Ephrin-A5 and EphA5 Interaction Induces Synaptogenesis during Early Hippocampal Development

Synaptogenesis is a fundamental step in neuronal development. For spiny glutamatergic synapses in hippocampus and cortex, synaptogenesis involves adhesion of pre and postsynaptic membranes, delivery and anchorage of pre and postsynaptic structures including scaffolds such as PSD-95 and NMDA and AMPA receptors, which are glutamate-gated ion channels, as well as the morphological maturation of spines. Although electrical activity-dependent mechanisms are established regulators of these processes, the mechanisms that function during early development, prior to the onset of electrical activity, are unclear. The Eph receptors and ephrins provide cell contact-dependent pathways that regulate axonal and dendritic development. Members of the ephrin-A family are glycosyl-phosphatidylinositol-anchored to the cell surface and activate EphA receptors, which are receptor tyrosine kinases.Here we show that ephrin-A5 interaction with the EphA5 receptor following neuron-neuron contact during early development of hippocampus induces a complex program of synaptogenic events, including expression of functional synaptic NMDA receptor-PSD-95 complexes plus morphological spine maturation and the emergence of electrical activity. The program depends upon voltage-sensitive calcium channel Ca2+ fluxes that activate PKA, CaMKII and PI3 kinase, leading to CREB phosphorylation and a synaptogenic program of gene expression. AMPA receptor subunits, their scaffolds and electrical activity are not induced. Strikingly, in contrast to wild type, stimulation of hippocampal slices from P6 EphA5 receptor functional knockout mice yielded no NMDA receptor currents.These studies suggest that ephrin-A5 and EphA5 signals play a necessary, activity-independent role in the initiation of the early phases of synaptogenesis. The coordinated expression of the NMDAR and PSD-95 induced by eprhin-A5 interaction with EphA5 receptors may be the developmental switch that induces expression of AMPAR and their interacting proteins and the transition to activity-dependent synaptic regulation

Adaptive Statistical Iterative Reconstruction (ASIR): Re-defining CT dose reduction strategies

Advances in Technology Poster: P104KEY LEARNING OBJECTIVES: (1) Brief description of ASIR (Adaptive Statistical Iterative Reconstruction) physics. (2) Compare diagnostic quality of CT scan images performed without and with ASIR. (3) Demonstrate various clinical applications of ASIR. DESCRIPTION: Diagnostic x-rays account for the largest artificial source of exposure to ionizing radiation and CT represents the greater proportion. Traditionally, reducing CT dose result in an increase in image noise and a compromise on image quality. ASIR, on the other hand utilizes complex algebraic calculations to lower image noise and CT dose without loss of anatomical detail. ASIR has been shown to reduce CT doses by up to 50%. A study conducted in our institution comparing the Dose Length Products (DLPs) of CT pulmonary angiogram scans performed in the same patients without and with ASIR showed statistically significant reduction in dose of up to 42% without compromising diagnostic accuracy (445.87 vs 257.59). This educational poster provides a brief description of how ASIR works. It also shows the diagnostic quality of images obtained with ASIR by comparing similar images of the same patients without ASIR. Thirdly, the various ways in which ASIR can be utilized will be discussed. CONCLUSION: ASIR effectively lowers CT doses without compromising diagnostic quality. Radiologists need to be conversant with recent developments in CT dose lowering strategies such as ASIR and various ways in which it can be utilized clinically

Radiation-reduction strategies in cardiac computed tomographic angiography

Cardiac E-Poster: P512KEY LEARNING OBJECTIVES: To present an in-depth analysis of dose reduction strategies in patients undergoing cardiac CT angiography (CTA). DESCRIPTION: Cardiac CTA has traditionally been associated with high radiation dose but recent technologies and acquisition techniques have allowed for significant dose reduction. Being one of the leading centres in the UK, we will share our experiences in dose reduction using real examples of diagnostic images diagrams and photographs to explain dose reduction strategies which can be classified as: ECG-linked tube current modulation: • Application of max tube current during mid-diastole (60%-80% of R-R interval). This allows dose reduction by up to 37% (stable heart rate) Prospective axial gating: • The importance of heart rate control and regularity. The merits of aggressive beta-blockade will be discussed • ‘Step and shoot’ technique with advantage of Improved resolution (z-axis) as well as drawback such as risk of step artefacts • The concept of ‘padding’ to allow for patients with tachycardia/unstable heart rate Attenuation-dependent tube modulation: • Recently, there has been a shift to modulating tube voltage (kV) from traditional value of 120kV to closer to the k-edge of iodine (80kV). This has allowed for significant dose reduction with increase in patient contrast but patient selection is important • Recent developments: • Iterative reconstruction • Garnet detector technology • High-pitch spiral acquisition CONCLUSION: Use of various strategies based on the use of new technology combined with patient factors can help in dose reduction during cardiac CTA