Synapsin I Synchronizes GABA Release in Distinct Interneuron Subpopulations.

Neurotransmitters can be released either synchronously or asynchronously with respect to action potential timing. Synapsins (Syns) are a family of synaptic vesicle (SV) phosphoproteins that assist gamma-aminobutyric acid (GABA) release and allow a physiological excitation/inhibition balance. Consistently, deletion of either or both Syn1 and Syn2 genes is epileptogenic. In this work, we have characterized the effect of SynI knockout (KO) in the regulation of GABA release dynamics. Using patch-clamp recordings in hippocampal slices, we demonstrate that the lack of SynI impairs synchronous GABA release via a reduction of the readily releasable SVs and, in parallel, increases asynchronous GABA release. The effects of SynI deletion on synchronous GABA release were occluded by ω-AgatoxinIVA, indicating the involvement of P/Q-type Ca2+channel-expressing neurons. Using in situ hybridization, we show that SynI is more expressed in parvalbumin (PV) interneurons, characterized by synchronous release, than in cholecystokinin or SOM interneurons, characterized by a more asynchronous release. Optogenetic activation of PV and SOM interneurons revealed a specific reduction of synchronous release in PV/SynIKO interneurons associated with an increased asynchronous release in SOM/SynIKO interneurons. The results demonstrate that SynI is differentially expressed in interneuron subpopulations, where it boosts synchronous and limits asynchronous GABA release.

Presynaptic muscarinic receptors reduce synaptic depression and facilitate its recovery at hippocampal GABAergic synapses.

Hippocampal gamma oscillation, involved in cognitive processes, can be induced by muscarinic acetylcholine receptors activation and depends in large part on the activation of γ-aminobutyric acidergic (GABAergic) interneurons. The precise role of the modulatory action of muscarinic receptors on GABAergic transmission still remains unclear due to the great heterogeneity of observed effects. We have examined the presynaptic and postsynaptic mechanisms involved. Methacholine induces a down-regulation of evoked inhibitory postsynaptic currents (eIPSCs) not associated with the change of postsynaptic receptors. The significant decrease in the paired-pulse depression strongly suggested a presynaptic mechanism of action. We have used cumulative amplitude profile analysis to show that the impairment of eIPSCs is not related to a decreased size of the readily releasable pool, but rather depends on the reduced release probability by a down-modulation of voltage-gated calcium channels. The decreased neurotransmitter release probability only partially accounts for the dramatic reduction in the rate of synaptic depression evoked by short- and long-lasting tetanic stimuli. This effect is accompanied by a significant enhancement in the rate of recovery from synaptic depression that demonstrates the reinforcement of the synaptic recycling processes. These results show that muscarinic modulation of hippocampal GABAergic synapses confers a greater resistance to sustain periods of intense synaptic activity in the gamma frequency range.

A statistical alternative to current measures of image quality in digital mammography.

Objective. Mammogram image quality in European breast screening systems is defined by threshold gold thickness (T) assessment of the CDMAM contrast-detail phantom. Previous studies have outlined several limitations of the phantom including expense, number of images required and inter-phantom manufacturing variability. Two alternative approaches to image quality assessment for routine quality control are examined and compared to the CDMAM technique: (i) A detectability index (d') based on a non-prewhitened model observer with an eye filter (NPWE) and(ii) A statistical estimate of contrast based on image noise levels (CSTAT).Approach. Thed' calculation follows a previously published methodology based on the NNPS and contrast, both measured from an image of 5 cm of PMMA containing a 0.2 mm Al target, as well as the MTF measured under standard conditions. For the proposed statistical method, pixels in the centre of the same NNPS image were re-binned into a range of equivalent CDMAM target areas. For any area, the minimum contrast necessary to distinguish a signal from the background,CSTAT, is 3.29σat a 95% level of confidence, whereσis the standard deviation of the background pixels. Theoretical analysis predicts a simple relationships betweenCSTAT,Tandd'. Measured values ofCSTATwere compared toTandd' as a function of air kerma at the detector for ten digital mammography systems from three different manufacturers.Main Results. Theoretical relationships betweenCSTAT,d' andTwere demonstrated. Minimum acceptable image quality performance for 0.10 and 0.25 mm diameter discs, defined by the European Guidelines in terms ofT, are equivalent tod' values of 0.85 and 5.36 and thresholdCSTATvalues of 0.055 and 0.022.Significance. Strong correlations between log(T), log(d') and log(CSTAT) suggest that either alternative approach produces information corresponding to that obtained using the CDMAM.CSTATshould be considered as a simple, objective and cost-effective alternative to routine image quality assessment in mammography.

