Characterization of polycrystalline lead oxide for application in direct conversion X-ray detectors.

While polycrystalline lead oxide (poly-PbO) is known to be one of the most promising photoconductors for utilization in X-ray detectors, its major performance parameters such as charge yield and mobility-lifetime product (µτ) are still not well established and require further investigation. Combining the conventional X-ray induced photocurrent and pulse height spectroscopy techniques we examine the X-ray photogeneration and recombination processes in poly-PbO. The measurements indicate that the amount of energy required to release a single electron hole pair W ± (inverse of charge yield) strongly depends on applied electric field and at 10 V/µm reaches ~20 eV/ehp. Fitting the measured pulse height spectra with the Hecht formula provided µτ for holes and electrons to be 4.1 × 10-8 cm2/V and 10-9 cm2/V, respectively. Obtained µτ values combined with recently reported mobility values of charge carriers in PbO suggest a new direction towards improvement of PbO technology by incorporation of Frisch grid or X-ray transistor architectures.

Scintillator high-gain avalanche rushing photoconductor active-matrix flat panel imager: zero-spatial frequency x-ray imaging properties of the solid-state SHARP sensor structure.

PURPOSE: The authors are investigating the feasibility of a new type of solid-state x-ray imaging sensor with programmable avalanche gain: scintillator high-gain avalanche rushing photoconductor active matrix flat panel imager (SHARP-AMFPI). The purpose of the present work is to investigate the inherent x-ray detection properties of SHARP and demonstrate its wide dynamic range through programmable gain. METHODS: A distributed resistive layer (DRL) was developed to maintain stable avalanche gain operation in a solid-state HARP. The signal and noise properties of the HARP-DRL for optical photon detection were investigated as a function of avalanche gain both theoretically and experimentally, and the results were compared with HARP tube (with electron beam readout) used in previous investigations of zero spatial frequency performance of SHARP. For this new investigation, a solid-state SHARP x-ray image sensor was formed by direct optical coupling of the HARP-DRL with a structured cesium iodide (CsI) scintillator. The x-ray sensitivity of this sensor was measured as a function of avalanche gain and the results were compared with the sensitivity of HARP-DRL measured optically. The dynamic range of HARP-DRL with variable avalanche gain was investigated for the entire exposure range encountered in radiography∕fluoroscopy (R∕F) applications. RESULTS: The signal from HARP-DRL as a function of electric field showed stable avalanche gain, and the noise associated with the avalanche process agrees well with theory and previous measurements from a HARP tube. This result indicates that when coupled with CsI for x-ray detection, the additional noise associated with avalanche gain in HARP-DRL is negligible. The x-ray sensitivity measurements using the SHARP sensor produced identical avalanche gain dependence on electric field as the optical measurements with HARP-DRL. Adjusting the avalanche multiplication gain in HARP-DRL enabled a very wide dynamic range which encompassed all clinically relevant medical x-ray exposures. CONCLUSIONS: This work demonstrates that the HARP-DRL sensor enables the practical implementation of a SHARP solid-state x-ray sensor capable of quantum noise limited operation throughout the entire range of clinically relevant x-ray exposures. This is an important step toward the realization of a SHARP-AMFPI x-ray flat-panel imager.

Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion.

AIMS: To investigate the effects of the second generation antipsychotic (R/S)-amisulpride, and the chirally purified enantiomers, on glucose homeostasis in diet-induced obese (DIO) mice. METHODS: Normal and DIO mice were treated with pharmacologically relevant doses of amisulpride prior to oral glucose tolerance tests (OGTTs). Blood glucose, insulin, glucagon-like peptide-1, prolactin and amisulpride drug levels were determined. RESULTS: Racemic amisulpride significantly reduced glucose excursions during OGTT in both normal and DIO mice. This potent effect was preserved with the 'off-isomer', R-amisulpride (ED(50) 1 mg/kg). Insulin secretion was significantly increased with R-amisulpride with only a minor increase in prolactin levels. CONCLUSIONS: Amisulpride has antidiabetic actions in DIO mice resulting from increased insulin secretion. This provides some explanation for why amisulpride, unlike other atypical antipsychotics, is not diabetogenic in man. Furthermore, the observation that R-amisulpride is also antidiabetic and has minimal impact on prolactin levels presents the opportunity for development of this isomer as an antidiabetic agent.

A solid-state amorphous selenium avalanche technology for low photon flux imaging applications.

