thrombin activation while VEGF, PDGF, and PF4 levels were similar with all three activating conditions. Cell proliferation was significantly increased by releasates of both SMLEF bipolar pulse and SMHEF pulse activated PRP compared to plasma alone. CONCLUSIONS: PEF activation of PRP at bipolar low vs. monopolar high field strength results in differential platelet-derived microparticle production and activation of platelet surface procoagulant markers while inducing similar release of growth factors and similar capacity to induce cell proliferation. Stimulation of PRP with SMLEF bipolar pulses is gentler than SMHEF pulses, resulting in less platelet microparticle generation but with overall activation levels similar to that obtained with thrombin. These results suggest that PEF provides the means to alter, in a controlled fashion, PRP properties thereby enabling evaluation of their effects on wound healing and clinical outcomes.

Multisource inverse-geometry CT. Part II. X-ray source design and prototype.

PURPOSE: This paper summarizes the development of a high-power distributed x-ray source, or "multisource," designed for inverse-geometry computed tomography (CT) applications [see B. De Man et al., "Multisource inverse-geometry CT. Part I. System concept and development," Med. Phys. 43, 4607-4616 (2016)]. The paper presents the evolution of the source architecture, component design (anode, emitter, beam optics, control electronics, high voltage insulator), and experimental validation. METHODS: Dispenser cathode emitters were chosen as electron sources. A modular design was adopted, with eight electron emitters (two rows of four emitters) per module, wherein tungsten targets were brazed onto copper anode blocks-one anode block per module. A specialized ceramic connector provided high voltage standoff capability and cooling oil flow to the anode. A matrix topology and low-noise electronic controls provided switching of the emitters. RESULTS: Four modules (32 x-ray sources in two rows of 16) have been successfully integrated into a single vacuum vessel and operated on an inverse-geometry computed tomography system. Dispenser cathodes provided high beam current (>1000 mA) in pulse mode, and the electrostatic lenses focused the current beam to a small optical focal spot size (0.5 × 1.4 mm). Controlled emitter grid voltage allowed the beam current to be varied for each source, providing the ability to modulate beam current across the fan of the x-ray beam, denoted as a virtual bowtie filter. The custom designed controls achieved x-ray source switching in <1 µs. The cathode-grounded source was operated successfully up to 120 kV. CONCLUSIONS: A high-power, distributed x-ray source for inverse-geometry CT applications was successfully designed, fabricated, and operated. Future embodiments may increase the number of spots and utilize fast read out detectors to increase the x-ray flux magnitude further, while still staying within the stationary target inherent thermal limitations.

Platelet activation using electric pulse stimulation: growth factor profile and clinical implications.

BACKGROUND: Autologous platelet gel therapy using platelet-rich plasma has emerged as a promising alternative for chronic wound healing, hemostasis, and wound infection control. A critical step for this therapeutic approach is platelet activation, typically performed using bovine thrombin (BT) and calcium chloride. However, exposure of humans to BT can stimulate antibody formation, potentially resulting in severe hemorrhagic or thrombotic complications. Electric pulse stimulation using nanosecond PEFs (pulse electric fields) is an alternative, nonbiochemical platelet activation method, thereby avoiding exposure to xenogeneic thrombin and associated risks. METHODS: In this study, we identified specific requirements for a clinically relevant activator instrument by dynamically measuring current, voltage, and electric impedance for platelet-rich plasma samples. From these samples, we investigated the profile of growth factors released from human platelets with electric pulse stimulation versus BT, specifically platelet-derived growth factor, transforming growth factor ß, and epidermal growth factor, using commercial enzyme-linked immunosorbent assay kits. RESULTS: Electric pulse stimulation triggers growth factor release from platelet α-granules at the same or higher level compared with BT. CONCLUSION: Electric pulse stimulation is a fast, inexpensive, easy-to-use platelet activation method for autologous platelet gel therapy.

Design and characterization of electron beam focusing for X-ray generation in novel medical imaging architecture.

A novel electron beam focusing scheme for medical X-ray sources is described in this paper. Most vacuum based medical X-ray sources today employ a tungsten filament operated in temperature limited regime, with electrostatic focusing tabs for limited range beam optics. This paper presents the electron beam optics designed for the first distributed X-ray source in the world for Computed Tomography (CT) applications. This distributed source includes 32 electron beamlets in a common vacuum chamber, with 32 circular dispenser cathodes operated in space charge limited regime, where the initial circular beam is transformed into an elliptical beam before being collected at the anode. The electron beam optics designed and validated here are at the heart of the first Inverse Geometry CT system, with potential benefits in terms of improved image quality and dramatic X-ray dose reduction for the patient.

A multi-source inverse-geometry CT system: initial results with an 8 spot x-ray source array.

We present initial experimental results of a rotating-gantry multi-source inverse-geometry CT (MS-IGCT) system. The MS-IGCT system was built with a single module of 2 × 4 x-ray sources and a 2D detector array. It produced a 75 mm in-plane field-of-view (FOV) with 160 mm axial coverage in a single gantry rotation. To evaluate system performance, a 2.5 inch diameter uniform PMMA cylinder phantom, a 200 µm diameter tungsten wire, and a euthanized rat were scanned. Each scan acquired 125 views per source and the gantry rotation time was 1 s per revolution. Geometric calibration was performed using a bead phantom. The scanning parameters were 80 kVp, 125 mA, and 5.4 µs pulse per source location per view. A data normalization technique was applied to the acquired projection data, and beam hardening and spectral nonlinearities of each detector channel were corrected. For image reconstruction, the projection data of each source row were rebinned into a full cone beam data set, and the FDK algorithm was used. The reconstructed volumes from upper and lower source rows shared an overlap volume which was combined in image space. The images of the uniform PMMA cylinder phantom showed good uniformity and no apparent artifacts. The measured in-plane MTF showed 13 lp cm(-1) at 10% cutoff, in good agreement with expectations. The rat data were also reconstructed reliably. The initial experimental results from this rotating-gantry MS-IGCT system demonstrated its ability to image a complex anatomical object without any significant image artifacts and to achieve high image resolution and large axial coverage in a single gantry rotation.