Presynaptic muscarinic receptor subtypes involved in the enhancement of spontaneous GABAergic postsynaptic currents in hippocampal neurons.

We investigated the effects of muscarinic acetylcholine receptor (mAChR) activation on GABAergic synaptic transmission in rat hippocampal neurons. Current-clamp recordings revealed that methacholine produced membrane depolarization and action potential firing. Methacholine augmented the bicuculline-sensitive and GABA(A) -mediated frequency of spontaneous inhibitory postsynaptic currents (sIPSCs); the action of methacholine had a slow onset and longer duration. The increase in methacholine-evoked sIPSCs was completely inhibited by atropine and was insensitive to glutamatergic receptor blockers. Interestingly, methacholine action was not inhibited by intracellular perfusion with GDP-ß-S, suggesting that muscarinic effects on membrane excitability and sIPSC frequency are mainly presynaptic. McN-A-343 and pirenzepine, selective agonist and antagonist of the m1 mAChR subtype, respectively, neither enhanced sIPSCs nor inhibited the methacholine effect. However, the m3-m5 mAChR antagonist 4-DAMP, and the m2-m4 mAChR antagonist himbacine inhibited the methacholine effect. U73122, an IP(3) production inhibitor, and 2APB, an IP(3) receptor blocker, drastically decreased the methacholine effect. Recording of miniature events revealed that besides the effect exerted by methacholine on membrane firing properties and sIPSC frequency, muscarinic receptors also enhanced the frequency of mIPSCs with no effect on their amplitude, possibly modulating the molecular machinery subserving vesicle docking and fusion and suggesting a tight colocalization at the active zone of the presynaptic terminals. These data strongly suggest that by activating presynaptic m2, m3, m4 and m5 mAChRs, methacholine can increase membrane excitability and enhance efficiency in the GABA release machinery, perhaps through a mechanism involving the release of calcium from the endoplasmic reticulum.

Evaluation of microcalcification contrast in clinical images for digital mammography and synthetic mammography.

PURPOSE: The aim of this work was to compare, in a clinical study, digital mammography and synthetic mammography imaging by evaluating the contrast in microcalcifications of different sizes. METHODS: A retrospective review of microcalcifications from 46 patients was undertaken. A Hologic 3-Dimensions mammography system and a HD Combo protocol was used for simultaneous acquisition of the digital and synthetic images. Microcalcifications were classified in accordance with their size, and patient breast images were classified in accordance with their density as adipose, moderately dense and dense. The contrast of the microcalcifications was measured and the contrast ratio between synthetic and digital images was compared. An additional qualitative assessment of the images was presented to correlate the conspicuity of the microcalcifications with the suppression of the structure noise. RESULTS: Microcalcifications in adipose background always exhibit a comparable or better contrast on synthetic images, regardless their size. For moderately dense background, synthetic images show a better contrast in 91.2 % of cases for small microcalcifications and in 90.9 % of cases for large microcalcifications. For a dense background, better contrast is seen in 89.5 % of cases for small microcalcifications, and in 85.7 % of cases for large microcalcifications. The contrast ratio increases with increasing breast glandularity. The suppression of structure noise also contributes to the enhancement of microcalcifications in the synthetic images. CONCLUSIONS: Synthetic mammography imaging is superior to digital mammography imaging in terms of microcalcification contrast, regardless their size and breast density.

Investigation of detector uniformity issues for Siemens Inspiration systems.

