Antonio Caiafa

High Power Distributed X-ray Source

This paper summarizes the development of a distributed x-ray source with up to 60kW demonstrated instantaneous power. Component integration and test results are shown for the dispenser cathode electron gun, fast switching controls, high voltage stand-off insulator, brazed anode, and vacuum system. The current multisource prototype has been operated for over 100 hours without failure, and additional testing is needed to discover the limiting component. Example focal spot measurements and x-ray radiographs are included. Lastly, future development opportunities are highlighted.

X-ray Multisource for Medical Imaging

This paper presents a progress update with the development of a distributed x-ray source. We present a high level summary of the source integration, simulation and experimental results, as well as challenges in electron beam focusing, beam current gating, voltage isolation, and anode technologies. We present focal spot measurements, x-ray images and a summary of our distributed x-ray source concept.

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 &bgr;, and epidermal growth factor, using commercial enzyme-linked immunosorbent assay kits. RESULTS Electric pulse stimulation triggers growth factor release from platelet &agr;-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.

Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation

Abstract Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEFs inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

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 X-Ray and CT: Lessons Learned and Future Outlook

Distributed X-ray sources open the way to innovative system concepts in X-ray and computed tomography. They offer promising opportunities in terms of system performance, but they pose unique challenges in terms of source and system technologies. Several academic and industrial teams have proposed a variety of concepts and developed some unique prototypes. We present a broad review of multisource systems. We also discuss X-ray source components and challenges. We close with our perspective on the future prospects of multisource imaging.

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.

Multi-source inverse-geometry CT: From system concept to research prototype

Third-generation CT architectures are approaching fundamental limits. Dose-efficiency is limited by finite detector efficiency and by limited control over the X-ray flux spatial profile. Increasing the volumetric coverage comes with increased scattered radiation, cone-beam artifacts, Heel effect, wasted dose and cost. Spatial resolution is limited by focal spot size and detector cell size. Temporal resolution is limited by mechanical constraints, and alternative geometries such as electron-beam CT and dual-source CT come with severe tradeoffs in terms of image quality, dose-efficiency and complexity. The concept of multi-source inverse-geometry CT (IGCT) breaks through several of the above limitations [1-3], promising a low-dose high image quality volumetric CT architecture. In this paper, we present recent progress with the design and integration efforts of the first gantry-based multi-source CT scanner.

Multisource inverse-geometry CT — Prototype system integration

Todays 3rd generation CT scanners have one or two X-ray tubes, with one focal spot or “source” per vacuum chamber or “tube”. Our first multi-source inverse geometry CT prototype has eight X-ray sources. We have demonstrated multisource imaging with an 8-spot X-ray tube on a stationary gantry and a rotating phantom. We present an update on the development of the gantry-based multi-source CT scanner: we combine the multi-source X-ray tube and gantry rotation producing the first multi-source gantry-based CT scanner prototype. Currently the system is in the process of being upgraded to 32 X-ray sources to provide a larger field-of-view and to demonstrate the concept of virtual bowtie.

Initial results with a multisource inverse-geometry CT system

The multi-source inverse-geometry CT(MS-IGCT) system is composed of multiple sources and a small 2D detector array. An experimental MS-IGCT system was built and we report initial results with 2×4 x-ray sources, a 75 mm inplane field-of-view (FOV) and 160 mm z-coverage in a single gantry rotation. To evaluate the system performance, experimental data were acquired from several phantoms and a post-mortem rat. Before image reconstruction, geometric calibration, data normalization, beam hardening correction and detector spectral calibration were performed. For reconstruction, the projection data were rebinned into two full cone beam data sets, and the FDK algorithm was used. The reconstructed volumes from the upper and lower source rows shared an overlap volume which was combined in image space. The reconstructed images of the uniform cylinder phantom showed good uniformity of the reconstructed values without any artifacts. 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 ultimately achieve large volumetric coverage in a single gantry rotation.