PURPOSE: The feasibility of a practical solid-state technology for low photon flux imaging applications was investigated. The technology is based on an amorphous selenium photoreceptor with a voltage-controlled avalanche multiplication gain. If this photoreceptor can provide sufficient internal gain, it will be useful for an extensive range of diagnostic imaging systems. METHODS: The avalanche photoreceptor under investigation is referred to as HARP-DRL. This is a novel concept in which a high-gain avalanche rushing photoconductor (HARP) is integrated with a distributed resistance layer (DRL) and sandwiched between two electrodes. The avalanche gain and leakage current characteristics of this photoreceptor were measured. RESULTS: HARP-DRL has been found to sustain very high electric field strengths without electrical breakdown. It has shown avalanche multiplication gains as high as 10(4) and a very low leakage current (< or = 20 pA/mm2). CONCLUSIONS: This is the first experimental demonstration of a solid-state amorphous photoreceptor which provides sufficient internal avalanche gain for photon counting and photon starved imaging applications.

Effect of repeated x-ray exposure on the resolution of amorphous selenium based x-ray imagers.

PURPOSE: A numerical model and the experimental methods to study the x-ray exposure dependent change in the modulation transfer function (MTF) of amorphous selenium (a-Se) based active matrix flat panel imagers (AMFPIs) are described. The physical mechanisms responsible for the x-ray exposure dependent change in MTF are also investigated. METHODS: A numerical model for describing the x-ray exposure dependent MTF of a-Se based AMFPIs has been developed. The x-ray sensitivity and MTF of an a-Se AMFPI have been measured as a function of exposure. The instantaneous electric field and free and trapped carrier distributions in the photoconductor layer are obtained by numerically solving the Poisson's equation, continuity equations, and trapping rate equations using the backward Euler finite difference method. From the trapped carrier distributions, a method for calculating the MTF due to incomplete charge collection is proposed. RESULTS: The model developed in this work and the experimental data show a reasonably good agreement. The model is able to simultaneously predict the dependence of the sensitivity and MTF on accumulated exposure at different applied fields and bias polarities, with the same charge transport parameters that are typical of the particular a-Se photoconductive layer that is used in these AMFPIs. Under negative bias, the MTF actually improves with the accumulated x-ray exposure while the sensitivity decreases. The MTF enhancement with exposure decreases with increasing applied field. CONCLUSIONS: The most prevalent processes that control the MTF under negative bias are the recombination of drifting holes with previously trapped electrons (electrons remain in deep traps due to their long release times compared with the time scale of the experiments) and the deep trapping of drifting holes and electrons.

Performance of a static-anode/flat-panel x-ray fluoroscopy system in a diagnostic strength magnetic field: a truly hybrid x-ray/MR imaging system.

Minimally invasive procedures are increasing in variety and frequency, facilitated by advances in imaging technology. Our hybrid imaging system (GE Apollo flat panel, custom Brand x-ray static anode x-ray tube, GE Lunar high-frequency power supply and 0.5 T Signa SP) provides both x-ray and MR imaging capability to guide complex procedures without requiring motion of the patient between two distant gantries. The performance of the x-ray tube in this closely integrated system was evaluated by modeling and measuring both the response of the filament to an externally applied field and the behavior of the electron beam for field strengths and geometries of interest. The performance of the detector was assessed by measuring the slanted-edge modulation transfer function (MTF) and when placed at zero field and at 0.5 T. Measured resonant frequencies of filaments can be approximated using a modified vibrating beam model, and were at frequencies well below the 25 kHz frequency of our generator for our filament geometry. The amplitude of vibration was not sufficient to cause shorting of the filament during operation within the magnetic field. A simple model of electrons in uniform electric and magnetic fields can be used to estimate the deflection of the electron beam on the anode for the fields of interest between 0.2 and 0.5 T. The MTF measured at the detector and the DQE showed no significant difference inside and outside of the magnetic field. With the proper modifications, an x-ray system can be fully integrated with a MR system, with minimal loss of image quality. Any x-ray tube can be assessed for compatibility when placed at a particular location within the field using the models. We have also concluded that a-Si electronics are robust against magnetic fields. Detailed knowledge of the x-ray system installation is required to provide estimates of system operation.

Ghosting caused by bulk charge trapping in direct conversion flat-panel detectors using amorphous selenium.