PURPOSE: Detector uniformity is an important parameter in digital mammography to guarantee a level of image quality adequate for early detection of breast cancer. Many problems with digital systems have been determined through the uniformity measurement, primarily as a result of incorrect flat-field calibration and artifacts caused by image receptor defects. The European guidelines suggest a method for the image uniformity assessment based on measurement of Signal-to-Noise ratio (SNR) and Pixel Value (PV) across a uniform image. Nineteen mammography systems from the same manufacturer installed in our organization incorporate an a-Se direct conversion detector. Since their installation, instability and inconsistency of image uniformity has attracted medical physicist attention. A number of different tests have been carried out in order to understand and establish reasons for this instability. METHODS: Three different tests have been performed to evaluate the impact of the heel effect, detector temperature and ghosting on the uniformity images. All the tests are based on the acquisition of uniform images as suggested by the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis. RESULTS: Results show that an increase in detector temperature produces an increase of SNR and decrease of uniformity. A further decrease of uniformity ranging between 20% and 30% is due to the ghosting while a decrease of about 10% is due the heel effect. CONCLUSIONS: X-ray tube, system geometry and detector have an impact on the system uniformity and an understanding of the contribution of each is necessary in order to obtain comparable image quality among all the systems.

A novel method for contrast-to-noise ratio (CNR) evaluation of digital mammography detectors.

The purpose of this study was to test a new, simple method of evaluating the contrast-to-noise ratio (CNR) over the entire image field of a digital detector and to compare different mammography systems. Images were taken under clinical exposure conditions for a range of simulated breast thicknesses using poly(methyl methacrylate) (PMMA). At each PMMA thickness, a second image which included an additional 0.2-mm Al sheet was also acquired. Image processing software was used to calculate the CNR in multiple regions of interest (ROI) covering the entire area of the detector in order to obtain a 'CNR image'. Five detector types were evaluated, two CsI-alphaSi (GE Healthcare) flat panel systems, one alphaSe (Hologic) flat panel system and a two generations of scanning photon counting digital detectors (Sectra). Flat panel detectors exhibit better CNR uniformity compared with the first-generation scanning photon counting detector in terms of mean pixel value variation. However, significant improvement in CNR uniformity was observed for the next-generation scanning detector. The method proposed produces a map of the CNR and a measurement of uniformity throughout the entire image field of the detector. The application of this method enables quality control measurement of individual detectors and a comparison of detectors using different technologies.

Allosteric modulation of alpha 7 nicotinic receptors selectively depolarizes hippocampal interneurons, enhancing spontaneous GABAergic transmission.

The role of postsynaptic nicotinic receptors for acetylcholine (nAChRs) in mediating fast neurotransmission processes in the CNS is controversial. Here we have studied the modulation of synaptic transmission by an agonist (choline) and an allosteric modulator (5-OH-indole) of alpha7 nAChRs in rat hippocampal neuronal cultures. Choline evoked a fast inactivating inward current, causing neuron depolarization and action potential discharge, thereby enhancing the spontaneous postsynaptic current activity (sPSCs). This effect was markedly enhanced when both choline and 5-OH-indole were applied together and was blocked by the selective alpha7 nAChR antagonist methyllycaconitine. This choline action was suppressed by the GABA(A) receptor antagonist bicuculline, while the glutamatergic receptor antagonist kynurenic acid had no effect. Frequency, but not amplitude or area, of both excitatory and inhibitory miniature postsynaptic currents (mEPSCs and mIPSCs) were drastically reduced when Ca(2+) influx was blocked by Cd(2+). Additionally, nAChR activation did not modify the mIPSCs. These data suggest that Ca(2+) influx through the highly Ca(2+)-permeablealpha7 nAChRs was insufficient to directly activate neurotransmitter release, suggesting that a tight colocalization of this receptor with secretory hot spots is unlikely. In a few cases, the activation of alpha7 AChRs led to a suppression of spontaneous synaptic transmission. This effect may be related to the potentiation of GABAergic interneurons that inhibit the spontaneous activity of neurons making synapses with the cell under study. We suggest that GABA release is modulated by alpha7 nAChRs. Thus, selective allosteric modulators of alpha7 nAChRs could have potential therapeutic applications in brain disorders such as epilepsy and schizophrenia and in alterations of cognition and sensory processing.

