Leveraging multi-layer imager detector design to improve low-dose performance for megavoltage cone-beam computed tomography.

While megavoltage cone-beam computed tomography (CBCT) using an electronic portal imaging device (EPID) provides many advantages over kilovoltage (kV) CBCT, clinical adoption is limited by its high doses. Multi-layer imager (MLI) EPIDs increase DQE(0) while maintaining high resolution. However, even well-designed, high-performance MLIs suffer from increased electronic noise from each readout, degrading low-dose image quality. To improve low-dose performance, shift-and-bin addition (ShiBA) imaging is proposed, leveraging the unique architecture of the MLI. ShiBA combines hardware readout-binning and super-resolution concepts, reducing electronic noise while maintaining native image sampling. The imaging performance of full-resolution (FR); standard, aligned binned (BIN); and ShiBA images in terms of noise power spectrum (NPS), electronic NPS, modulation transfer function (MTF), and the ideal observer signal-to-noise ratio (SNR)-the detectability index (d')-are compared. The FR 4-layer readout of the prototype MLI exhibits an electronic NPS magnitude 6-times higher than a state-of-the-art single layer (SLI) EPID. Although the MLI is built on the same readout platform as the SLI, with each layer exhibiting equivalent electronic noise, the multi-stage readout of the MLI results in electronic noise 50% higher than simple summation. Electronic noise is mitigated in both BIN and ShiBA imaging, reducing its total by ~12 times. ShiBA further reduces the NPS, effectively upsampling the image, resulting in a multiplication by a sinc2 function. Normalized NPS show that neither ShiBA nor BIN otherwise affects image noise. The LSF shows that ShiBA removes the pixilation artifact of BIN images and mitigates the effect of detector shift, but does not quantifiably improve the MTF. ShiBA provides a pre-sampled representation of the images, mitigating phase dependence. Hardware binning strategies lower the quantum noise floor, with 2  ×  2 implementation reducing the dose at which DQE(0) degrades by 10% from 0.01 MU to 0.004 MU, representing 20% improvement in d'

Implementation of 3 T Lactate-Edited 3D 1H MR Spectroscopic Imaging with Flyback Echo-Planar Readout for Gliomas Patients

The purpose of this study was to implement a new lactate-edited 3D 1H magnetic resonance spectroscopic imaging (MRSI) sequence at 3 T and demonstrate the feasibility of using this sequence for measuring lactate in patients with gliomas. A 3D PRESS MRSI sequence incorporating shortened, high bandwidth 180° pulses, new dual BASING lactate-editing pulses, high bandwidth very selective suppression (VSS) pulses and a flyback echo-planar readout was implemented at 3 T. Over-prescription factor of PRESS voxels was optimized using phantom to minimize chemical shift artifacts. The lactate-edited flyback sequence was compared with lactate-edited MRSI using conventional elliptical k-space sampling in a phantom and volunteers, and then applied to patients with gliomas. The results demonstrated the feasibility of detecting lactate within a short scan time of 9.5 min in both phantoms and patients. Over-prescription of voxels gave less chemical shift artifacts allowing detection of lactate on the majority of the selected volume. The normalized SNR of brain metabolites using the flyback encoding were comparable to the SNR of brain metabolites using conventional phase encoding MRSI. The specialized lactate-edited 3D MRSI sequence was able to detect lactate in brain tumor patients at 3 T. The implementation of this technique means that brain lactate can be evaluated in a routine clinical setting to study its potential as a marker for prognosis and response to therapy

Zinc Coordination Is Required for and Regulates Transcription Activation by Epstein-Barr Nuclear Antigen 1

Epstein-Barr Nuclear Antigen 1 (EBNA1) is essential for Epstein-Barr virus to immortalize naïve B-cells. Upon binding a cluster of 20 cognate binding-sites termed the family of repeats, EBNA1 transactivates promoters for EBV genes that are required for immortalization. A small domain, termed UR1, that is 25 amino-acids in length, has been identified previously as essential for EBNA1 to activate transcription. In this study, we have elucidated how UR1 contributes to EBNA1's ability to transactivate. We show that zinc is necessary for EBNA1 to activate transcription, and that UR1 coordinates zinc through a pair of essential cysteines contained within it. UR1 dimerizes upon coordinating zinc, indicating that EBNA1 contains a second dimerization interface in its amino-terminus. There is a strong correlation between UR1-mediated dimerization and EBNA1's ability to transactivate cooperatively. Point mutants of EBNA1 that disrupt zinc coordination also prevent self-association, and do not activate transcription cooperatively. Further, we demonstrate that UR1 acts as a molecular sensor that regulates the ability of EBNA1 to activate transcription in response to changes in redox and oxygen partial pressure (pO2). Mild oxidative stress mimicking such environmental changes decreases EBNA1-dependent transcription in a lymphoblastoid cell-line. Coincident with a reduction in EBNA1-dependent transcription, reductions are observed in EBNA2 and LMP1 protein levels. Although these changes do not affect LCL survival, treated cells accumulate in G0/G1. These findings are discussed in the context of EBV latency in body compartments that differ strikingly in their pO2 and redox potential