Direct flat-panel detectors using amorphous selenium (a-Se) x-ray photoconductors are gaining wide-spread clinical use. The goal of our investigation is to understand the physical mechanisms responsible for ghosting, i.e., x-ray induced change in sensitivity that results in image persistence, so that the knowledge can be used to consistently minimize ghosting artifacts in a-Se flat-panel detectors. In this paper we will discuss the effect on x-ray sensitivity of charge trapping in a-Se, which is the dominant source for ghosting in a-Se flat-panel detectors. Our approach is to correlate ghosting in electroded a-Se detectors with the trapped charge concentration measured by the "time-of-flight" (TOF) method. All measurements were performed as a function of radiation exposure X of up to approximately 20 R at electric field strength's of E(Se)=5 and 10 V/microm. The results showed that the x-ray sensitivity decreased as a function of X and the amount of ghosting decreased with increasing E(Se). The shape of the TOF curves changed as a result of irradiation in a manner indicating trapped electrons in the bulk of a-Se. The density of trapped electrons n(t) increases as a function of X. A method was developed to determine the values of n(t) in the bulk of a-Se from the TOF measurements, and to predict the corresponding change in x-ray sensitivity. Our results showed that a recombination coefficient consistent with that predicted by Langevin produced good agreement between calculated and measured x-ray sensitivity changes. Thus it can be concluded that the trapping of electrons in the bulk of a-Se and their subsequent recombination with x-ray generated free holes is the dominant mechanism for ghosting in a-Se.

alpha-Amino-beta-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1.

A series of alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the alpha-amino group (P(1) position), as well as different groups attached to the sulphone group extending into P(1)'. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000x for a number of analogues.

alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1.

A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable.

Discovery of a novel series of selective MMP inhibitors: identification of the gamma-sulfone-thiols.

We have discovered a new series of potent MMP Inhibitors that are selective for MMP-13 over MMP-1 incorporating a gamma-sulfone thiol.

SC-52151, a novel inhibitor of the human immunodeficiency virus protease.

SC-52151 is a potent, selective, tight-binding human immunodeficiency virus (HIV) protease inhibitor containing the novel (R)-(hydroxyethyl) urea isostere. The mean 50% effective concentration for lymphotropic, monocytotropic strains and field isolates of HIV type 1 (HIV-1), HIV-2, and simian immunodeficiency virus is 26 ng/ml (43 nM). The combination of SC-52151 and nucleoside reverse transcriptase inhibitors synergistically inhibited HIV-1 replication without additive toxicity. An extended postantiviral effect correlates with inhibition of gag and gag-pol polyprotein processing. SC-52151 is highly protein bound ( >90%) in human plasma, and the level of partitioning into erythrocytes is low. Physiological concentrations of alpha-1-acid glycoprotein, but not albumin, substantially affect the antiviral potency of SC-52151. The oral bioavailability of [14C]SC-52151 is 17% when it is administered as an elixir to the rat, dog, or monkey. Oxidation of the t-butyl moiety is the major route of biotransformation, and elimination is mainly by biliary excretion. No toxicologically significant effects have been observed in animals. Pharmacokinetic and metabolism studies in multiple animal species predict 20 to 30% systemic bioavailability, an elimination half-life of 1 to 2 h, and a volume of distribution of greater than 3 liters/kg in humans.

X-ray imaging using amorphous selenium: determination of x-ray sensitivity by pulse height spectroscopy.

There is a renewed interest in the application of photoconductors especially amorphous selenium (a-Se) to x-ray imaging. A new method for evaluating W +/-, the energy absorption necessary to release an electron-hole pair in a-Se is described. All previous methods used for the evaluation of the x-ray sensitivity of a-Se measure a change in surface potential on a charged plate due to irradiation by x rays. This results in a measurement of W +/- and other factors in combination. These factors include the energy absorbed from the spectrum of irradiating x rays and the a-Se layer capacitance. Such indirect methods are prone to error. A direct method for the evaluation of W +/-, which is based on the pulse height spectra resulting from the absorption of individual monoenergetic x-ray photons in a-Se, has been developed.

Wiener noise power spectra of radiological television systems using a digital oscilloscope.

Measurement of spatial noise power spectra from television based radiographic and fluoroscopic systems is essential to the understanding of their operation and optimization. However, conventional methods require acquisition and processing of large numbers of complete images, thus confining such measurements to special applications where accessible frame buffers already exist or elaborately equipped laboratories. We have developed a method which only requires storage of single TV lines or point scans. A digital oscilloscope captures these point scans and a laboratory microcomputer facilitates manipulation of the data to separate out different components of the noise power spectra. The x-ray dependent component of the noise power spectrum so produced is not the ordinary Wiener spectrum. However, it is shown that reconstruction of the full Wiener spectrum from this is possible subject only to the requirement that the x-ray noise spectrum at the output of the imaging system is circularly symmetric.

A light source for testing radiological television cameras.

A light source for testing and setting up radiological television systems has been designed and built using green light emitting diodes and an optical integrating sphere. It is shown to have an optical spectrum similar to the green output phosphors used in x-ray image intensifiers (XRII's). It can be made uniform in intensity across the output port and does not show the small scale granularity characteristic of phosphors. It has a Lambertian angular distribution which, by the addition of neutral density filters, can be made to mimic the angular distribution at the output of an XRII. It can easily and accurately be modulated or switched and a luminance comparable to that of an XRII output phosphor can be achieved.