L-type calcium channels in adrenal chromaffin cells: role in pace-making and secretion.

Voltage-gated L-type (Cav1.2 and Cav1.3) channels are widely expressed in cardiovascular tissues and represent the critical drug-target for the treatment of several cardiovascular diseases. The two isoforms are also abundantly expressed in neuronal and neuroendocrine tissues. In the brain, Cav1.2 and Cav1.3 channels control synaptic plasticity, somatic activity, neuronal differentiation and brain aging. In neuroendocrine cells, they are involved in the genesis of action potential generation, bursting activity and hormone secretion. Recent studies have shown that Cav1.2 and Cav1.3 are also expressed in chromaffin cells but their functional role has not yet been identified despite that L-type channels possess interesting characteristics, which confer them an important role in the control of catecholamine secretion during action potentials stimulation. In intact rat adrenal glands L-type channels are responsible for adrenaline and noradrenaline release following splanchnic nerve stimulation or nicotinic receptor activation. L-type channels can be either up- or down-modulated by membrane autoreceptors following distinct second messenger pathways. L-type channels are tightly coupled to BK channels and activate at relatively low-voltages. In this way they contribute to the action potential hyperpolarization and to the pace-maker current controlling action potential firings. L-type channels are shown also to regulate the fast secretion of the immediate readily releasable pool of vesicles with the same Ca(2+)-efficiency of other voltage-gated Ca(2+) channels. In mouse adrenal slices, repeated action potential-like stimulations drive L-type channels to a state of enhanced stimulus-secretion efficiency regulated by beta-adrenergic receptors. Here we will review all these novel findings and discuss the possible implication for a specific role of L-type channels in the control of chromaffin cells activity.

Quantitative analysis of the effect of energy separation in k-edge digital subtraction imaging.

The aim of the work is to quantitatively compare the effect of the energy separation in the k-edge digital subtraction imaging technique. Images of a custom-made, iodine filled (k-edge = 33.17 keV) test object have been acquired with monochromatic x-ray beams (energy spread <0.1 keV) at the ID17 biomedical beamline of the ESRF. Image acquisition has been performed using two energy separations, namely 0.65 keV (32.85 keV and 33.5 keV, respectively) and 4.4 keV (31.2 keV and 35.6 keV, respectively), using beams of energies on either side of the iodine k-edge. Signal and signal-to-noise ratio (SNR) analysis has been performed as a function of DeltaE and the contrast medium concentrations. The results show that the SNR values measured for DeltaE < 1 keV are only slightly higher than those measured for DeltaE = 4.4 keV. This preliminary study shows that monochromaticity and the energy separation obtained with quasi monochromatic beams from conventional x-ray sources might be suitable for this imaging technique.

Evaluation of the minimum iodine concentration for contrast-enhanced subtraction mammography.

Early manifestation of breast cancer is often very subtle and is displayed in a complex and variable pattern of normal anatomy that may obscure the disease. The use of dual-energy techniques, that can remove the structural noise, and contrast media, that enhance the region surrounding the tumour, could help us to improve the detectability of the lesions. The aim of this work is to investigate the use of an iodine-based contrast medium in mammography with two different double exposure techniques: K-edge subtraction mammography and temporal subtraction mammography. Both techniques have been investigated by using an ideal source, like monochromatic beams produced at a synchrotron radiation facility and a clinical digital mammography system. A dedicated three-component phantom containing cavities filled with different iodine concentrations has been developed and used for measurements. For each technique, information about the minimum iodine concentration, which provides a significant enhancement of the detectability of the pathology by minimizing the risk due to high dose and high concentration of contrast medium, has been obtained. In particular, for cavities of 5 and 8 mm in diameter filled with iodine solutions, the minimum concentration needed to obtain a contrast-to-noise ratio of 5 with a mean glandular dose of 2 mGy has been calculated. The minimum concentrations estimated with monochromatic beams and K-edge subtraction mammography are 0.9 mg ml(-1) and 1.34 mg ml(-1) for the biggest and smallest details, respectively, while for temporal subtraction mammography they are 0.84 mg ml(-1) and 1.31 mg ml(-1). With the conventional clinical system the minimum concentrations for the K-edge subtraction mammography are 4.13 mg ml(-1) (8 mm diameter) and 5.75 mg ml(-1) (5 mm diameter), while for the temporal subtraction mammography they are 1.01 mg ml(-1) (8 mm diameter) and 1.57 mg ml(-1) (5 mm diameter).

