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.

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.

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.

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.

Kidins220/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems.

Signaling downstream of receptor tyrosine kinases controls cell differentiation and survival. How signals from different receptors are integrated is, however, still poorly understood. In this work, we have identified Kidins220 (Kinase D interacting substrate of 220 kDa)/ARMS (Ankyrin repeat-rich membrane spanning) as a main player in the modulation of neurotrophin and vascular endothelial growth factor (VEGF) signaling in vivo, and a primary determinant for neuronal and cardiovascular development. Kidins220(-/-) embryos die at late stages of gestation, and show extensive cell death in the central and peripheral nervous systems. Primary neurons from Kidins220(-/-) mice exhibit reduced responsiveness to brain-derived neurotrophic factor, in terms of activation of mitogen-activated protein kinase signaling, neurite outgrowth and potentiation of excitatory postsynaptic currents. In addition, mice lacking Kidins220 display striking cardiovascular abnormalities, possibly due to impaired VEGF signaling. In support of this hypothesis, we demonstrate that Kidins220 constitutively interacts with VEGFR2. These findings, together with the data presented in the accompanying paper, indicate that Kidins220 mediates the integration of several growth factor receptor pathways during development, and mediates the activation of distinct downstream cascades according to the location and timing of stimulation.

Clinical dose performance of full field digital mammography in a breast screening programme.

OBJECTIVE: BreastCheck, the Irish Breast Screening Programme, has employed three different models of a full field digital mammography (FFDM) system since its transition to a digital service in 2007. The three models from GE Healthcare, Hologic and Sectra exhibit differences in their design and function, the most significant of which include anode target/filter choice, detector technology and the type of exposure automation. METHODS: The aim of this study was to use the results from a clinical breast dose survey to examine the differences between three different FFDM models in terms of exposure selection, breast mean glandular dose (MGD) and automatic exposure control (AEC) dose contribution. RESULTS: The accuracy of the dose estimation was improved by inclusion of the AEC pre-exposure dose contribution. The photon-counting system demonstrated the lowest average MGD. The GE Healthcare and Hologic flat-panel detector systems demonstrated a small but statistically significant dose difference. The pre-exposure dose contribution did not exceed 13% of the total exposure dose for any system in the survey. A comparison of the system calculated organ dose estimate from each machine with the corresponding MGD calculated from medical physics measurements indicated reasonably accurate organ dose estimates for most systems in the survey. CONCLUSION: The results of this study provide a comprehensive assessment of the breast dose performance of current digital mammography systems in a clinical screening setting.

Comprehensive dose survey of breast screening in Ireland.

The primary purpose of this study was to evaluate the impact of digital mammography screening on breast dose by analysing the results of a patient dose survey of the Irish breast screening programme. Results from the survey were used to determine a dose reference level for the screening programme. Approximately, 100 examinations were acquired for each of the digital mammography systems operational in the screening programme. Each examination consisted of two standard views of each breast. The mean glandular dose for each acquired image was calculated. The dose reference level was established by calculating the 95th percentile of the average mean glandular dose for the average compressed breast thickness of the mediolateral oblique views. The overall average mean glandular dose per examination was 2.72 ± 0.04 mGy. The average compressed breast thickness was 61.4 ± 0.03 mm. The average compression force was 109 ± 7 N. A dose reference level value of 1.75 mGy was established for the screening programme. The results of this clinical dose survey provide a valuable indication of the dose performance of modern full field digital mammographic imaging systems. The results demonstrate clearly the dose benefits of digital mammography. The dose benefit of digital screening was further demonstrated by the establishment of a comparatively lower diagnostic reference level for the screening programme. The comparison of the dose performance of individual X-ray systems with the diagnostic reference level highlights the need for more optimisation within the service.

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.

Cortico-hippocampal hyperexcitability in synapsin I/II/III knockout mice: age-dependency and response to the antiepileptic drug levetiracetam.

Synapsins (SynI, SynII, SynIII) are a multigene family of synaptic vesicle (SV) phosphoproteins implicated in the regulation of synaptic transmission and plasticity. Synapsin I, II, I/II and I/II/III knockout mice are epileptic and SYN1/2 genes have been identified as major epilepsy susceptibility genes in humans. We analyzed cortico-hippocampal epileptiform activity induced by 4-aminopyridine (4AP) in acute slices from presymptomatic (3-weeks-old) and symptomatic (1-year-old) Syn I/II/III triple knockout (TKO) mice and aged-matched triple wild type (TWT) controls and assessed the effect of the SV-targeted antiepileptic drug (AED) levetiracetam (LEV) in reverting the epileptic phenotype. Both fast and slow interictal (I-IC) and ictal (IC) events were observed in both genotypes. The incidence of fast I-IC events was higher in presymptomatic TKO slices, while frequency and latency of I-IC events were similar in both genotypes. The major age and genotype effects were observed in IC activity, that was much more pronounced in 3-weeks-old TKO and persisted with age, while it disappeared from 1-year-old TWT slices. LEV virtually suppressed fast I-IC and IC discharges from 3-weeks-old TWT slices, while it only increased the latency of fast I-IC and IC activity in TKO slices. Analysis of I-IC events in patch-clamped CA1 pyramidal neurons revealed that LEV increased the inhibitory/excitatory ratio of I-IC activity in both genotypes. The lower LEV potency in TKO slices of both ages was associated with a decreased expression of SV2A, a SV protein acting as LEV receptor, in cortex and hippocampus. The results demonstrate that deletion of Syn genes is associated with a higher propensity to 4AP-induced epileptic paroxysms that precedes the onset of epilepsy and consolidates with age. LEV ameliorates such hyper excitability by enhancing the inhibition/excitation ratio, although the effect is hindered in TKO slices which exhibit a concomitant decrease in the levels of the LEV receptor SV2A.

