Defectos paradójicos en regiones con necrosis miocárdica. análisis mediante gated-spect de perfusión miocárdica.

Objectius: Valorar el significat dels defectes paradoxals (DP) segmentaris (captació en esforç més gran que en repòs) a la gated-SPECT (Single Photon Emission Computer Tomography) de perfusió miocàrdica amb compostos tecneciats en regions amb necrosi miocàrdica. Material i mètodes: Es van revisar 1764 SPECT de perfusió miocàrdica estrès-repòs consecutives de pacients amb infart (IM) previ i es van identificar 117 pacients (6,6%) en els quals els DPs corresponien a una regió amb necrosi miocàrdica. Es van valorar els criteris gammagràfics de viabilitat (intensitat del defecte, valor d'aquesta intensitat ponderat pel nombre de segments compromesos-VIP-, la motilitat i l'engrossiment miocàrdic sistòlic) en els segments d'aquestes regions i les característiques de l'artèria responsable en els 96 pacients en els quals s'havia practicat una coronariografia. Resultats: Es van analitzar 160 necrosis, 125 (75%) paradoxals (67 (54%) en regió AnteroSeptoApical i 58 (46%) en regió InferoLateral) i 35 (25%) no paradoxals (19 (54%) ASA i 16 ( 46%) IL). Els valors de severitat de la necrosi i del VIP van ser inferiors en l'estudi d'estrès respecte al repòs i la diferència d'aquests va ser sempre negativa, evidenciant un comportament gammagràfic paradoxal. Per contra, aquests valors van ser inferiors al repòs respecte a l'estrès en les necrosi no paradoxals posant de manifest un comportament gammagràfic de mínima o nul reversibilitat. Així mateix, es van trobar alteracions lleus en la motilitat i engrossiment de les necrosi paradoxals i moderats en les necrosi no paradoxals. Es van trobar 102 necrosis amb DP i coronariografia dels quals, 84 (88%) tenien permeabilitat a l'artèria responsable de la necrosi i 12 pacients (12%) tenien circulació colateral per compensar l'oclusió de l'artèria responsable. Conclusions: Tots els segments amb DP en regions amb necrosi complien criteris gammagràfics de viabilitat en les imatges d'estrès, considerant aquestes imatges millors per a l'avaluació d'aquest tipus de lesions. El vas responsable de la regió amb DP es trobava permeable o bé presentava circulació colateral evident en els casos en què la coronària es trobava closa.

A gated single-photon avalanche diode array fabricated in a conventional CMOS process for triggered systems

A bidimensional array based on single-photon avalanche diodes for triggered imaging systems is presented. The diodes are operated in the gated mode of acquisition to reduce the probability to detect noise counts interfering with photon arrival events. In addition, low reverse bias overvoltages are used to lessen the dark count rate. Experimental results demonstrate that the prototype fabricated with a standard HV-CMOS process gets rid of afterpulses and offers a reduced dark count probability by applying the proposed modes of operation. The detector exhibits a dynamic range of 15 bits with short gated"on" periods of 10ns and a reverse bias overvoltage of 1.0V.

Low noise pixel detectors based on gated geiger mode avalanche photodiodes

The gated operation is proposed as an effective method to reduce the noise in pixel detectors based on Geiger mode avalanche photodiodes. A prototype with the sensor and the front-end electronics monolithically integrated has been fabricated with a conventional HV-CMOS process. Experimental results demonstrate the increase of the dynamic range of the sensor by applying this technique.

Gated Geiger mode avalanche photodiode pixels with integrated readout electronics for low noise photon detection

Avalanche photodiodes operated in the Geiger mode offer a high intrinsic gain as well as an excellent timing accuracy. These qualities make the sensor specially suitable for those applications where detectors with high sensitivity and low timing uncertainty are required. Moreover, they are compatible with standard CMOS technologies, allowing sensor and front-end electronics integration within the pixel cell. However, the sensor suffers from high levels of intrinsic noise, which may lead to erroneous results and limit the range of detectable signals. They also increase the amount of data that has to be stored. In this work, we present a pixel based on a Geiger-mode avalanche photodiode operated in the gated mode to reduce the probability to detect noise counts interfering with photon arrival events. The readout circuit is based on a two grounds scheme to enable low reverse bias overvoltages and consequently lessen the dark count rate. Experimental characterization of the fabricated pixel with the HV-AMS 0.35µm standard technology is also presented in this article.