Opposite action of beta1- and beta2-adrenergic receptors on Ca(V)1 L-channel current in rat adrenal chromaffin cells.

Voltage-gated Ca(2+) channels of chromaffin cells are modulated by locally released neurotransmitters through autoreceptor-activated G-proteins. Clear evidence exists in favor of a Ca(2+) channel gating inhibition mediated by purinergic, opioidergic, and alpha-adrenergic autoreceptors. Few and contradictory data suggest also a role of beta-adrenergic autoreceptors (beta-ARs), the action of which, however, remains obscure. Here, using patch-perforated recordings, we show that rat chromaffin cells respond to the beta-AR agonist isoprenaline (ISO) by either upmodulating or downmodulating the amplitude of Ca(2+) currents through two distinct modulatory pathways. ISO (1 microm) could cause either fast inhibition (approximately 25%) or slow potentiation (approximately 25%), or a combination of the two actions. Both effects were completely prevented by propranolol. Slow potentiation was more evident in cells pretreated with pertussis toxin (PTX) or when beta(1)-ARs were selectively stimulated with ISO + ICI118,551. Potentiation was absent when the beta(2)-AR-selective agonist zinterol (1 microm), the protein kinase A (PKA) inhibitor H89, or nifedipine was applied, suggesting that potentiation is associated with a PKA-mediated phosphorylation of L-channels (approximately 40% L-current increase) through beta(1)-ARs. The ISO-induced inhibition was fast and reversible, preserved in cell treated with H89, and mimicked by zinterol. The action of zinterol was mostly on L-channels (38% inhibition). Zinterol action preserved the channel activation kinetics, the voltage-dependence of the I-V characteristic, and was removed by PTX, suggesting that beta(2)AR-mediated channel inhibition was mainly voltage independent and coupled to G(i)/G(o)-proteins. Sequential application of zinterol and ISO mimicked the dual action (inhibition/potentiation) of ISO alone. The two kinetically and pharmacologically distinct beta-ARs signaling uncover alternative pathways, which may serve the autocrine control of Ca(2+)-dependent exocytosis and other related functions of rat chromaffin cells.

Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels.

In voltage-dependent ion channels, the gating of the channels is determined by the movement of the voltage sensor. This movement reflects the rearrangement of the protein in response to a voltage stimulus, and it can be thought of as a net displacement of elementary charges (e0) through the membrane (z: effective number of elementary charges). In this paper, we measured z in Shaker IR (inactivation removed) K+ channels, neuronal alpha 1E and alpha 1A, and cardiac alpha 1C Ca2+ channels using two methods: (a) limiting slope analysis of the conductance-voltage relationship and (b) variance analysis, to evaluate the number of active channels in a patch, combined with the measurement of charge movement in the same patch. We found that in Shaker IR K+ channels the two methods agreed with a z congruent to 13. This suggests that all the channels that gate can open and that all the measured charge is coupled to pore opening in a strictly sequential kinetic model. For all Ca2+ channels the limiting slope method gave consistent results regardless of the presence or type of beta subunit tested (z = 8.6). However, as seen with alpha 1E, the variance analysis gave different results depending on the beta subunit used. alpha 1E and alpha 1E beta 1a gave higher z values (z = 14.77 and z = 15.13 respectively) than alpha 1E beta 2a (z = 9.50, which is similar to the limiting slope results). Both the beta 1a and beta 2a subunits, coexpressed with alpha 1E Ca2+ channels facilitated channel opening by shifting the activation curve to more negative potentials, but only the beta 2a subunit increased the maximum open probability. The higher z using variance analysis in alpha 1E and alpha 1E beta 1a can be explained by a set of charges not coupled to pore opening. This set of charges moves in transitions leading to nulls thus not contributing to the ionic current fluctuations but eliciting gating currents. Coexpression of the beta 2a subunit would minimize the fraction of nulls leading to the correct estimation of the number of channels and z.