The synapsins: key actors of synapse function and plasticity.

The synapsins are a family of neuronal phosphoproteins evolutionarily conserved in invertebrate and vertebrate organisms. Their best-characterised function is to modulate neurotransmitter release at the pre-synaptic terminal, by reversibly tethering synaptic vesicles (SVs) to the actin cytoskeleton. However, many recent data have suggested novel functions for synapsins in other aspects of the pre-synaptic physiology, such as SV docking, fusion and recycling. Synapsin activity is tightly regulated by several protein kinases and phosphatases, which modulate the association of synapsins to SVs as well as their interaction with actin filaments and other synaptic proteins. In this context, synapsins act as a link between extracellular stimuli and the intracellular signalling events activated upon neuronal stimulation. Genetic manipulation of synapsins in various in vivo models has revealed that, although not essential for the basic development and functioning of neuronal networks, these proteins are extremely important in the fine-tuning of neuronal plasticity, as shown by the epileptic phenotype and behavioural abnormalities characterising mouse lines lacking one or more synapsin isoforms. In this review, we summarise the current knowledge about how the various members of the synapsin family are involved in the modulation of the pre-synaptic physiology. We give a comprehensive description of the molecular basis of synapsin function, as well as an overview of the more recent evidence linking mutations in the synapsin proteins to the onset of severe central nervous system diseases such as epilepsy and schizophrenia.

Investigation of the effect of anode/filter materials on the dose and image quality of a digital mammography system based on an amorphous selenium flat panel detector.

A comparison, in terms of image quality and glandular breast dose, was carried out between two similar digital mammography systems using amorphous selenium flat panel detectors. The two digital mammography systems currently available from Lorad-Hologic were compared. The original system utilises Mo/Mo and Mo/Rh as target/filter combinations, while the new system uses W/Rh and W/Ag. Images of multiple mammography phantoms with simulated compressed breast thicknesses of 4 cm, 5 cm and 6 cm and various glandular tissue equivalency were acquired under different spectral conditions. The contrast of five details, corresponding to five glandular compositions, was calculated and the ratio of the square of the contrast-to-noise ratio to the average glandular dose was used as a figure-of-merit (FOM) to compare results. For each phantom thickness and target/filter combination, there is an optimum voltage that maximises the FOM. Results show that the W/Rh combination is the best choice for all the detection tasks studied, but for thicknesses greater than 6 cm the W/Ag combination would probably be the best choice. In addition, the new system with W filter presents a better optimisation of the automatic exposure control in comparison with the original system with Mo filter.

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).

Low-threshold exocytosis induced by cAMP-recruited CaV3.2 (alpha1H) channels in rat chromaffin cells.

We have studied the functional role of CaV3 channels in triggering fast exocytosis in rat chromaffin cells (RCCs). CaV3 T-type channels were selectively recruited by chronic exposures to cAMP (3 days) via an exchange protein directly activated by cAMP (Epac)-mediated pathway. Here we show that cAMP-treated cells had increased secretory responses, which could be evoked even at very low depolarizations (-50, -40 mV). Potentiation of exocytosis in cAMP-treated cells did not occur in the presence of 50 microM Ni2+, which selectively blocks T-type currents in RCCs. This suggests that the "low-threshold exocytosis" induced by cAMP is due to increased Ca2+ influx through cAMP-recruited T-type channels, rather than to an enhanced secretion downstream of Ca2+ entry, as previously reported for short-term cAMP treatments (20 min). Newly recruited T-type channels increase the fast secretory response at low voltages without altering the size of the immediately releasable pool. They also preserve the Ca2+ dependence of exocytosis, the initial speed of vesicle depletion, and the mean quantal size of single secretory events. All this indicates that cAMP-recruited CaV3 channels enhance the secretory activity of RCCs at low voltages by coupling to the secretory apparatus with a Ca2+ efficacy similar to that of already existing high-threshold Ca2+ channels. Finally, using RT-PCRs we found that the fast inactivating low-threshold Ca2+ current component recruited by cAMP is selectively associated to the alpha1H (CaV3.2) channel isoform.