A Prototype Table-Top Inverse-Geometry Volumetric CT System

A table-top volumetric CT system has been implemented that is able to image a 5-cm-thick volume in one circular scan with no cone-beam artifacts. The prototype inverse-geometry CT (IGCT) scanner consists of a large-area, scanned x-ray source and a detector array that is smaller in the transverse direction. The IGCT geometry provides sufficient volumetric sampling because the source and detector have the same axial, or slice direction, extent. This paper describes the implementation of the table-top IGCT scanner, which is based on the NexRay Scanning-Beam Digital X-ray system (NexRay, Inc., Los Gatos, CA) and an investigation of the system performance. The alignment and flat-field calibration procedures are described, along with a summary of the reconstruction algorithm. The resolution and noise performance of the prototype IGCT system are studied through experiments and further supported by analytical predictions and simulations. To study the presence of cone-beam artifacts, a “Defrise” phantom was scanned on both the prototype IGCT scanner and a micro CT system with a ±5° cone angle for a 4.5-cm volume thickness. Images of inner ear specimens are presented and compared to those from clinical CT systems. Results showed that the prototype IGCT system has a 0.25-mm isotropic resolution and that noise comparable to that from a clinical scanner with equivalent spatial resolution is achievable. The measured MTF and noise values agreed reasonably well with theoretical predictions and computer simulations. The IGCT system was able to faithfully reconstruct the laminated pattern of the Defrise phantom while the micro CT system suffered severe cone-beam artifacts for the same object. The inner ear acquisition verified that the IGCT system can image a complex anatomical object, and the resulting images exhibited more high-resolution details than the clinical CT acquisition. Overall, the successful implementation of the prototype system supports the IGCT concept for single-rotation volumetric scanning free from cone-beam artifacts

Leveraging multi-layer imager detector design to improve low-dose performance for megavoltage cone-beam computed tomography

While megavoltage cone-beam computed tomography (CBCT) using an electronic portal imaging device (EPID) provides many advantages over kilovoltage (kV) CBCT, clinical adoption is limited by its high doses. Multi-layer imager (MLI) EPIDs increase DQE(0) while maintaining high resolution. However, even well-designed, high-performance MLIs suffer from increased electronic noise from each readout, degrading low-dose image quality. To improve low-dose performance, shift-and-bin addition (ShiBA) imaging is proposed, leveraging the unique architecture of the MLI. ShiBA combines hardware readout-binning and super-resolution concepts, reducing electronic noise while maintaining native image sampling. The imaging performance of full-resolution (FR); standard, aligned binned (BIN); and ShiBA images in terms of noise power spectrum (NPS), electronic NPS, modulation transfer function (MTF), and the ideal observer signal-to-noise ratio (SNR)-the detectability index (d')-are compared. The FR 4-layer readout of the prototype MLI exhibits an electronic NPS magnitude 6-times higher than a state-of-the-art single layer (SLI) EPID. Although the MLI is built on the same readout platform as the SLI, with each layer exhibiting equivalent electronic noise, the multi-stage readout of the MLI results in electronic noise 50% higher than simple summation. Electronic noise is mitigated in both BIN and ShiBA imaging, reducing its total by ~12 times. ShiBA further reduces the NPS, effectively upsampling the image, resulting in a multiplication by a sinc2 function. Normalized NPS show that neither ShiBA nor BIN otherwise affects image noise. The LSF shows that ShiBA removes the pixilation artifact of BIN images and mitigates the effect of detector shift, but does not quantifiably improve the MTF. ShiBA provides a pre-sampled representation of the images, mitigating phase dependence. Hardware binning strategies lower the quantum noise floor, with 2  ×  2 implementation reducing the dose at which DQE(0) degrades by 10% from 0.01 MU to 0.004 MU, representing 20% improvement in d'

Dimensions of Diversity in Spatial Cognition: Culture, Context, Age, and Ability

Throughout the lifespan and across cultures, all human behavior happens in space. By early childhood, people are capable of navigating complex 3D environments, executing sophisticated motor plans, and coordinating action with others. They also use their representations of space to structure a variety of non-spatial concepts, including time, number, similarity, and emotion. How do people perform these cognitive feats? One source of insight comes from studying the diversity of spatial cognition: Although the physical properties of space are invariant, the way people typically conceptualize space varies radically across groups, between individuals, and over development. By studying this variation in spatial cognition, we can better understand the universal set of cognitive and neural mechanisms that underlie it, with implications for the cognitive sciences, education, and design