A prototype of a quasi-monochromatic system for mammography applications.

Improvement in image contrast and dose reduction, in mammographic x-ray imaging, can be achieved using narrow energy band x-ray beams in the 16-24 keV range. As part of an Italian Government funded project, a quasi-monochromatic system for mammography applications has been developed. The system is based on a tunable narrow energy band x-ray source operating in the 16-24 keV energy range. The bremsstrahlung beam is monochromatized via Bragg diffraction by a highly oriented pyrolytic graphite mosaic crystal (HOPG). The scanning system provides a large field (18 x 24 cm2) of quasi-monochromatic x-rays with energy resolution ranging from 10% at 18 keV to 17.2% at 24 keV. The system has been characterized in terms of fluence rate and energy resolution. An x-ray tube developed ad hoc allows us to acquire images in a reasonable time to minimize the motion blur. A qualitative analysis has been performed in order to know if the prototype system performances are far from a clinical application, by evaluating the spatial resolution, the field uniformity and the image quality as a function of the quasi-monochromatic beam energy. Dose evaluation has been performed as a function of the energy and compared to a conventional system for mammography. The quasi-monochromatic prototype system can produce comparable image quality at half the dose.

Modulation by extracellular pH of the activity of GABAA receptors on rat cerebellum granule cells.

The Cl- currents activated by GABA via GABAA receptors in rat cerebellum granule cells in culture were studied by whole-cell patch-clamp. These currents were measured at various extracellular pH. The currents activated by 100 microM GABA, both the peak and the steady-state component, increase at acidic pH's and decrease at basic pH's. The transition point being at around 7.7. Interestingly, passing from pH 7.4 to 6.4 the GABA dose-response curve indicates that the increases in the peak current are related to an augmented maximal current. The increases in the steady-state component are mainly due to a higher affinity of the receptors for the neurotransmitter and disappear at saturating [GABA]. The study of the I-V curves for the GABA activated peak Cl- currents at pH 6.4, 7.4 and 8.4 reveals linearity in the latter instance. However, an outward rectification is present at the two more acidic pH's. This fact suggests that the protonation of basic amino acids at the acid pH does involve rectification of Cl- channel conductance. Overall, the data indicate that slight changes in in situ extracellular pH may have profound influences on GABAA receptor function.

Quasi-monochromatic x-rays for diagnostic radiology.

Monochromatic x-ray beams are desirable in various fields of diagnostic radiology; in fact a reduction of the dose and an enhancement of the contrast could be achieved. In this work two different methods to monochromatize x-ray beams produced by conventional tubes have been compared. In the first one the beam is obtained via Bragg diffraction on mosaic crystal and in the second one by attenuating the polychromatic beam with aluminium filters. We have simulated quasi-monochromatic x-ray spectra by setting suitable values of Bragg's angle to obtain beams tuned to 20, 30, 40 and 50 keV with the SHADOW code, an x-ray tracing program designed to study the propagation and the interaction of a photon beam through an optical system. We have validated such a program by comparing some calculated data with measurements carried out on an experimental apparatus. Attenuated polychromatic x-ray spectra have been simulated by setting appropriate values of aluminium filters and potential with the SPECTRUM PROCESSOR, the software version of the Catalogue of Spectral Data for Diagnostic X-Rays, which provides radiographic x-ray spectra that can be attenuated with several material filters. The relation between the energy resolution and the flux as a function of the mean energy has been investigated and results have been compared. Results show that quasi-monochromatic x-ray beams produced via Bragg diffraction exhibit, for a given mean energy and energy resolution, a higher total flux compared to attenuated spectra.