A unique role for Kv3 voltage-gated potassium channels in starburst amacrine cell signaling in mouse retina

Direction-selective retinal ganglion cells show an increased activity evoked by light stimuli moving in the preferred direction. This selectivity is governed by direction-selective inhibition from starburst amacrine cells occurring during stimulus movement in the opposite or null direction. To understand the intrinsic membrane properties of starburst cells responsible for direction-selective GABA release, we performed whole-cell recordings from starburst cells in mouse retina. Voltage-clamp recordings revealed prominent voltage-dependent K+ currents. The currents were mostly blocked by 1 mm TEA, activated rapidly at voltages more positive than -20 mV, and deactivated quickly, properties reminiscent of the currents carried by the Kv3 subfamily of K+ channels. Immunoblots confirmed the presence of Kv3.1 and Kv3.2 proteins in retina and immunohistochemistry revealed their expression in starburst cell somata and dendrites. The Kv3-like current in starburst cells was absent in Kv3.1-Kv3.2 knock-out mice. Current-clamp recordings showed that the fast activation of the Kv3 channels provides a voltage-dependent shunt that limits depolarization of the soma to potentials more positive than -20 mV. This provides a mechanism likely to contribute to the electrical isolation of individual starburst cell dendrites, a property thought essential for direction selectivity. This function of Kv3 channels differs from that in other neurons where they facilitate high-frequency repetitive firing. Moreover, we found a gradient in the intensity of Kv3.1b immunolabeling favoring proximal regions of starburst cells. We hypothesize that this Kv3 channel gradient contributes to the preference for centrifugal signal flow in dendrites underlying direction-selective GABA release from starburst amacrine cells.

Dynamic range extension of SiPM detectors with the time-gated operation

The silicon photomultiplier (SiPM) is a novel detector technology that has undergone a fast development in the last few years, owing to its single-photon resolution and ultra-fast response time. However, the typical high dark count rates of the sensor may prevent the detection of low intensity radiation fluxes. In this article, the time-gated operation with short active periods in the nanosecond range is proposed as a solution to reduce the number of cells fired due to noise and thus increase the dynamic range. The technique is aimed at application fields that function under a trigger command, such as gated fluorescence lifetime imaging microscopy.

Dynamic model of the left ventricle for use in simulation of myocardial perfusion SPECT and gated SPECT

Simulation is a useful tool in cardiac SPECT to assess quantification algorithms. However, simple equation-based models are limited in their ability to simulate realistic heart motion and perfusion. We present a numerical dynamic model of the left ventricle, which allows us to simulate normal and anomalous cardiac cycles, as well as perfusion defects. Bicubic splines were fitted to a number of control points to represent endocardial and epicardial surfaces of the left ventricle. A transformation from each point on the surface to a template of activity was made to represent the myocardial perfusion. Geometry-based and patient-based simulations were performed to illustrate this model. Geometry-based simulations modeled ~1! a normal patient, ~2! a well-perfused patient with abnormal regional function, ~3! an ischaemic patient with abnormal regional function, and ~4! a patient study including tracer kinetics. Patient-based simulation consisted of a left ventricle including a realistic shape and motion obtained from a magnetic resonance study. We conclude that this model has the potential to study the influence of several physical parameters and the left ventricle contraction in myocardial perfusion SPECT and gated-SPECT studies.

Dynamic range extension of SiPM detectors with the time-gated operation

The silicon photomultiplier (SiPM) is a novel detector technology that has undergone a fast development in the last few years, owing to its single-photon resolution and ultra-fast response time. However, the typical high dark count rates of the sensor may prevent the detection of low intensity radiation fluxes. In this article, the time-gated operation with short active periods in the nanosecond range is proposed as a solution to reduce the number of cells fired due to noise and thus increase the dynamic range. The technique is aimed at application fields that function under a trigger command, such as gated fluorescence lifetime imaging microscopy.

The L-type voltage-gated calcium channel modulates microglial pro-inflammatory activity

Under pathological conditions, microglia, the resident CNS immune cells, become reactive and release pro-inflammatory cytokines and neurotoxic factors. We investigated whether this phenotypic switch includes changes in the expression of the L-type voltage-gated calcium channel (VGCC) in a rat model of N-methyl-d-aspartate-induced hippocampal neurodegeneration. Double immunohistochemistry and confocal microscopy evidenced that activated microglia express the L-type VGCC. We then analyzed whether BV2 microglia express functional L-type VGCC, and investigated the latter's role in microglial cytokine release and phagocytic capacity. Activated BV2 microglia express the CaV1.2 and CaV1.3 subunits of the L-type VGCC determined by reverse transcription-polymerase chain reaction, Western blot and immunocytochemistry. Depolarization with KCl induced a Ca2+ entry facilitated by Bay k8644 and partially blocked with nifedipine, which also reduced TNF-α and NO release by 40%. However, no nifedipine effect on BV2 microglia viability or phagocytic capacity was observed. Our results suggest that in CNS inflammatory processes, the L-type VGCC plays a specific role in the control of microglial secretory activity.

Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins

Voltage-gated K+ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to −10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 −/− mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

K(+) channel expression distinguishes subpopulations of parvalbumin- and somatostatin-containing neocortical interneurons

Kv3.1 and Kv3.2 K+ channel proteins form similar voltage-gated K+ channels with unusual properties, including fast activation at voltages positive to −10 mV and very fast deactivation rates. These properties are thought to facilitate sustained high-frequency firing. Kv3.1 subunits are specifically found in fast-spiking, parvalbumin (PV)-containing cortical interneurons, and recent studies have provided support for a crucial role in the generation of the fast-spiking phenotype. Kv3.2 mRNAs are also found in a small subset of neocortical neurons, although the distribution of these neurons is different. We raised antibodies directed against Kv3.2 proteins and used dual-labeling methods to identify the neocortical neurons expressing Kv3.2 proteins and to determine their subcellular localization. Kv3.2 proteins are prominently expressed in patches in somatic and proximal dendritic membrane as well as in axons and presynaptic terminals of GABAergic interneurons. Kv3.2 subunits are found in all PV-containing neurons in deep cortical layers where they probably form heteromultimeric channels with Kv3.1 subunits. In contrast, in superficial layer PV-positive neurons Kv3.2 immunoreactivity is low, but Kv3.1 is still prominently expressed. Because Kv3.1 and Kv3.2 channels are differentially modulated by protein kinases, these results raise the possibility that the fast-spiking properties of superficial- and deep-layer PV neurons are differentially regulated by neuromodulators. Interestingly, Kv3.2 but not Kv3.1 proteins are also prominent in a subset of seemingly non-fast-spiking, somatostatin- and calbindin-containing interneurons, suggesting that the Kv3.1–Kv3.2 current type can have functions other than facilitating high-frequency firing.

Avoiding sensor blindness in Geiger mode avalanche photodiode arrays fabricated in a conventional CMOS process

The need to move forward in the knowledge of the subatomic world has stimulated the development of new particle colliders. However, the objectives of the next generation of colliders sets unprecedented challenges to the detector performance. The purpose of this contribution is to present a bidimensional array based on avalanche photodiodes operated in the Geiger mode to track high energy particles in future linear colliders. The bidimensional array can function in a gated mode to reduce the probability to detect noise counts interfering with real events. Low reverse overvoltages are used to lessen the dark count rate. Experimental results demonstrate that the prototype fabricated with a standard HV-CMOS process presents an increased efficiency and avoids sensor blindness by applying the proposed techniques.

Los espacios residenciales de tipo privativo y la construcción de la nueva ciudad: visiones de privatopía

La proliferación de los desarrollos residenciales con acceso restringido y de tipo privativo (condominios, supermanzanas, countries, barrios cerrados, etc.) se presentan en el texto como reflejo, a la vez que resultado, de los nuevos procesos de urbanización. Las características de estos desarrollos reflejan los cambios más generales que se van produciendo en el espacio urbano: la privatización, la fragmentación y la tematización, entendida ésta como la construcción de espacios de simulación. A través del análisis bibliográfico, y de la reflexión sobre unos casos de estudio en la región metropolitana de Nueva York, el trabajo incide sobre las causas (el neoliberalismo, los patrones de consumo global) y las consecuencias de la proliferación de los espacios residenciales de tipo privativo: la fragmentación urbana, la privatización y la introducción de nuevos patrones de segregación.

Ras-association domain of sorting nexin 27 is critical for regulating expression of GIRK potassium channels

G protein-gated inwardly rectifying potassium (GIRK) channels play an important role in regulating neuronal excitability. Sorting nexin 27b (SNX27b), which reduces surface expression of GIRK channels through a PDZ domain interaction, contains a putative Ras-association (RA) domain with unknown function. Deleting the RA domain in SNX27b (SNX27b-DRA) prevents the down-regulation of GIRK2c/GIRK3 channels. Similarly, a point mutation (K305A) in the RA domain disrupts regulation of GIRK2c/GIRK3 channels and reduces H-Ras binding in vitro. Finally, the dominant-negative H-Ras (S17N) occludes the SNX27b-dependent decrease in surface expression of GIRK2c/GIRK3 channels. Thus, the presence of a functional RA domain and the interaction with Ras-like G proteins comprise a novel mechanism for modulating SNX27b control of GIRK channel surface expression and cellular excitability.

Readout schemes for low noise single-photon avalanche diodes fabricated in conventional HV-CMOS technologies

Three different pixels based on single-photon avalanche diodes for triggered applications, such as fluorescence lifetime measurements and high energy physics experiments, are presented. Each pixel consists of a 20µm x 100µm (width x length) single photon avalanche diode and a monolithically integrated readout circuit. The sensors are operated in the gated mode of acquisition to reduce the probability to detect noise counts interferring with real radiation events. Each pixel includes a different readout circuit that allows to use low reverse bias overvoltages. Experimental results demonstrate that the three pixels present a similar behaviour. The pixels get rid of afterpulses and present a reduced dark count probability by applying the gated operation. Noise figures are further improved by using low reverse bias overvoltages. The detectors exhibit an input dynamic range of 13.35 bits with short gated"on" periods of 10ns and a reverse bias overvoltage of 0.5V. The three pixels have been fabricated in a standard HV-CMOS process.