Dose comparison between conventional and quasi-monochromatic systems for diagnostic radiology.

Several techniques have been introduced in the last year to reduce the dose to the patient by minimizing the risk of tumour induced by radiation. In this work the radiological potential of dose reduction in quasi-monochromatic spectra produced via mosaic crystal Bragg diffraction has been evaluated, and a comparison with conventional spectra has been performed for four standard examinations: head, chest, abdomen and lumbar sacral spine. We have simulated quasi-monochromatic x-rays with the Shadow code, and conventional spectra with the Spectrum Processor. By means of the PCXMC software, we have simulated four examinations according to parameters established by the European Guidelines, and calculated absorbed dose for principal organs and the effective dose. Simulations of quasi-monochromatic laminar beams have been performed without anti-scatter grid, because of their inherent scatter geometry, and compared with simulations with conventional beams with anti-scatter grids. Results have shown that the dose reduction due to the introduction of quasi-monochromatic x-rays depends on different parameters related to the quality of the beam, the organ composition and the anti-scatter grid. With parameters chosen in this study a significant dose reduction can be achieved for two out of four kinds of examination.

Dual-energy imaging in full-field digital mammography: a phantom study.

A dual-energy technique which employs the basis decomposition method is being investigated for application to digital mammography. A three-component phantom, made up of plexiglas, polyethylene, and water, was doubly exposed with the full-field digital mammography system manufactured by General Electric. The 'low' and 'high' energy images were recorded with a Mo/Mo anode-filter combination and a Rh/Rh combination, respectively. The total dose was kept within the acceptable levels of conventional mammography. The first hybrid images obtained with the dual-energy algorithm are presented in comparison with a conventional radiograph of the phantom. Image-quality characteristics at contrast cancellation angles between plexiglas and water are discussed. Preliminary results show that a combination of a standard Mo-anode 28 kV radiograph with a Rh-anode 49 kV radiograph provides the best compromise between image-quality and dose in the hybrid image.

Criteria and suspension levels in diagnostic radiology.

The EC (European Council) Directive on radiation protection of patients requires that criteria for acceptability of equipment in diagnostic radiology, nuclear medicine and radiotherapy be established throughout the member states. This study reviews the background to this requirement and to its implementation in practice. It notes and considers parallel requirements in the EC medical devices directive and International Electrotechnical Commission standards that it is also important to consider and that both sets of requirements should ideally be harmonised due to the global nature of the equipment industry. The study further reviews the types of criteria that can be well applied for the above purposes, and defines qualitative criteria and suspension levels suitable for application. Both are defined and relationships with other acceptance processes are considered (including acceptance testing at the time of purchase, commissioning and the issue of second-hand equipment). Suspension levels are divided into four types, A, B, C and D, depending on the quality of evidence and consensus they are based on. Exceptional situations involving, for example, new or rapidly evolving technology are also considered. The publication and paper focuses on the role of the holder of the equipment and related staff, particularly the medical physics expert and the practitioner. Advice on how the criteria should be created and implemented is provided for these groups and how this might be coordinated with the supplier. Additional advice on the role of the regulator is provided.

Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays.

Multielectrode arrays (MEAs) are extensively used for electrophysiological studies on brain slices, but the spatial resolution and field of recording of conventional arrays are limited by the low number of electrodes available. Here, we present a large-scale array recording simultaneously from 4096 electrodes used to study propagating spontaneous and evoked network activity in acute murine cortico-hippocampal brain slices at unprecedented spatial and temporal resolution. We demonstrate that multiple chemically induced epileptiform episodes in the mouse cortex and hippocampus can be classified according to their spatio-temporal dynamics. Additionally, the large-scale and high-density features of our recording system enable the topological localization and quantification of the effects of antiepileptic drugs in local neuronal microcircuits, based on the distinct field potential propagation patterns. This novel high-resolution approach paves the way to detailed electrophysiological studies in brain circuits spanning spatial scales from single neurons up to the entire slice network.